CROSS REFERENCE TO RELATED APPLICATIONS 0001 This application is a continuation-in-part of U.S. patent application Ser. No. 09/129,360, filed Aug. 5, 1998, pending.

TECHNICAL FIELD 0002 This invention relates to compounds having activity to inhibit matrix metalloproteinases, to pharmaceutical compositions comprising these compounds and to a medical method of treatment. More particularly, this invention concerns reverse hydroxamate-containing compounds which inhibit matrix metalloproteinases, pharmaceutical compositions comprising these compounds and a method of inhibiting matrix metalloproteinases.

BACKGROUND OF THE INVENTION 0003 The matrix metalloproteinases (MMP's) are a class of extracellular enzymes including collagenase, stromelysin and gelatinase which are believed to be involved in the tissue destruction which accompanies a large number of disease states varying from arthritis to cancer. 0004 Typical connective tissue cells are embedded within an extracellular matrix of high molecular weight proteins and glycoproteins. In healthy tissue, there is a continual and delicately-balanced series of processes which include cell division, matrix synthesis and matrix degradation. In certain pathological conditions, an imbalance of these three processes can lead to improper tissue restructuring. In arthritis, for example, joint mobility can be lost when there is improper remodelling of load-bearing joint cartilage. With cancer, lack of coordination of cell division and the two processes of matrix synthesis and degradation may lead to conversion of transformed cells to invasive phenotypes in which increased matrix turnover permits tumor cells to penetrate basement membranes surrounding capillaries which, in turn, may lead to subsequent metastasis. 0005 There has been hightened interest in discovering therapeutic agents which bind to and inhibit MMP's. The discovery of new therapeutic agents possessing this activity will lead to new drugs having a novel mechanism of action for combating disease states involving tissue degenerative processes including, for example, rheumatoid arthritis, osteoarthritis, osteopenias such as osteoporosis, periodontitis, gingivitis, corneal, epidermal or gastric ulceration, and tumor growth and metastasis or invasion.

SUMMARY OF THE INVENTION 0006 In its principle embodiment, the present invention provides a matrix metalloproteinase inhibitory compound of formula (I), 2

0007 or a pharmaceutically acceptable salt or prodrug thereof, wherein 0008 n is zero; 0009 R1 and R3 are independently selected from the group consisting of 0010 (1) hydrogen and 0011 (2) alkyl of one to six carbon atoms; 0012 R2 and R4 are independently selected from the group consisting of 0013 (1) hydrogen, 0014 (2) alkyl of one to six carbon atoms, 0015 (3) alkenyl of one to six carbon atoms, 0016 (4) alkynyl of one to six carbon atoms, 0017 (5) alkoxyalkyl, wherein the alkyl and the alkyl part of the alkoxy are independently of one to six carbon atoms, 0018 (6) alkoxycarbonylalkyl, wherein the alkylene and alkyl groups are independently of one to six carbon atoms, 0019 (7) haloalkyl of one to six carbon atoms, 0020 (8) hydroxyalkyl, wherein the alkylene group is of one to six carbon atoms, 0021 (9) -(alkylene)-S(O)p-alkyl, wherein the alkylene is of one to six carbon atoms, p is zero to two, and the alkyl is is of one to six carbon atoms, 0022 (10) phenyl, 0023 (11) phenylalkoxyalkyl, wherein the alkylene and alkyl groups are independently of one to six carbon atoms, 0024 (12) phenylalkyl, wherein the alkylene group is of one to six carbon atoms, 0025 (13) phenoxyalkyl, wherein the alkylene group is of one to six carbon atoms, 0026 (14) -(alkylene)-N(R5)SO2-phenyl, wherein the alkylene is of one to six carbon atoms, and wherein R5 is selected from the group consisting of 0027 (a) hydrogen and 0028 (b) alkyl of one to six carbon atoms, 0029 (15) (heterocycle)oxyalkyl, wherein the alkylene group is of one to six carbon atoms, 0030 (16) -(alkylene)-S(O)p-heterocycle, wherein the alkylene group is of one to six carbon atoms, 0031 (17) -(alkylene)-heterocycle, wherein the alkylene group is of one to six carbon atoms, 0032 (18) -(alkylene)-NR6R7, wherein the alkylene group is of one to six carbon atoms, 0033 (19) -heterocycle, and 0034 (20) -cycloalkyl, 0035 wherein for (1 5)-(17) and (19), the heterocycle is selected from the group consisting of 0036 (a) pyridyl, 0037 (b) pyrazinyl, 0038 (c) pyridazinyl, 0039 (d) furyl, 0040 (e) thienyl, 0041 (f) isoxazolyl, 0042 (g) oxazolyl, 0043 (h) thiazolyl, 0044 (i) isothiazolyl, 3

0045 wherein for (10)-(17) and (19), the phenyl, the phenyl parts of phenylalkoxyalkyl, phenylalkyl, -(alkylene)-N(R5)SO2-phenyl, phenoxyalkyl, and -(alkylene)-S(O)p-phenyl, and the heterocycle, the heterocycle parts of (heterocycle)oxyalkyl, -(alkylene)-heterocycle and -(alkylene)-S(O)p-heterocycle are optionally substituted with one, two, or three substituents independently selected from the group consisting of 0046 (a) alkyl of one to six carbon atoms, 0047 (b) alkoxy of one to six carbon atoms, 0048 (c) alkoxyalkyl, wherein the alkyl group and the alkylene group are independently of one to six carbon atoms, 0049 (d) halo, 0050 (e) haloalkyl of one to six carbon atoms, 0051 (f) hydroxy, 0052 (g) hydroxyalkyl of one to six carbon atoms, 0053 (h) -(alkylene)-heterocycle, wherein the alkylene group is of one to six carbon atoms, 0054 (i) -(alkylene)-phenyl, wherein the alkylene group is of one to six carbon atoms, 0055 (j) N(R5)SO2-alkyl, wherein the alkyl group is of one to six carbon atoms, 0056 (k) phenyl, wherein the phenyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of 0057 (i) cyano, 0058 (ii) nitro, and 0059 (iii) halo, 0060 (l) C(O)OR5, and 0061 (m) C(O)NRxRy, wherein Rx and Ry are independently selected from the group consisting of 0062 (i) alkyl of one to six carbon atoms, 0063 (ii) phenyl, and 0064 (iii) phenylalkyl, wherein the alkyl group is of one to six carbon atoms, wherein for (ii) and (iii), the phenyl and the phenyl part of phenylalkyl are optionally substituted with substituents independently selected from the group consisting of halo and alkoxy of one to six carbon atoms, and 0065 wherein for (18), R6 and R7 are independently selected from the group consisting of 0066 (a) hydrogen, 0067 (b) alkyl of one to six carbon atoms, 0068 (c) cycloalkyl of three to eight carbon atoms, 0069 (d) cycloalkylalkyl, wherein the cycloalkyl group is of three to eight carbon atoms, and the alkylene group is of one to ten carbon atoms, 0070 (e) alkanoyl of one to ten carbon atoms, 0071 (f) phenyl, and 0072 (g) phenylalkyl, wherein the alkylene group is of three to ten carbon atoms, 0073 wherein for (f) and (g), the phenyl and the phenyl part of phenylalkyl are optionally substituted with one or two substituents independently selected from the group consisting of 0074 (i) alkyl of one to six carbon atoms, 0075 (ii) alkoxy of one to six carbon atoms, 0076 (iii) perfluoroalkyl of one to six carbon atoms, 0077 (iv) halo, 0078 (v) haloalkyl of one to six carbon atoms, and 0079 (vi) alkanoyl of one to six carbon atoms, or 0080 R6 and R7, taken together with the nitrogen atom to which they are attached, define a group selected from the group consisting of 0081 (1) morpholinyl, 0082 (2) thiomorpholinyl, 0083 (3) thiomorpholinyl sulfone, 0084 (4) pyrrolidinyl, 0085 (5) piperazinyl, 0086 (6) piperidinyl, 0087 (7) succinimidyl, 0088 (8) maleimidyl, 0089 (9) glutarimidyl, 0090 (10) phthalimidyl, 0091 (11) naphthalimidyl, 4

0092 wherein for (1)-(23), the groups defined by R6 and R7, together with the nitrogen atom to which they are attached, are optionally substituted with one or two substituents independently selected from the group consisting of 0093 (a) halo, 0094 (b) alkyl of one to six carbon atoms, 0095 (c) alkoxy, wherein the alkyl part of the alkoxy is of one to six carbon atoms, 0096 (d) phenoxy, 0097 (e) phenylalkyl, wherein the alkyl group is of one to six carbon atoms, and 0098 (f) benzyloxy; or 0099 R1 and R2, taken together with the carbon atom to which they are attached form a ring selected from the group consisting of 0100 (1) spiroalkyl of three to eight carbon atoms and 0101 (2) tetrahydropyranyl; or 0102 R3 and R4, taken together with the carbon atom to which they are attached, form a spiroalkyl group of three to eight carbon atoms; or 0103 R1 and R3 taken together with the carbon atoms to which they are attached are a 5, 6, or 7-membered carbocyclic ring; 0104 X is selected from the group consisting of 0105 (1) O, 0106 (2) NR5SO2, 0107 (3) S(O)p, and 0108 (4) C(O), 0109 wherein each group is drawn with its left-hand end being the end which attaches to the alkylene group and its right-hand end being the end which attaches to Ar1; 0110 Ar1 is phenyl which is optionally substituted with one or two substituents independently selected from the group consisting of 0111 (a) alkyl of one to six carbon atoms, 0112 (b) perfluoroalkyl of one to six carbon atoms, 0113 (c) halo, 0114 (d) haloalkyl of one to six carbon atoms, 0115 (e) alkoxy of one to six carbon atoms, 0116 (f) hydroxy, 0117 (g) hydroxyalkyl of one to six carbon atoms, 0118 (h) alkoxyalkyl, wherein the alkyl and alkylene groups are independently of one to six carbon atoms, and 0119 (i) nitro; 0120 Y is selected from the group consisting of 0121 (1) a covalent bond, 0122 (2) O, 0123 (3) alkylene of two to four carbon atoms, 0124 (4) piperidineneyl, 0125 (5) alkenylene of two carbon atoms, 0126 (6) alkynylene of two carbon atoms, 0127 (7) S(O)p, and 0128 (8) C(O); and 0129 Ar2 is an aryl group selected from the group consisting of 0130 (1) phenyl, 0131 (2) pyridyl, 0132 (3) pyrazinyl, 0133 (4) pyridazinyl, 0134 (5) furyl, 0135 (6) thienyl, 0136 (7) isoxazolyl, 0137 (8) oxazolyl, 0138 (9) thiazolyl, and 0139 (10) isothiazolyl, 0140 wherein the aryl group is optionally substituted with one, two, or three substituents independently selected from the group consisting of 0141 (a) alkyl of one to six carbon atoms, 0142 (b) alkoxy of one to six carbon atoms, 0143 (c) alkoxy of one to six carbon atoms substituted with alkoxy of one to six carbon atoms, 0144 (d) -alkyl-CO2R5, 0145 (e) -alkyl-NRxRy, 0146 (f) alkoxyalkyl, wherein the alkyl group is of one to six carbon atoms, and the alkylene group is of one to six carbon atoms, 0147 (g) cyano, 0148 (h) cyanoalkyl of one to six carbon atoms, 0149 (i) halo, 0150 (j) haloalkyl of one to six carbon atoms, 0151 (k) hydroxy, 0152 (l) hydroxyalkyl of one to six carbon atoms, 0153 (m) hydroxyalkyl, wherein the alkyl group is of one to six carbon atoms, 0154 (n) thioalkoxy of one to six carbon atoms, 0155 (o) thioalkoxyalkyl, wherein the alkyl group is of one to six carbon atoms, and the alkylene group is of one to six carbon atoms, 0156 (p) phenylalkoxy, wherein the alkylene group is of one to six carbon atoms, 0157 (q) phenoxy, 0158 (r) phenoxyalkyl, wherein the alkylene group is of one to six carbon atoms, 0159 (s) (heterocycle)oxy, 0160 (t) (heterocycle)oxyalkyl, wherein the alkylene group is of one to six carbon atoms, 0161 (u) perfluoroalkyl of one to six carbon atoms, 0162 (v) perfluoroalkoxy, wherein the perfluoroalkyl part is of one to six carbon atoms, 0163 (w) sulfinylalkyl, wherein the alkyl part is of one to six carbon atoms, 0164 (x) sulfonylalkyl, wherein the alkyl part is of one to six carbon atoms, 5

0165 wherein X is selected from the group consisting of CH2, CH2O and O, and Y is selected from the group consisting of C(O) and (C(R)2)v, where R is hydrogen or alkyl of one to four carbon atoms, and v is 1-3, 0166 (z) N(R5)SO2R5, wherein R5 is defined previously and R5 is selected from the group consisting of 0167 (i) hydrogen and 0168 (ii) alkyl of one to six carbon atoms, and 0169 (aa) SO2N(R5)(R5), 0170 wherein for (s) and (t), the heterocycle part of (heterocycle)oxy, and (heterocycle)oxyalkyl are selected from the group consisting of 0171 (i) pyridyl, 0172 (ii) pyrazinyl, 0173 (iii) pyridazinyl, 0174 (iv) furyl, 0175 (v) thienyl, 0176 (vi) isoxazolyl, 0177 (vii) oxazolyl, 0178 (viii) thiazloyl, and 0179 (ix) isothiazolyl, and 0180 wherein for (s) and (t), the heterocycle part of (heterocycle)oxy and (heterocycle)oxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of 0181 (i) alkyl of one to six carbon atoms, 0182 (ii) alkoxy of one to six carbon atoms, 0183 (iii) perfluoroalkyl of one to six carbon atoms, 0184 (iv) halo, 0185 (v) cyano, 0186 (vi) cyanoalkyl, wherein the alkyl is of one to six carbon atoms, 0187 (vii) haloalkyl of one to six carbon atoms, and 0188 (viii) alkanoyl of one to six carbon atoms, and 0189 wherein for (q) and (r), the phenyl part of phenoxy and phenoxyalkyl are optionally substituted with one or two substituents independently selected from the group consisting of 0190 (i) alkyl of one to six carbon atoms, 0191 (ii) alkoxy of one to six carbon atoms, 0192 (iii) perfluoroalkyl of one to six carbon atoms, 0193 (iv) halo, 0194 (v) cyano, 0195 (vi) cyanoalkyl, wherein the alkyl is of one to six carbon atoms, 0196 (vii) haloalkyl of one to six carbon atoms, and 0197 (viii) alkanoyl of one to six carbon atoms. 0198 In another embodiment, the present invention provides pharmaceutical compositions which comprise a therapeutically effective amount of compound of formula I in combination with a pharmaceutically acceptable carrier. 0199 In yet another embodiment, the present invention provides a method of inhibiting matrix metalloproteinases in a host mammal in need of such treatment comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION

Definition Of Terms 0200 As used throughout this specification and the appended claims, the following terms have the meanings specified: 0201 The term alkyl, as used herein, represents a monovalent group derived from a straight or branched chain saturated hydrocarbon by the removal of a single hydrogen atom and is exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, neopentyl, and the like. The alkyl groups of this invention can be optionally substituted. 0202 The term alkanoyl, as used herein, represents an alkyl group, as defined above, attached to the parent molecular group through a carbonyl group and is exemplified by formyl, acetyl, propionyl, butanoyl, and the like. The alkanoyl groups of this invention can be optionally substituted. 0203 The term alkenyl, as used herein, represents monovalent straight or branched chain groups containing a carbon-carbon double bond derived from an alkene by the removal of one hydrogen atom and is exemplified by ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like. The alkenyl groups of this invention can be optionally substituted. 0204 The term alkoxy, as used herein, represents an alkyl group attached to the parent molecular group through an oxygen atom. The alkyl part of the alkoxy group can be substituted with additional alkoxy groups. Alkoxy groups are exemplified by methoxy, isopropoxy, tert-butoxy, 2-methoxyethoxy, and the like. The alkoxy groups of this invention can be optionally substituted. 0205 The term alkoxyalkyl as used herein, represents an alkyl group to which is attached an alkoxy group. The alkoxyalkyl groups of this invention can be optionally substituted. 0206 The term alkoxycarbonyl, as used herein, represents an ester group, i.e. an alkoxy group attached to the parent molecular group through a carbonyl group, and is exemplified by methoxycarbonyl, ethoxycarbonyl, and the like. The alkoxycarbonyl groups of this invention can be optionally substituted. 0207 The term alkoxycarbonylalkyl, as used herein, represents an alkyl group, as defined above, substituted by a alkoxycarbonyl group. The alkoxycarbonylalkyl groups of this invention can be optionally substituted. 0208 The term alkylene, as used herein, represents a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms and is exemplified by methyene, ethylene, isopropylene, and the like. The alkylene groups of this invention can be optionally substituted. 0209 The term alkynyl, as used herein, represents represents monovalent straight or branched chain groups of two to six carbon atoms containing a carbon-carbon triple bond derived from an alkyne by the removal of one hydrogen atom and is exemplified by ethynyl, 1-propynyl, and the like. The alkynyl groups of this invention can be optionally substituted. 0210 The term benzyloxy, as used herein, represents phenyl-(CH2)O. The benzyloxy groups of this invention can be optionally substituted. 0211 The term cyano, as used herein, represents a CN group. 0212 The term cyanoalkyl, as used herein, represents a cyano group attached to the parent molecular moiety through an alkyl group. The cyanoalkyl groups of this invention can be optionally substituted. 0213 The term cycloalkyl, as used herein represents a monovalent saturated cyclic hydrocarbon group and is exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo2.2.1heptyl, and the like. The cycloalkyl groups of this invention can be optionally substituted. 0214 The term cycloalkylalkyl, as used herein, represents a cycloalkyl group attached to the parent molecular group through an alkylene group. The cycloalkylalkyl groups of this invention can be optionally substituted. 0215 The term halo, as used herein, represents F, Cl, Br, and I. 0216 The term haloalkyl, as used herein, represents an alkyl group substituted by one, two, three or four halogen atoms and is exemplified by chloromethyl, bromoethyl, chlorodifluoromethyl, and the like. The haloalkyl groups of this invention can be optionally substituted. 0217 The term heterocycle, as used herein, represents a five-, six- or seven-membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. The five-membered ring has zero to two double bonds and the six- and seven-membered rings have zero to three double bonds. Hererocycles include indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofiryl, benzothienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiomorpholino sulfone, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, pyrimidyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, dihydroindolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, pyranyl, dihydropyranyl, dithiazolyl, benzofuranyl, benzothienyl, succinimidyl, maleimidyl, glutarimidyl, phthalimidyl, naphthalimidyl, and the like. The heterocycle groups of this invention can be optionally substituted. 0218 Heterocycles also include 6

0219 wherein X is selected from CH2, CH2O and O, and Y is selected from C(O) and (C(R)2)v, where R is hydrogen or alkyl of one to four carbons, and v is 1-3. 0220 The term (heterocycle)oxy, as used herein, represents a heterocycle group attached to the parent molecular moiety through oxygen. The (heterocycle)oxy groups of this invention can be optionally substituted. 0221 The term (heterocycle)oxyalkyl, as used herein, represents a (heterocycle)oxy group attached to the parent molecular group through an alkyl group. The (heterocycle)oxyalkyl groups of this invention can be optionally substituted. 0222 The term hydroxy as used herein, represents an OH group. 0223 The term hydroxyalkyl, as used herein, represents an alkyl group, as defined above, substituted by one to three hydroxy groups, with the proviso that no more than one hydroxy group may be attached to a single carbon atom of the alkyl group and is exemplified by hydroxymethyl, dihydroxypropyl, and the like. The hydroxyalkyl groups of this invention can be optionally substituted. 0224 The term nitro, as used herein, refers to NO2. 0225 The term perfluoroalkyl, as used herein, represents an alkyl group, as defined herein, wherein each hydrogen radical bound to the alkyl group has been replaced by a fluoride radical. Perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl, and the like. The perfluoroalkyl groups of this invention can be optionally substituted. 0226 The term perfluoroalkoxy, as used herein, refers to a perfluoroalkyl group, as defined herein, attached to the parent molecular group through an oxygen atom. The perfluoroalkoxy groups of this invention can be optionally substituted. 0227 The term pharmaceutically acceptable salt, as use herein, represents those salts which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M Berge, et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66:1-19. The salts can be prepared in situ during the final isolation and purification of the compounds of the invention or separately by reacting the free base group with a suitable organic acid. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphersulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like. 0228 The term phenoxy, as used herein, represents a phenyl group attached to the parent molecular group through an oxygen atom. The phenoxy groups of this invention can be optionally substituted. 0229 The term phenoxyalkyl, as used herein, represents a phenoxy group attached to the parent molecular group through an alkyl group. The phenoxyalkyl groups of this invention can be optionally substituted. 0230 The term phenyl, as used herein, represents a 6-membered, monocyclic, aromatic carbocyclic ring. The phenyl groups of this invention can be optionally substituted. 0231 The term phenylalkyl, as used herein, represents an phenyl group attached to the parent molecular group through an alkylene group and is exemplified by benzyl, phenethyl, and the like. The phenylalkyl groups of this invention can be optionally substituted. 0232 The term phenylalkoxy, as used herein, represents a phenyl group attached to the parent molecular group through an alkoxy group. The phenylalkoxy groups of this invention can be optionally substituted. 0233 The term phenylalkoxyalkyl as used herein, represents a phenylalkoxy group, as defined above, attached to the parent molecular group through an alkyl group. The phenylalkoxyalkyl groups of this invention can be optionally substituted. 0234 The term piperidineneyl, as used herein, represents a divalent group derived from piperidine by the removal of two hydrogen atoms. The piperidineneyl groups of this invention can be optionally substituted. 0235 The term prodrug, as used herein, represents compounds which are rapidly transformed in vivo to the parent compound of the above formula, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference. Prodrugs of the compounds of the present invention are, within the scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. 0236 The term spiroalkyl, as used herein, represents an alkylene diradical, both ends of which are bonded to the same carbon atom of the parent group to form a spirocyclic group. The spiroalkyl groups of this invention can be optionally substituted. 0237 The term sulfinyl, as used herein, refers to an S(O) group. 0238 The term sulfinylalkyl, as used herein, refers to an alkyl group, as defined herein, attached to the parent mplecular group through a sulfinyl group. 0239 The term sulfonyl, as used herein, refers to an SO2 group. 0240 The term sulfonylalkyl, as used herein, refers to an alkyl group, as defined herein, attached to the parent mplecular group through a sulfonyl group. The sulfonylalkyl groups of this invention can be optionally substituted. 0241 The term thioalkoxy, as used herein, represents represents an alkyl group attached to the parent molecular group through a sulfur atom. The thioalkoxy groups of this invention can be optionally substituted. 0242 Compounds of the present invention may exist as stereoisomers, wherein asymmetric or chiral centers are present. These compounds are designated by the symbols R or S, depending on the configuration of subsitiuents around the chiral carbon atom. The present invention contemplates various stereoisomers and mixtures thereof. Stereoisomers include enantiomers and diastereomers, and mixtures of enantiomers or diastereomers are designated (). Individual stereoisomers of compounds of the present invention may be prepared synthetically from commercially available starting materials which contain asymmetric or chiral centers or by preparation of racemic mixtures followed by resolution well-known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary or (2) direct separation of the mixture of optical enantiomers on chiral chromatographic columns.

PREFERRED EMBODIMENTS 0243 Preferred compounds of the present invention have formula (I), wherein 0244 R1, R3 and R4 are H; 0245 X is selected from the group consisting of 0246 (1) O, 0247 (2) C(O), 0248 (3) S(O)p, wherein p is 2, and 0249 (4) NR5SO2; 0250 Ar1 is phenyl; 0251 Y is selected from the group consisting of a 0252 (1) covalent bond and 0253 (2) O; and 0254 n is zero; 0255 More preferred compounds of the present invention have formula (I), wherein 0256 R1, R3 and R4 are H; 0257 X is O and S(O)p; 0258 Ar1 is phenyl; 0259 Y is a covalent bond; and 0260 n is zero. 0261 Preferred compounds falling within the scope of formula (I) include but are not limited to: 0262 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-phenoxyethyl-N-hydroxyformamide; 0263 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(phenylthio)ethyl-N-hydroxyformamide; 0264 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)ethyl-N-hydroxyformamide; 0265 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)ethyl-N-hydroxyformamide; 0266 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)propyl-N-hydroxyformamide; 0267 ()-N-1-3-(cyanomethyl)-1,1-biphenyl-4-yloxymethylpentyl-N-hydroxyformamide; 0268 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-3-methylbutyl-N-hydroxyformamide; 0269 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-methylbutyl-N-hydroxyformamide; 0270 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethylpentyl-N-hydroxyformamide; 0271 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(4-methylphenyl)ethyl-N-hydroxyformamide; 0272 ()-N-2-(4-cyano-1,1-biphenyl-4-yl)oxy-1-(4-fluorophenyl)ethyl-N-hydroxyformamide; 0273 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(4-fluorophenyl)ethyl-N-hydroxyformamide; 0274 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethylethyl-N-hydroxyformamide; 0275 ()-N-2-(4-cyano-1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0276 ()-N-1-4-(2E-phenylethenyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0277 ()-N-1-4-(2-furanyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0278 ()-N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0279 ()-N-1-(4-fluoro1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0280 ()-N-1-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0281 ()-N-1-(4-methoxy1,1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0282 ()-N-1-(4-methyl1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0283 ()-N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0284 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-ethoxy 1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0285 ()-N-1-4-(1,3-benzodioxol-5-yl)phenoxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0286 ()-N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyfonnamide; 0287 ()-N-1-4-(3-thienyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0288 ()-N-1-(1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyfonnamide; 0289 ()-N-1-(3-chloro-4-fluoro1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0290 ()-N-1-(2-methyl1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0291 ()-N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0292 ()-N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)ethyl-N-hydroxyformamide; 0293 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0294 ()-N-1-4-(4-phenyl-1-piperidinyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0295 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0296 ()-N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-methyl(4-methylphenyl)sulfonylaminoethyl-N-hydroxyformamide; 0297 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-4,4-dimethyl-2,5-dioxo-3-(3-pyridinylmethyl)-1-imidazolidinylethyl-N-hydroxyformamide; 0298 ()-N-2-(4-cyano 1,1-biphenyl-4-yl)oxy-1-methylpropyl-N-hydroxyformamide; 0299 ()-N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0300 ()-N-1-4-(methylthio) 1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0301 ()-N-1-4-4-(trifluoromethyl)phenoxyphenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0302 ()-N-1-4-(trifluoromethoxy)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-2-N-hydroxyformamide; 0303 ()-N-1-4-(methylsulfonyl)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0304 ()-N-1-3-(cyanomethyll)-4-methoxyl1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0305 ()-N-1-3-(cyanomethyl)1,1-biphenyl-4-yloxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0306 ()-N-1-(4-butoxy1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0307 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0308 ()-N-1-4-(methylsulfonyll)1,1-biphenyl-4-yloxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyfonnamide; 0309 ()-N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide; 0310 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethyl-2,6-dioxo-1-piperidinyl)ethyl-N-hydroxyformamide; 0311 ()-N-1S-(4-cyano 1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide; 0312 ()-N-1R-(4-cyano1,1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide; 0313 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-3-methyl-2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide; 0314 N-4-4-(4-chlorophenoxy)phenylsulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide; 0315 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2-methoxycarbonyl)-phenylthioethyl-N-hydroxyformamide; 0316 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-5-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxypentyl-N-hydroxyformamide; 0317 ()-N-1-(4-cyano 1,1-biphenyl-4-yl)oxymethyl-4-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxybutyl-N-hydroxyformamide; 0318 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-4-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxybutyl-N-hydroxyformamide; 0319 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-5-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxypentyl-N-hydroxyformamide; 0320 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(5,5-dimethyl-2,4-dioxo-3-oxazolidinyl)ethyl-N-hydroxyformamide; 0321 ()-N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0322 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3-methyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0323 ()-N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0324 ()-N-1-(4-chloro-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0325 ()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0326 ()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-isopropylthioethyl-N-hydroxyformamide; 0327 ()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0328 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0329 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-benzyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0330 ()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0331 ()-N-1-4-methoxy1,1-biphenyl-4-yl)sulfonylmethylethyl-N-hydroxyformamide; 0332 ()-N-1-(4-chloro1,1-biphenyl-4-yl)sulfonylmethylethyl-N-hydroxyformamide; 0333 ()-N-1-4-(1,3-benzodioxol-5-yl)phenylsulfonylmethylethyl-N-hydroxyformamide; 0334 ()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethylethyl-N-hydroxyformamide; 0335 ()-N-1-(4-methoxy1,1-biphenyl-4-yl)sulfonylmethylpropyl-N-hydroxyformamide; 0336 ()-N-1-1,1-dimethyl-2-(4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0337 ()-N-1-(phenylmethoxy)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0338 ()-N-1-(hydroxymethyl)-2-(4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0339 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylthioethyl-N-hydroxyformamide; 0340 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0341 ()-N-1-(2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0342 ()-N-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0343 ()-N-1-(4-butyl1,1-biphenyl-4-yl)oxymethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0344 ()-N-1-(3-methy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0345 N-4-4-(4-chloro1,1-biphenyl-4-yl)sulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide; 0346 ()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0347 ()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0348 ()-N-1-(4-butyl1,1-biphenyl-4-yl)sulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0349 ()-N-1-(4-butyl1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0350 ()-N-1-3-(cyanomethyl)1,1-biphenyl-4-yloxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0351 ()-N-1-4-(2-thienyl)phenoxymethyl-2-1-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0352 ()-N-1-(3-nitro1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0353 ()-N-1-(4-methyl1,1-biphenyl-4-yl)oxymethyl-2-3-(methylsulfonyl)-aminophenylethyl-N-hydroxyformamide; 0354 ()-N-1-3-(diethylamino)carbonylphenylmethyl-2-(4-methyl1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0355 ()-N-1-(4-cyano1,1,1-biphenyl-4-yl)oxymethyl-2-(4-cyano 1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0356 ()-N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0357 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(2-methoxyethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0358 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-propoxy1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0359 ()-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-pentyloxy 1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide; 0360 ()-N-1-3-(cyanomethyl)1,1-biphenyl-4-ylsulfonylmethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0361 ()-N-1-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0362 ()-N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0363 ()-N-1-3-(cyanomethyl)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0364 ()-N-1-(4-cyano 1,1-biphenyl-4-yl)oxylmethyl-2-(1,6-dihydro-3-methyl-6-oxo-1-pyridazinyl)ethyl-N-hydroxyformamide; 0365 ()-N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0366 ()-N-1-4-(4-fluorophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0367 ()-N-1-4-(4-pyridinyl)phenoxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0368 (S)-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0369 (R)-N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy) 1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0370 N-1-4-(trifluoromethoxy))1,1-biphenyl-4-yloxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0371 N-1-4-(4-pyridinylthio)phenoxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0372 N-1-(4-chlorophenoxy)phenylsulfonylmethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0373 N-1-(4-cyano1,1-biphenyl-4-yl)oxylmethyl-2-(1,6-dihydro-6-oxo-1-pyridazinyl)ethyl-N-hydroxyformamide; 0374 N-1-4-(aminosulfonyl)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0375 N-1-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0376 N-1-4-(4-pyridinyloxy)phenylsulfonylethyl-N-hydroxyformamide; 0377 N-1-(4-cyanophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0378 N-1-4-4-(trifluoromethoxy)phenoxyphenylsulfonylmethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide; 0379 N-1-4-4-(trifluoromethoxy)phenoxyphenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0380 ()-N-hydroxy-N-1-(3-pyridinyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-yl-sulfonylethylformamide;()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(4-chlorophenoxy)phenylsulfonyl-ethylformamide; 0381 ()-N-hydroxy-N-1-methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-ethylformamide; 0382 ()-N-hydroxy-N-1-(2-pyridinyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-yl-sulfonylethylformamide; 0383 ()-N-1-(4,4-dimethyl-2,6-dioxo-1-piperidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0384 ()-N-hydroxy-N-3-hydroxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-methylpropylformamide; 0385 ()-N-hydroxy-N-1-(methoxymethyl)-2-4-(trifluoromethyl) 1,1-biphenyl-4-ylsulfonylethylformamide; 0386 ()-N-1-(1,3-benzodioxol-5-yl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-ethyl-N-hydroxyformamide; 0387 ()-N-hydroxy-N-4-hydroxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-methylbutylformamide; 0388 ()-N-hydroxy-N-1-4-(methoxymethoxy)phenyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide; 0389 ()-N-hydroxy-N-1-(1-methyl-1H-pyrrol-2-yl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0390 ()-N-hydroxy-N-1-phenyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonyl-ethylformamide; 0391 ()-N-hydroxy-N-1-(2-thienyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonyl-ethylformamide; 0392 ()-N-1-(2-furanyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0393 ()-N-1-(5,5-dimethyl-2,4-dioxo-3-oxazolidinyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide; 0394 ()-N-hydroxy-N-1-(methoxymethyl)-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethylformamide; 0395 ()-N-hydroxy-N-1-(phenylmethoxy)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethylformamide; 0396 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethylformamide; 0397 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethylformamide; 0398 S-(R*,S*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0399 S-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0400 S-(R*,R*)-N-hydroxy-N-(2,3-dihydroxy)-1-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylmethylpropyl-N-hydroxyformamide; 0401 ()-N-1-(dimethylamino)methyl-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethyl-N-hydroxyformamide; 0402 S-(R*,R*)-N-2-(4-chloro1,1-biphenyl-4-yl)sulfonyl-1-(2,2-dimethyl-1,3-dioxol-4-yl)ethyl-N-hydroxyformamide; 0403 ()-N-1-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide; 0404 R-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0405 R-(S*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0406 S-(R*,R*)-N-1-(2,2-diethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethyl-N-hydroxyformamide; 0407 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylsulfonyl)1,1-biphenyl-4-ylsulfonylethylformamide; 0408 ()-N-1-4-(1,3-benzodioxol-5-yl)phenylsulfonylmethyl-2-hydroxyethyl-N-hydroxyformamide; 0409 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylthio)1,1-biphenyl-4-yl-sulfonylethylformamide; 0410 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethylformamide; 0411 ()-N-hydroxy-N-1-(hydroxymethyl)-2-(4chloro 1,1-biphenyl-4-yl)sulfonyl-ethylformamide; 0412 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoromethyl)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0413 ()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylsulfonyl)phenoxyphenyl-sulfonylethylfornamide; 0414 ()-N-1-methyl-3-(4-chloro1,1-biphenyl-4-yl)-3-oxopropyl-N-hydroxy-formamide; 0415 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-butylphenoxy)-phenylsulfonylethyl-N-hydroxyformamide; 0416 ()-N-3-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)-1-4-4-(trifluoromethyl)phenoxyphenylsulfonylmethylpropyl-N-hydroxyformamide; 0417 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0418 ()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-3-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methylpropyl-N-hydroxyformamide; 0419 ()-N-2-4-(4-cyano1,1-biphenyl-4-yl)oxycyclohexyl-N-hydroxyformamide; 0420 ()-N-2-4-4-(trifluoromethoxy) 1,1-biphenyl-4-yl)oxycyclohexyl-N-hydroxyformamide; 0421 ()-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3-methyl-6-oxo-1 (6H)-pyridazinyl)ethyl-N-hydroxyformamide; 0422 ()-N-hydroxy-1-(6-oxo-1(6H)-pyridazinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyformamide; 0423 ()-N-1-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0424 ()-N-1-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0425 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-methyl-2-4-(trifluoromethoxy) 1,1-biphenyl-4-yloxypropyl-N-hydroxyformamide; 0426 ()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(1,6-dihydro-3-methyl-2,6-dioxo-1 (6H)-pyrimidinyl)ethyl-N-hydroxyformamide; 0427 ()-N-hydroxy-N-1-(3-methyl-6-oxo-1(6H)-pyridazinyl)methyl-2-4-4-(trifluoro-methoxy)phenoxyphenylsulfonylethylfornamide; 0428 ()-N-hydroxy-N-1-(1-methyl-1H-indol-4-yl)-2-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0429 ()-N-hydroxy-N-1-(1-methyl-1H-indol-2-yl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0430 ()-N-1-(4-chlorophenyl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0431 ()-N-hydroxy-N-2-4-(trifluoromethoxy)phenoxyphenylsulfonyl-1-4-(trifluoro-methyl)phenylethylformamide; 0432 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoro-methoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0433 ()-N-hydroxy-N-1-(2-thienylthio)methyl-2-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0434 ()-N-hydroxy-N-1-(4-methylphenyl)sulfonylmethylaminomethyl-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide; 0435 ()-N-hydroxy-N-2-(methoxyethoxy)methyl-1-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0436 ()-N-1-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl-2-(4-phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0437 ()-N-hydroxy-N-1-(4-hydroxyphenyl)-2-4-(trifluoromethyl) 1,1-biphenyl-4-ylsulfonylethylformamide; 0438 ()-N-hydroxy-N-1-(2,2-dimethyl-1,3-dioxan-5-yl)-2-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0439 ()-N-hydroxy-N-3-hydroxy-2-(hydroxymethyl)-1-4-(trifluoromethoxy)phenoxy-phenylsulfonylmethylpropylformamide; 0440 ()-N-hydroxy-N-1(hydroxymethyl)-2-(4-chlorophenyl)thiophenylsulfonyl-ethylformamide; 0441 ()-N-hydroxy-N-1-(4-morpholinylmethyl)-2-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0442 ()-N-hydroxy-N-4-hydroxy-1-4-(trifluoromethoxy)phenoxyphenylsulfonyl-butylformamide; 0443 ()-N-1-(1H-isoindole-1,3(2H)-dione)methyl-2-4-(4-chlorophenoxy)phenyl-sulfonylethyl-N-hydroxyformamide; 0444 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-cyano-phenoxy)phenylsulfonylethyl-N-hydroxyformamide; 0445 ()-N-hydroxy-N-1-(2-pyridinyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethylformamide; 0446 ()-N-1-(4-chlorophenoxy)phenylsulfonylmethyl-4-hydroxybutyl-N-hydroxy-formamide; 0447 0448 ()-N-1-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl-3-hydroxypropyl-N-hydroxyformamide; 0449 ()-N-hydroxy-N-1-(4-trifluoromethoxyphenoxy)methyl-2-4-4-(trifluoro-methoxy)phenoxyphenylsulfonylethylformamide; 0450 0451 S-(R*,R*)-N-hydroxy-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-(4-phenyl-1-piperidinyl)phenylsulfonylethylformamide; 0452 ()-N-hydroxy-N-1-(4-trifluoromethoxyphenyl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0453 S-(R*,R*,R*)-N-1-(2,2,5-trimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)-phenoxyphenylsulfonylethyl-N-hydroxyformamide; 0454 ()-N-hydroxy-N-1-(2-trifluoromethylphenyl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethylformamide; 0455 ()-N-hydroxy-N-1-(4-fluorophenyl)-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethylformamide; 0456 ()-N-hydroxy-N-1-(cyclohexyl)-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethylformamide; 0457 ()-(S)-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 0458 ()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-bromophenoxy)phenylsulfonylethyl-N-hydroxyformamide; and 0459 ()-N-hydroxy-N-1-4-4-(trifluorophenoxy)phenylsulfonylmethyl-2-(3,4,5-trimethoxyphenyl)ethylformamide.

Pharmaceutical Compositions 0460 The present invention also provides pharmaceutical compositions which comprise compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. The pharmaceutical compositions may be specially formulated for oral administration in solid or liquid form, for parenteral injection or for rectal administration. 0461 The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally , intracistemally, intravaginally, intraperitoneally or topically (such as powders, ointments or drops), bucally or as an oral or nasal spray. The term parenteral administration, as used herein, refers to modes of administration which include intravenous, intramuscular, inttaperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. 0462 Pharmaceutical compositions of this invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), and suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. 0463 These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents (such as aluminum monostearate and gelatin) which delay absorption. 0464 In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. 0465 Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. 0466 The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable media just prior to use. 0467 Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. 0468 Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. 0469 The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally or in delayed fashion. Examples of embedding compositions which can be used include polymeric substances and waxes. 0470 The active compounds may also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients. 0471 Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof. 0472 Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents. 0473 Suspensions, in addition to the active compounds, may contain suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth and mixtures thereof. 0474 Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. 0475 Compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq. 0476 Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants which may be required. Opthalmic formulations, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient, compositions, and mode of administration. The selected dosage level will depend upon the activity of the particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound at levels lower than required for to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. 0477 Generally dosage levels of about 1 to about 50, more preferably of about 5 to about 20 mg, of active compound per kilogram of body weight per day when administered orally to a mammalian patient. If desired, the effective daily dose may be divided into multiple doses for purposes of administration, e.g. two to four separate doses per day.

Determination of Stromelysin Inhibition 0478 The efficacy of the compounds of this invention as matrix metalloproteinase inhibitors was determined by measuring the inhibition of stromelysin. The inhibition of stromelysin by the compounds of this invention was determined as follows: Recombinant truncated stromelysin (human sequence) produced in E. coli was prepared by expression and purification of the protein as described by Ye et al. (Biochemistry, 1992, 31, 11231-11235, which is incorporated herein by reference). The enzyme was assayed by its cleavage of the thiopeptide ester substrate Ac-Pro-Leu-Gly-2-mercapto-4-methyl-pentanoyl-Leu-Gly-OEt as described by Weingarten and Feder (Anal. Biochem., 1985, 147, 437-440 (1985), which is incorporated herein by reference) as a substrate of vertebrate collagenase. The reported conditions were modified to allow assays to be carried out in a microtiter plate. Upon hydrolysis of the thioester bond, the released thiol group reacted rapidly with 5,5-dithio-bis(2-nitrobenzoic acid) (DTNB) to produce a yellow color which was measured by a microtiter plate reader set at 405 nm. The rates of cleavage of the substrate by stromelysin in the presence or absence of inhibitors were measured in a 30 minute assay at ambient temperature. Solutions of the compounds in DMSO were prepared, and these were diluted at various concentrations into the assay buffer (50 mM MES/NaOH 6.5 with 10 mM CaCl2 and 0.2% Pluronic F-68), which was also used for dilution of the enzyme and substrate. The potency of the compounds IC50 was calculated from the inhibition/inhibitor concentration data. The compounds of this invention inhibited stromelysin as shown by the data for representative examples in Table 1. 1TABLE 1ExampleIC50 (nM)113023632149.1517630712081709100101,500113001218013310144,00015620

Preparation of Compounds of this Invention 0479 The compounds and processes of the present invention will be better understood in connection with the following synthetic schemes which are merely illustrative of the methods by which the compounds of the invention may be prepared and are not intended to limit the scope of the invention as defined in the appended claims. Representative procedures are outlined in the following Schemes 1-5.

Abbreviations 0480 Abbreviations which have been used in the descriptions of the schemes and the examples that follow are: THF for tetrahydrofuran; DMF for N,N-dimethylformamide; rt for room temperature; TBDMSC1 for tert-butyldimethylsilyl chloride; h for hour; decomp. for decomposition; sat. for saturated; LAH for lithiumaluminum chloride; min for minutes; aq. for aqueous; and m-CPBA for meta-chloroperbenzoic acid. 0481 As shown in Scheme 1, deprotonation of the phenolic moiety of 1 with a base, preferably sodium or potassium hydride, and alkylation of the resulting anion with an excess, preferably a two to four-fold excess, of an electrophile, preferably epibromohydrin or epichlorohydrin, provided the alkylated epoxide 2. An excess of a second nucleophile, preferably a two to four-fold excess, was deprotonated with a base such as sodium or potassium hydride and condensed with 2 to provide alcohol 3 which was treated with bis-Boc-hydroxylamine under Mitsunobu conditions to provide the bis-Boc protected hydroxylamine 6. Removal of the Boc-protecting groups with acid, preferably HCI in dioxane or trifluoroacetic acid in methylene chloride, and neutralization of the amine salt with a base, preferably sodium bicarbonate, provided an exposed hydroxylamine moiety which was treated with a formylating agent, preferably formicacetyl anhydride, in solvents such as THF or dichloromethane to provide hydroxamic acid 7. 0482 Alternatively, 2 was converted to the corresponding iodoketone 4 by a two-step procedure which comprised (a) treatment of the epoxide with triphenylphosphine and an iodinating agent, preferably iodine, in an inert solvent such as dichloromethane to provide the corresponding iodoalcohol followed by (b) oxidation to the corresponding iodoketone 4 with a mild oxidizing agent, preferably Dess-Martin periodinane (Dess, D. B.; Martin, J. C., J. Am. Chem. Soc. 1991, 113, 7277-7287, which is incorporated herein by reference). Introduction of R1 was accomplished by alkylation of the desired phenol or benzenenethiol derivative with 4 in the presence of base, preferably potassium carbonate, in a polar solvent such as DMF. The resulting ketone was converted to the corresponding oxime 5 by treatment with hydroxylamine hydrochloride in a hydroxylic solvent, preferably ethanol, with a catalytic amount of base, preferably pyridine. When R1 contained sulfur, the alcohol was oxidized to the corresponding ketone using Dess-Martin periodinane in an inert solvent such as dichloromethane then converted to 5 as described above. Treatment of 5 with a reducing agent, preferably borane pyridine complex, in a hydroxylic solvent, preferably ethanol, and adding excess aqueous hydrochloric acid provided the corresponding hydroxylamine which was formylated as described above to provide 7. Depending on the nature of R1 group, protection and subsequent deprotection of other reactive groups was required to successfully complete the described synthetic sequences. Commonly used protecting groups are disclosed in Greene, Protective Groups In Organic Synthesis, (John Wiley & Sons, New York (1981)), which is incorporated herein by reference. 7

0483 Scheme 2 shows an alternate preparation of intermediate 5. Alkylation of 1 with ethyl bromoacetate was accomplished in the presence of base, preferably potassium carbonate, in a polar solvent, preferably DMF, to provide 8, which was subsequently hydrolyzed to 9 by treatment with aqueous base, preferably lithium hydroxide in a solvent mixture, preferably water and dioxane. Amide 10 was prepared by coupling N,O-dimethylhydroxylamine hydrochloride to 9 with a coupling agent, preferably bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl). Treatment of 10 with R1-MgX, wherein X is Br or Cl, at reduced temperature, preferably 78 C. in an inert solvent, preferably THF, provided ketone 11, which was converted to 5, and finally to 7, as described in Scheme 1. 8

0484 Scheme 3 shows the synthesis of compounds where the introduction of the phenolic and R1 groups was reversed. This route intersects with the route described in Scheme 1 at epoxide 14, and the chemistry described in Scheme 1 may be utilized to convert 14 into the hydroxamic acid by employing HOAr1YAr2 in place of R1H. Heterocyclic derivatives of R1H, preferably those having appropriate pKa's, such as the hydantoin in this scheme, were condensed with the desired olefinic alcohol under Mitsunobu conditions to provide the corresponding N-alkenylheterocycle 12. Treatment of 12 with an alkylating agent, preferably methyl iodide, in the presence of base, preferably sodium hydride, provided N-methyl alkenylheterocycle 13, which was epoxidized with meta-chloroperbenzoic acid (MCPBA) in dichloromethane to provide 14. The reaction sequence described in Scheme 1 was then used to convert 14 to hydroxamic acid 5. 9

0485 wherein the alkylene group is of one to six carbon atoms, n is 1, and R6 and R7 together with the nitrogen aton to which they are attached, form 10

0486 Scheme 4 shows an alternate synthesis of the hydantoin substituted compounds 22 and 23. Alkylation of 16 with a substituted hydantoin 17 in the presence of base, preferably potassium carbonate provides the enol ether 18. Treatment of 18 with a brominating agent such as NBS in acetone, gives the the bromoketone 19 which can then be alkylated with either aryl thiols (20, XS) or substituted phenols (20,, XO) to afford the ketones 21. Ketones 21, wherein Y is a covalent bond could also be prepared from 19 in a two step procedure, first alkylating with either bromo thiophenols (20a, XS) or bromophenols (20a, HO), then coupling the aryl bomides 10a with an appropriate aryl boronic acid following the Suzuki protocol, or an appropriate arul stannane. The reaction sequence described in scheme 1 can then be used to convert 21 into the hydroxamic acids 22. The compounds wherein XS can be converted to the sulfones 23 via oxidation with an appropriate oxidant such as m-chloroperbenzoic acid or oxone. 11

0487 Scheme 5 shows an alternate synthesis of the sulfones 29. Deprotonation of the sulfone 25 with a base such as LDA followed by addition to a ketone or aldehyde 24 gives an alcohol which can be dehydrated either by reaction with acid, such as toluene sulfonic acid or by a stepwide 2 step procedure: first convering the alcohol into a leaving group, such as mesylate via treatment with mesyl chloride and triethyl amine, then eliminating with a base, preferably 1,8-diazabicyclo5.4.0undec-7-ene. Reaction of the olefin with an O-protected hydroxylamime preferably O-benzyl gives the adduct 28. Formylation as previously described in scheme 1 followed by removal of the protecting group, preferably under hydrogenation conditions for the compounds wherin P is benzyl affords the sulfone 29. The sulfone 28 can also be prepared directly via the deprotonation of sulfone 25, with a base such as n-BuLi and subsequent addition, preferably in the presence of boron trifluoride etherate, to a 0-protected oxime 30. 12

0488 The foregoing may be better understood by reference to the following examples which illustrate the methods by which the compounds of the invention may be prepared and are not intended to limit the scope of the invention as defined in the appended claims.

EXAMPLE 1

()-N-1-(4-cyano-1,11-biphenyl-4-yl)oxymethyl-2-phenoxyethyl-N-hydroxyformamide

EXAMPLE 1A

()-3-Phenoxypropan-1,2oxirane 0489 A suspension of sodium hydride (0.47 g, 11.7 mmol) in THF (20 mL) was treated sequentially with a solution of phenol (1.00 g, 10.6 mmol) in THF (20 mL) then epibromohydrin (2.73 mL, 31.8 mmol) in a single portion, refluxed for 2 hours, cooled, treated with 20% aqueous potassium hydrogen sulfate then partitioned between ethyl acetate and brine. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, and concentrated to provide 1.65 g of a golden oil which was purified on silica gel with 10% ethyl acetate/hexanes (500 mL) and 20% ethyl acetate/hexanes to provide 1.19 g (75%) of the title compound. MS (DCI/NH3) m/e 168 (MNH4)and 185 (MNH4NH3).

EXAMPLE 1B

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-phenoxy-2-propanol 0490 A suspension of sodium hydride (0.18 g, 4.39 mmol) in THF (4 mL) was treated sequentially with a solution of 4-hydroxy-4-biphenylcarbonitrile (0.78 g, 3.99 mmol) in THF (4 mL), Example 1A (0.60 g, 3.99 mmol) in THF (2 mL) then DMF (6 mL), refluxed for 1 hour, cooled, treated with 20% aqueous potassium hydrogen sulfate and partitioned between ethyl acetate and brine. The organic layer was washed with saturated aqueous sodium bicarbonate, 15% aqueous sodium hydroxide and brine, dried (Na2SO4), filtered, and concentrated to provide 1.04 g of a yellow oil which was purified on silica gel with 25-30% ethyl acetate/hexanes to provide 0.42 g (22%) of the title compound. 0491 MS (DCI/NH3) m/e 363 (MNH4) and 380 (MNH4NH3).

EXAMPLE 1C

()-N,O-bis(t-butlyoxycarbonyl)-1-(4-(4-carbonitrilephenyl)phenoxy)-3-phenoxy-prop-2-yl-N-hydroxylamine 0492 A solution of Example 1B (0.41 g, 1.19 mmol), triphenylphosphine (0.40 g, 1.54 mmol), and di-Boc-hydroxylamine (0.33 g, 1.42 mmol) in THF (5 mL) was treated dropwise with diethylazodicarboxylate (0.24 mL, 1.54 mmol), stirred at ambient temperature for 1 hour and concentrated. The resulting oil was redissolved in dichloromethane (30 mL) and concentrated under vacuum (2 cycles) to remove any excess THF then purified on silica gel with 15% ethyl acetate/hexanes to provide 0.50 g (75%) of the title compound as a colorless foam. 0493 MS (DCI/NH3) m/e 578 (MNH4).

EXAMPLE 1D

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-phenoxy-prop-2-yl-N-hydroxylamine 0494 A solution of Example 1C (0.45 g; 0.80 mmol) in dichloromethane (3 mL) was treated with trifluoroacetic acid (6 mL), stirred for 15 minutes at ambient temperature, poured into excess saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The resulting organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated to provide 0.70 g of a brown oil which was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.23 g (81%) of deprotected hydroxylamine as a light yellow foam.

EXAMPLE 1E

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-phenoxyethyl-N-hydroxyformamide 0495 A solution of Example 1D (0.15 g, 0.41 mmol) in dichloromethane (2 mL) was cooled to 10 C. and treated with a solution of formicacetyl anhydride (38 mg, 0.43 mmol) in dichloromethane (1 mL), stirred for 15 minutes, diluted with ether and washed sequentially with saturated aqueous sodium bicarbonate, 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, and concentrated to provide 0.17 g of a brown, glassy oil which was purified on silica gel with 97.5% (40% ethyl acetate/hexanes)/2.5% methanol to provide 67 mg (42%) of light brown foam which was recrystallized from ethyl acetate/hexanes/acetone to provide the title compound as light pink, clumpy crystals. 0496 mp 133-135 C.; 0497 1H NMR (300 MHz, CDCl3) 8.15 (br s; 1H), 8.07 (s; 1H), 7.69 (AB; 1H; J9 Hz), 7.62 (AB; 1H; J9 Hz), 7.54 (d; 1H; J9 Hz), 7.32 (dd; 1H; J6.5,8.0 Hz), 6.97-7.06 (m; 3H), 6.92 (d; 2H; J7.5 Hz), 4.24-4.47 (m; 5H); 0498 MS (DCI/NH3) m/e 345 (MNH4HCONHOH); 0499 Anal. calcd for C23H20N2O4: C, 71.12; H, 5.19; N, 7.21. Found: C, 71.04; H, 5.16; N, 7.01.

EXAMPLE 2

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(phenylthio)ethyl-N-hydroxyformamide

EXAMPLE 2A

()-3-(4-(4-Carbonitrilephenyl)phenoxy)propan-1,2oxirane 0500 The title compound was prepared following the procedure from Example 1A but using 4-hydroxy-4-biphenylcarbonitrile (10.0 g, 51.2 mmol) in place of phenol. Purification by trituration with ether provided 9.13 g (71%) the title compound as a chalky solid. 0501 mp 115-116 C.; 0502 MS (DCI/NH3) m/e 269 (MNH4) and 286 (MNH4NH3).

EXAMPLE 2B

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-thiophenoxy-2-propanol 0503 A solution of Example 2A (0.90 g), triethylamine (1.75 mL), and benzenethiol (1.10 mL) in absolute ethanol (14 mL) was heated at reflux for 1 hour, cooled and partitioned between ethyl acetate and 10% aqueous sodium hydroxide. The organic layer was washed sequentially with 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, and concentrated to provide 1.27 g of a thick golden oil which was purified by recrystallization from ethyl acetate/hexanes/methanol to provide the title compound as colorless, clumpy crystals. 0504 mp 105-106 C.; 0505 MS (DCI/NH3) m/e 379 (MNH4).

EXAMPLE 2C

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-thiophenoxy-2-propanone 0506 A suspension of the Dess-Martin periodinane in dichloromethane (25 mL) was treated with Example 2B (2.02 g) in dichloromethane (15 mL), stirred at ambient temperature for 0.5 hours and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with saturated aqueous sodium thiosulfate, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, and concentrated to provide 2.27 g of a clumpy, orange solid which was purified on silica gel with 30% ethyl acetate/hexanes to provide 1.90 g of the title compound as a chalky, light yellow solid. 0507 MS (DCI/NH3) m/e 377 (MNH4).

EXAMPLE 2D

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-thiophenoxy-2-propanone Oxime 0508 A solution of Example 2C (2.02 g) in methanol (20 mL) and THF (10 mL) was treated sequentially with 10 drops of pyridine then hydroxylaminehydrochloride (0.78 g), heated at reflux for 1 hour, cooled and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with water and brine, dried (Na2SO4), filtered, and concentrated to provide 1.90 g of the title compound as a chalky yellow solid which was used without further purification. 0509 MS (DCI/NH3) m/e 375 (MH) and 392 (MNH4).

EXAMPLE 2E

()-N-(4-(4-carbonitrilephenyl)phenoxy)-3-thiophenoxyprop-2-yl)hydroxylamine 0510 A solution of Example 2D (1.90 g) in THF (10 mL) was treated sequentially with absolute ethanol (20 mL), boranepyridine (1.5 mL) then dropwise with 6N aqueous hydrochloric acid, stirred for 1 hour at ambient temperature, poured into excess saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated to provide 2.25 g of an orange oil which was purified on silica gel with 30% ethyl acetate/hexanes to provide 1.26 g of the title compound as a light gold oil. MS (DCI/NH3) m/e 377 (MH) and 394 (MNH4).

EXAMPLE 2F

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(phenylthio)ethyl-N-hydroxyformamide 0511 A solution of compound 2E (1.24 g) in THF (10 mL) was cooled to 23 C. and treated with a solution of formicacetylanhydride (280 L) in THF (2 mL), stirred for 15 minutes, diluted with ether. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate, 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, and concentrated to provide 1.27 g of a glassy orange oil which was purified on silica gel with 97.5% (40% ethyl acetate/hexanes)/2.5% methanol to provide 300 mg of the title compound as a light orange foam. 0512 1H NMR (300 MHz, CDCl3) 7.95 (br s; 1H), 7.90 (s; 1H), 7.70 (AB; 1H; J7.5 Hz), 7.62 (AB; 1H; J7.5 Hz), 7.51 (d; 1H; J9 Hz), 7.20-7.43 (m; 5H), 6.95 (d; 2H; J9 Hz), 4.33 (dd; 1H; J8.5,10.5 Hz), 4.17 (dd; 1H; J4.5,10.5 Hz), 4.0 (m; 1H), 3.36 (dd; 1H; J8.5,14 Hz), 3.28 (dd; 1H; J6,14 Hz); 0513 MS (DCI/NH3) m/e 422 (MNH4). 0514 Anal. calcd for C23H20N2O3S: C, 68.30; H, 4.98; N, 6.73. Found: C, 68.19; H, 4.86; N, 6.73.

EXAMPLE 3

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)ethyl-N-hydroxyformamide

EXAMPLE 3A

()-3-(4-(4-Carbonitrilephenyl)phenoxy)-3-iodo-2-propanol 0515 A solution of iodine (1.54 g, 6.0 mmol) in dichloromethane (20 mL) was treated with triphenylphosphine (1.58 g, 6.0 mmol), stirred for 5 minutes, treated with 3-(4-carbonitrilephenyl)phenoxy)propan-(1,2) oxirane (1.0 g, 4.0 mmol) in a single portion, stirred at ambient temperature for 30 minutes, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide 3 g of crude product which was purified on silica gel with 30% ethyl acetate/hexanes to provide 1.38 g (91%) of the title compound. 0516 MS (DCI/NH3) m/e 397 (MNH4) and 414 (MNH4NH3).

EXAMPLE 3B

3-(4-(4-Carbonitrilephenyl)phenoxy)-1-iodopropan-2-one 0517 The title compound was prepared as in Example 2C but using Example 3A (1.0 g, 2.63 mmol) in place of 3-(4-(4-carbonitrilephenyl)phenoxy)-1-thiophenoxypropan-2-ol. Purification on silica gel with 20% ethyl acetate/hexanes provided 0.65 g (66%) of the title compound. 0518 MS (DCI/NH3) m/e 395 (MNH4) and 412 (MNH4NH3).

EXAMPLE 3C

1-(4-(4-Carbonitrilephenyl)phenoxy)-3-phthaloylpropan-2-one 0519 A solution of Example 3B (1.38 g; 3.66 mmol) in DMF (20 mL) was treated with potassium phthalimide (1.02 g; 5.50 mmol), stirred at ambient temperature for 10 minutes, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide 1.1 g of crude product which was purified on silica gel with ethyl acetate to provide 0.98 g (67%) of the title compound. 0520 MS (DCI/NH3) m/e 414 (MNH4).

EXAMPLE 3D

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(2,3-dihydro-1,3-dioxo-1H-isoindol-2-yl)ethyl-N-hydroxyformamide 0521 The title compound was prepared according to Example 2D but using Example 3C (0.56 g, 1.41 mmol) in place of 1-(4-(4-carbonitrilephenyl)phenoxy)-3-thiophenoxypropan-2-one to provide the corresponding oxime which was reduced according to Example 2E using 1-(4-(4-carbonitrilephenyl)phenoxy)-3-phthaloylpropan-2-one oxime in place of 1-(4-(4-carbonitrilephenyl)phenoxy)-3-thiophenoxypropan-2-one oxime. The resulting hydroxylamine was formylated according to Example 2F but using 1-(4-(4-carbonitrilephenyl)phenoxy)-3-phthaloyl-2-propylhydroxylamine in place of 1-(4-(4-carbonitrilephenyl)phenoxy)-3-thiophenoxy-2-propylhydroxylamine. Purification on silica gel with 60% ethyl acetate/hexanes provided 0.185 g (30%) of the title compound. 0522 mp 199-202 C.; 0523 1H NMR (300 MHz, CDCl3) 10.06 (s; 0.5H), 9.67 (s; 0.5H), 8.32 (s; 0.5H), 7.99 (s; 0.5H), 7.88 (m; 8H), 7.72 (m; 2H), 7.02 (m; 3H), 4.96 (m; 0.5H), 4.52 (m; 0.5H), 4.25 (m; 2H), 3.78-4.00 (m; 2H); 0524 MS (DCI/NH3) m/e 459 (MNH4); 0525 Anal. calcd for C25H19N3O5: C, 67.96; H, 4.304; N, 9.51. Found: C, 67.43; H, 4.34; N, 9.04.

EXAMPLE 4

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxoimidazolidiny-1-yl)ethyl-N-hydroxyformamide

EXAMPLE 4A 0526 ()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-((5,5-dimethyl)hydantoin-3-yl)-2-propanol 0527 A solution of 5,5-dimethylhydantoin (0.26 g, 1.99 mmol) in THF (20 mL) was treated with potassium tert-butoxide (1.99 mL, 1.99 mmol), stirred for 5 minutes, treated with 3-(4-carbonitrilephenyl)phenoxy)-(1,2) oxirane (0.50 g, 1.99 mmol) in a single portion, stirred at 70 C. for 6 hours, treated with excess saturated aqueous ammonium chloride and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with ethyl acetate to provide 0.70 g (93%) of the title compound. 0528 MS (DCI/NH3) m/e 397 (MNH4).

EXAMPLE 4B

()-1-(4-(4-Carbonitrilephenyl)phenoxy)-3-(3-(5,5-dimethyl)hydantoin)-2-(t-butyldimethylsilyloxy)propane 0529 A solution of Example 4A (0.40 g, 1.06 mmol) in dichloromethane (20 mL) was treated with tert-butyldimethylsilyl chloride (0.24 g, 1.60 mmol) and imidazole (0.1 g, 1.6 mmol), stirred at ambient temperature for 30 minutes, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a solid which was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.50 g (95%) of the title compound. 0530 MS (DCI/NH3) m/e 511 (MNH4).

EXAMPLE 4C

()-1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidin-1-yl)-2-t-butlydimethylsilyloxypropane 0531 A solution of 4B (0.60 g, 1.20 mmol) in THF (20 mL) was treated with sodium hydride (0.035 g, 1.40 mmol) then iodomethane (0.26 g, 1.8 mmol) in a single portion, stirred at 70 C. for 30 minutes, treated with saturated aqueous ammonium chloride and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide the title compound as white crystals.

EXAMPLE 4D

()-1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidin-1-yl)-2-propanol 0532 A solution of Example 4C in THF (30 mL) was treated with tetrabutylammonium fluoride (1M in THF, 2.0 mL, 2.0 mmol), stirred at ambient temperature for 30 minutes, treated with water and partioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide crude product which was purified on silica gel with ethyl acetate to provide 0.47 g (100%) of the title compound. 0533 MS (DCI/NH3) m/e 411 (MNH4).

EXAMPLE 4E

1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0534 Example 4D (0.59 g, 1.50 mmol) was processed according to the procedure in Example 2C. Purification of the crude product on silica gel with 50% ethyl acetate/hexanes provided 0.58 g (98%) of the title compound. 0535 MS (DCI/NH3) m/e 409 (MNH4).

EXAMPLE 4F

()-1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-prop-2-yllhydroxylamine 0536 Example 4E (0.57 g, 1.46 mmol) was processed according to the procedures in Examples 2D and 2E. Purification of the crude product on silica gel with 60% ethyl acetate/hexanes provide 0.31 g (52%) of the title compound. 0537 MS (DCI/NH3) m/e 409 (MH).

EXAMPLE 4G

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)ethyl-N-hydroxyformamide 0538 Example 4F was processed according to the procedure in Example 2F. Purification of the crude product on silica gel with 60% ethyl acetate/hexanes provided 0.19 g (60%) of the title compound. 0539 mp 65-67 C.; 0540 MS (DCI/NH3) m/e 437 (MH) and 454 (MNH4). 0541 1H NMR (300 MHz, CDCl3) 9.90 (s; 0.5H), 9.58 (s; 0.5H), 8.32 (s; 0.5H), 7.92 (s; 0.5H), 7.85 (m; 4H), 7.72 (d; 2H; J5.6 Hz), 7.02 (dd; 2H; J5.5, 2.5 Hz), 4.86 (m; 0.5H), 4.42 (m; 0.5H), 4.08-4.02 (m; 2H), 3.82-3.70 (m; 1H), 3.55-4.05 (m; 1H), 2.8 (s; 1.5H), 2.78 (s; 1.5H), 1.5 (s; 3H), 1.48 (s; 3H); 0542 Anal. calcd for C23H24N4O5: C, 63.23; H, 5.50; N, 12.83. Found: C, 62.96; H, 5.55; N, 12.45.

EXAMPLE 5

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-3-(3,4,4-trimethyl-2,5-dioxoimidazolidiny-1-yl)propyl-N-hydroxyformamide

EXAMPLE 5A

1-(Prop-2-enyl)-4,4-dimethyl-2,5-dioxoimidazolidine 0543 A solution of 3-buten-1-ol (1 g, 13.9 mmol), triphenylphosphine (4.73 g, 18 mmol) and 5,5-dimethylhydantoin (2.1 g, 16.7 mmol) in THF (50 mL) was treated dropwise with diethylazodicarboxylate (3.13 g, 18.0 mmol), stirred at ambient temperature for 1 hour, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide crude product which was purified on silica gel with 50% ethyl acetate/hexanes to provide 2.5 g (100%) of the title compound.

EXAMPLE 5B

1-(Prop-2-enyl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0544 A solution of Example 5A (2.3 g, 12.6 mmol) in THF (50 mL) was treated with sodium hydride (0.45 g, 18.9 mmol) then iodomethane (2.7 g, 18.9 mmol) in a single portion, refluxed for 2 hours, cooled, treated with water, and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide 3.5 g of a yellow solid which was purified on silica gel with 50% ethyl acetate/hexanes to provide 2.4 g (98%) of the title compound. 0545 MS (DCI/NH3) m/e 214 (MNH4).

EXAMPLE 5C

()-1-((1,2Oxiranyl)propyl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0546 A solution of Example 5B (3.0 g, 15.3 mmol) in dichloromethane (50 mL) was treated with m-chloroperbenzoic acid (4.4 g), stirred at ambient temperature for 2 hours, treated with saturated aqueous sodium carbonate and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to a solid which was purified on silica gel with 70% ethyl acetate/hexanes to provide 1.5 g (46%) of the title compound. 0547 MS (DCI/NH3) m/e 213 (M1) and 230 (MNH4).

EXAMPLE 5D

()-1-(2-Hydroxy-3-iodo-propyl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0548 A solution of iodine (0.29 g, 1.88 mmol) in dichloromethane (20 mL) was treated with triphenylphosphine (0.3 g, 1.88 mmol), stirred for 5 minutes, treated with Example 5C (0.2 g, 0.94 mmol) in a single portion, stirred at ambient temperature for 30 minutes, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 75% ethyl acetate/hexanes to provide 0.26 g (80%) of the title compound. 0549 MS (DCI/NH3) m/e 342 (MH) and 358 (MNH4).

EXAMPLE 5E

1-(3-Iodo-propan-2-onyl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0550 Example 5D was processed according to the procedure in Example 2C. Purification the crude product on silica gel with 60% ethyl acetate/hexanes provided 0.3 g (96%) of the title compound. 0551 MS (DCI/NH3) m/e 339 (MH) and 356 (MNH4).

EXAMPLE 5F

()-1-(3-(4-Cyano-1,1-biphenyl-4-yl)oxy-propan-2-on-1-yl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0552 A solution of 4-hydroxy-4-biphenylcarbonitrile (0.38 g, 1.9 mmol) in THF (50 mL) was treated with potassium carbonate (0.5 g) then Example 5E (0.44 g, 1.30 mmol), refluxed for 7 hours, cooled, treated with 10% aqueous HCl and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 75% ethyl acetate/hexanes to provide 0.52 g (99%) of the title compound. 0553 MS (DCI/NH3) m/e 423 (MNH4).

EXAMPLE 5G

()-1-(3-(4-Cyano-1,1-biphenyl-4-yl)oxy-propan-2-oximino-1-yl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0554 Example 5F was processed according to the procedure in Example 2D. The crude product was purified on silica gel with 75% ethyl acetate/hexanes to provide 0.68 g (1.60 mmol; 100%) of the title compound. 0555 MS (DCI/NH3) m/e 439 (MNH4).

EXAMPLE 5H

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 0556 Example 5G was processed according to the procedures in Examples 2E and 2F. Purification of the crude product on silica gel with 75% ethyl acetate/hexanes provided 0.408 g (56%) of the title compound. 0557 mp 68-70 C.; 0558 1H NMR (300 MHz, CDCl3) 9.99 (s; 0.5H), 9.46 (s; 0.5H), 8.35 (s; 0.5H), 7.92 (s; 0.5H), 7.92 (d; 2H; J5.6 Hz), 7.85 (d; 2H; J5.6 Hz), 7.70 (d; 2H; J5.6 Hz), 7.05 (d; 2H; J5.6 Hz), 4.52 (m; 0.5H), 4.18-3.95 (m; 3.5H), 3.46 (m; 2H), 2.82 (s; 1.5H), 2.79 (s; 1.5H), 2.02-1.72 (m; 1H), 1.32 (s; 6H); 0559 MS (DCI/NH3) m/e 468 (MNH4); 0560 Anal. calcd for C24H26N4O5: C, 63.93; H, 5.77; N, 12.43. Found: C, 63.38; H, 5.99; N, 11.97.

EXAMPLE 6

()-N-1-3-(cyanomethyl)-1,1-biphenyl-4-yloxymethylpentyl-N-hydroxyformamide

EXAMPLE 6A

4-((t-Butyldimethyl)silyloxy)phenyl Boronic Acid 0561 A solution of (4-bromophenoxy)trimethylsilane (69 g, 20.9 mmol) in THF (60 mL) was treated with n-butyllithium at 78 C., stirred for 15 minutes, treated with triisopropyl borate, stirred at 78 C. for 10 minutes, warmed to ambient temperature, stirred for another 30 minutes, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (MgSO4), filtered, and concentrated to provide 4.79 g (91%) of the title compound.

EXAMPLE 6B

4-Hydroxy-3-biphenylcarbonitrilemethane 0562 A mixture of Example 6A (4.8 g, 19.0 mmol), 3-bromophenyl acetonitrile (3.1 g, 16.0 mmol), cesium carbonate (7.8 g, 24.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.55 g, 0.48 mmol) was treated via syringe with DMF (30 mL) under positive nitrogen pressure, stirred at 100 C. for 10 h, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (MgSO4), filtered, and concentrated to provide a brown oil which was purified on silica gel with 50% ethyl acetate/hexanes to provide 3.3 g (82%) of the title compound. 0563 MS (DCI/NH3) m/e 227 (MNH4).

EXAMPLE 6C

Ethyl 2-(4-(3-carbonitrilemethylphenyl)phenoxy)acetate 0564 A solution of 6B (0.5 g, 2.4 mmol) in THF (20 mL) was treated with potassium carbonate (0.5 g) and ethyl bromoacetate (0.6 g, 3.6 mmol), refluxed for 3 hours, cooled, treated with 10% aqueous HCl and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.48 g (68%) of the title compound. 0565 1H NMR (300 MHz, CDCl3) 7.52 (m; 4H), 7.40 (m; 1H), 7.36 (m; 1H), 7.0 (m; 2H), 4.65 (s; 2H), 4.30 (q; 2H; J4.8 Hz), 3.80 (s; 2H), 1.32 (t; 3H; J4.8 Hz).

EXAMPLE 6D

2-(4-(3-Carbonitrilemethylphenyl)phenoxy)acetic Acid 0566 A solution of 6C (0.47 g, 1.6 mmol) in 1,4-dioxane (20 mL) and water (10 mL) was treated with lithium hydroxide (0.5 g), stirred at ambient temperature for 30 minutes, treated with 10% aqueous HCl and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.37 g (83%) of the title compound. 0567 1H NMR (300 MHz, CDCl3) 7.60 (m; 4H), 7.46 (m; 1H), 7.32 (m; 1H), 7.02 (m; 2H), 4.72 (s; 2H), 4.08 (s; 2H).

EXAMPLE 6E

N,O-dimethyl-2-(4-(3-carbonitrilemethylphenyl)phenoxy)acetyl hydroxylamine 0568 A solution of 6D (0.35 g, 1.3 mmol), triethylamine (0.5 mL) and bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (0.78 g, 2.6 mmol) in dichloromethane (20 mL) was treated with N,O-dimethyl-hydroxylamine hydrochloride (0.25 g, 2.6 mmol), stirred at ambient temperature for 2 hours, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.28 g (69%) of the title compound. 0569 1H NMR (300 MHz, CDCl3) 7.59 (m; 4H), 7.46 (m; 1H), 7.32 (m; 1H), 7.02 (m; 2H), 4.96 (s; 2H), 4.08 (s; 2H), 3.78 (s; 3H), 3.15 (s; 3H).

EXAMPLE 6F

1-(4-(3 -Carbonitrilemethylphenyl)phenoxy)-2-hexanone 0570 A solution of 6E (0.27 g, 0.85 mmol) in THF (10 mL) was treated with n-butylmagnsium bromide (1 mL, 2.0 mmol) at 78 C., stirred at 78 C. for 1 h, treated with water and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and concentrated to provide a yellow solid which was purified on silica gel with 25% ethyl acetate/hexanes to provide 0.15 g (59%) of the title compound. 0571 1H NMR (300 MHz, CDCl3) 7.52 (m; 4H), 7.42 (m; 1H), 7.28 (m; 1H), 6.98 (m; 2H), 4.60 (s; 2H), 3.82 (s; 2H), 2.62 (t; 2H; J5.5 Hz), 1.64 (m; 2H); 1.38 (m, 2H), 0.92 (t; 3H; J4.8 Hz).

EXAMPLE 6G

()-N-1-3-(cyanomethyl)-1,1-biphenyl-4-yloxymethylpentyl-N-hydroxyformamide 0572 Example 6F (0.15 g, 0.50 mmol) was processed according to the procedures described in Examples 2D-F (inclusive). Purification of the crude final product on silica gel with 40% ethyl acetate/hexanes provided 0.07 g (41%) of the title compound. 0573 mp 99-101 C.; 0574 MS (DCI/NH3) m/e 352 (MNH4). 0575 1H NMR (300 MHz, CDCl3) 8.58 (brs; 0.5H), 8.04 (brs; 0.5H), 8.0 (s; 1H), 7.48 (m; 4H), 7.42 (m; 1H), 7.26 (m; 1H), 6.98 (m; 2H), 4.05 (t; 1H; J5.6 Hz), 3.8-4.0 (m; 2H), 3.80(s; 2H), 1.92 (m; 1H0, 1.60 (m; 2H), 1.38 (m; 3H), 0.98 (t; 3H; J4.8 Hz). 0576 Anal. calcd for C21H24N2O3: C, 71.50; H, 6.81; N, 7.94. Found: C, 71.44; H, 6.90; N, 7.80.

EXAMPLE 7

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-3-methylbutyl-N-hydroxyformamide 0577 4-hydroxy-4-biphenylcarbonitrile (1.0 g, 5.12 mmol) was processed according to the procedures described in Examples 6C-G (inclusive), but substituting isobutylmagnesium bromide for the n-butylmagnesium bromide used in Example 6F. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.036 g of the title compound. 0578 mp 112-113 C.; 0579 MS (DCI/NH3) m/e 356 (MNH4). 0580 1H NMR (300 MHz, CDCl3) 7.95 (s; 1H), 7.70 (d; 2H; J5.6 Hz), 7.62 (d; 2H; J5.8), 7.52 (d; 2H; J5.8 Hz), 6.98 (d; 2H; J5.8 Hz), 4.25 (m; 1H), 3.92-4.05 (m; 2H), 1.95 (m; 1H), 1.75 (m; 1H), 1.35(m; 1H), 1.00 (d; 3H; J4.8 Hz), 0.98 (d; 3H; J4.8 Hz). 0581 Anal. calcd for C20H22N2O3: C, 70.92; H, 6.50; N, 8.27. Found: C, 70.91; H, 6.68; N, 8.13.

EXAMPLE 8

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-methylbutyl-N-hydroxyformamide 0582 The title compound was prepared following the sequence of steps described in Example 7 but substituting sec-butylmagnesium chloride for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.10 g of the title compound. 0583 mp 96-98 C.; 0584 MS (DCI/NH3) m/e 356 (MNH4). 0585 1H NMR (300 MHz, CDCl3) 7.95 (s; 1H), 7.70 (d; 2H; J5.6 Hz), 7.62 (d; 2H; J5.8), 7.52 (d; 2H; J5.8 Hz), 6.98 (d; 2H; J5.8 Hz), 4.32 (m; 1H), 4.15 (m; 2H), 3.65 (m; 1H), 1.98 (m; 1H), 1.62 (m; 1H), 1.02 (m; 3H), 0.98 (m; 3H;). 0586 Anal. calcd for 0.8 H2OC20H22N2O3: C, 68.03; H, 6.69; N, 7.90. Found: C, 68.60 ; H, 6.58; N, 7.23.

EXAMPLE 9

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethylpentyl-N-hydroxyformamide 0587 The title compound was prepared following the sequence of steps described in Example 7 but substituting n-butylmagnesium bromide for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.210 g of the title compound. 0588 mp 105-108 C.; 0589 MS (DCI/NH3) m/e 356 (MNH4). 0590 1H NMR (300 MHz, CDCl3) 7.95 (s; 1H), 7.70 (d; 2H; J5.6 Hz), 7.62 (d; 2H; J5.8), 7.52 (d; 2H; J5.8 Hz), 6.98 (d; 2H; J5.8 Hz), 4.25 (m; 1H), 3.99-3.82 (m; 2H), 1.92 (m; 1H), 1.60 (m; 2H), 1.40 (m; 3H), 0.98 (t; 3H; J4.3 Hz). 0591 Anal. calcd for 0.5C6H6C20H22N2O3: C, 73.13; H, 6.62; N, 7.42. Found: C, 73.18; H, 6.65; N, 7.39.

EXAMPLE 10

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(4-methylphenyl)ethyl-N-hydroxyformamide 0592 The title compound was prepared following the sequence of steps described in Example 7 but substituting 4-methylbenzylmagnesium bromide for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.24 g of the title compound. 0593 mp 173-175 C.; 0594 MS (DCI/NH3) m/e 404 (MNH4). 0595 1H NMR (300 MHz, CDCl3) 7.70 (d; 2H; J5.6 Hz), 7.68 (s; 1H), 7.62 (d; 2H; J5.8), 7.52 (d; 2H; J5.8 Hz), 7.12 (s; 4H), 6.98 (d; 2H; J5.8 Hz), 4.35 (m; 1H), 4.12-3.98 (m; 2H), 3.15 (m; 1H), 2.94 (m; 1H), 1.35 (s; 3H). 0596 Anal. calcd for C24H22N2O3: C, 74.52; H, 5.69; N, 7.24. Found: C, 73.95; H, 5.79; N, 7.06.

EXAMPLE 11

()-N-2-(4-cyano-1,1-biphenyl-4-yl)oxy-1-(4-fluorophenyl)ethyl-N-hydroxyformamide 0597 The title compound was prepared following the sequence of steps described in Example 7, but substituting 4-fluorophenylmagnesium bromide for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.285 g of the title compound. 0598 mp 194-196 C.; 0599 MS (DCI/NH3) m/e 394 (MNH4); 0600 1H NMR (300 MHz, CDCl3) 9.70 (brs; 1H), 8.42 (s; 0.5H), 8.28 (s; 0.5H), 7.86 (m; 4H), 7.72 (d; 2H; J5.6 Hz), 7.55 (m; 2H), 7.25 (m; 2H), 7.12 (d; 2H; J5.8 Hz), 5.72 (brs; 0.5H), 5.35 (brs; 0.5H), 4.60 (m; 1H), 4.36 (m; 1H); 0601 Anal. calcd for C22H17N2O3F: C, 70.14; H, 4.45; N, 7.44. Found: C, 70.19; H, 4.25; N, 7.30.

EXAMPLE 12

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(4-fluorophenyl)ethyl-N-hydroxyformamide 0602 The title compound was prepared following the sequence of steps described in Example 7 but substituting 4-fluorobenzylmagnesium bromide for isobutylmagnesium bromide. Purification of the crude final product on silica gel with 30% ethyl acetate/hexanes provided 0.22 g of the title compound. 0603 MS (DCI/NH3) m/e 408 (MNH4); 0604 1H NMR (300 MHz, CDCl3) 8.35 (brs; 1H), 7.65 (m; 5H), 7.52 (d; 2H; J5.6 Hz), 7.20 (m; 2H), 6.98 (m; 4H), 4.35 (m; 1H), 4.15-3.98 (m; 2H), 3.18 (dd; 1H; J6.0, 9.0 Hz), 2.95 (dd; 1H; J3.0, 9.0 Hz); 0605 Anal. calcd for C23H19N2O3F: C, 70.69; H, 4.87; N, 7.17. Found: C, 70.38; H, 4.96; N, 6.98.

EXAMPLE 13

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethylethyl-N-hydroxyformamide

EXAMPLE 13A

(4-(4-Carbonitrilephenyl)phenoxy)propan-2-one 0606 A solution of 4-(4-carbonitrilephenyl)phenol (4.86 g, 24.9 mmol) in DMF (100 mL) was treated with potassium carbonate (13.8 g, 99.6 mmol), heated at 50 C. for 10 minutes, treated in a single portion with chloroacetone (2.48 mL, 30 mmol), stirred for 4 hours at ambient temperature and partitioned between 3:1 ether:hexanes and saturated aqueous sodium carbonate. The organic layer was dried (MgSO4), filtered, and concentrated under vacuum to of its original volume to cause precipitation of product from solution. The solution was treated with more ether and stored at 20 C. for 17 hours. The title compound (2.01 g, 32%) was collected by filtration and dried under vacuum. 0607 MS (DCI/NH3) m/e 251 (M), 269 (MNH4) and 286 (MNH4NH3).

EXAMPLE 13B

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethylethyl-N-hydroxyformamide 0608 The title compound was obtained following the procedures in Examples 2D-F (inclusive) but substituting Example 13A (2.00 g, 7.96 mmol) for Example 2C. Purification of the crude final product on silica gel with 5% methanol/dichloromethane provided 325 mg of the title compound. 0609 mp 141-144 C.; 0610 1H NMR (300 MHz, d6-DMSO) 9.88 and 9.45 (br s; 1H), 8.02 and 8.33 (s; 1H), 7.90 (AB; 2H; J7.5 Hz), 7.84 (AB; 2H; J7.5 Hz), 7.61 (d; 2H; J9 Hz), 7.06 (d; 2H; J9 Hz), 4.67 (m; 0.32H), 3.92-4.25 (m; 2.68H), 1.23 and 1.18 (d; 3H; J6 Hz); 0611 MS (DCI/NH3) m/e 314 (MNH4); 0612 Anal. calcd for C17H16N2O3: C, 68.90; H, 5.44; N, 9.45. Found: C, 68.61; H, 5.55; N, 9.21.

EXAMPLE 14

N-2-(4-cyano-1,1-biphenyl-4-yl)oxyethyl-N-hydroxyacetamide

EXAMPLE 14A

2-(4-(4-Carbonitrilephenyl)phenoxy)-bromoethane 0613 A solution of 4-(4-carbonitrilephenyl)phenol (3.00 g, 24.8 mmol) in DMF (20 mL) was treated with potassium carbonate (8.24 g, 99.4 mmol) and 1,2-dibromoethane (6.42 mL, 124 mmol), heated at 50 C. for 19 hours and partitioned between 3:1 ether:hexanes and water. The organic layer was separated and the aqueous layer was extracted with 3:1 ether:hexanes. The combined organic layers were dried (MgSO4), filtered, and concentrated. Purification of the crude product on silica gel with 50% dichloromethane/hexanes) provided a white solid which was recrystallized from ether/pentane to provide 1.25 g (17%) of the title compound as colorless needles. MS (DCI/NH3) m/e 301/303 (M), 319/321 (MNH4) and 336/338 (MNH4NH3).

EXAMPLE 14B

N,O-bis(t-butyloxycarbonyl)-2-(4-(4-carbonitrilephenyl)phenoxy)ethyl-N-hydroxylamine 0614 A solution of N,O-bis(t-butyloxycarbonyl)-N-hydroxylamine (443 mg, 1.9 mmol) in DMF (15 mL) was treated with a 60% oil dispersion of sodium hydride (76 mg, 1.9 mmol), stirred at ambient temperature for 15 minutes, treated with Example 13A (0.54 g, 1.79 mmol), stirred for 4 hours at ambient temperature and partitioned between 1:1 ether:hexanes and saturated aqueous ammonium chloride. The organic layer was separated, and the aqueous layer was extracted with 1: 1 ether:hexanes. The combined organic layers were dried (MgSO4), filtered, and concentrated. Purification on silica gel with 10% ethyl acetate/hexanes provided 0.65 g (80%) of the title compound as colorless viscous oil. 0615 MS (DCI/NH3) m/e 472 (MNH4).

EXAMPLE 14C

2-(4-(4-Carbonitrilephenyl)phenoxy)ethyl-N-hydroxylamine hydrochloride 0616 Example 14B (0.64 g, 1.41 mmol) was treated with 4N hydrochloric acid in dioxane (10 mL) and stirred at ambient temperature for 2.5 hours, during which time a colorless precipitate formed. The precipitate was collected by filtration, washed with dioxane, and dried to afford the HCl salt of the title compound as a colorless solid (0.22 g, 56%).

EXAMPLE 14D

N,O-bis(acetyl)-2-(4-(4-carbonitrilephenyl)phenoxy)ethyl-N-hydroxylamine 0617 A solution of Example 14C (27 mg, 0.093 mmol) in THF at 0 C. was treated with triethylamine (32 L, 0.23 mmol), stirred for 1 hour at 0 C., treated dropwise with acetyl chloride (16 L), stirred for 1 hour at 0 C. and 18 hours at ambient temperature and partitioned between 1N aqueous hydrochloric acid and ether. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4), filtered, and concentrated. Purification of the residue on silica gel with 2% acetone/dichloromethane provided 29 mg (83%) of the title compound. MS (DCI/NH3) m/e (MNH4).

EXAMPLE 14D

N-2-(4-cyano-1,1-biphenyl-4-yl)oxyethyl-N-hydroxyacetamide 0618 A solution of Example 14D (29 mg, 0.077 mmol) in THF (5 mL) and ethanol (2 mL) was cooled to 0 C., treated with aqueous lithium hydroxide (0.31 mL of 1.0 N lithium hydroxide), stirred at 0 C. for 10 minutes and at ambient temperature for 1.5 hours and partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ether. The combined organic layers were washed with 1N aqueous hydrochloric acid, dried (MgSO4), filtered, and concentrated to a semi-solid which was purified by trituration with ethyl acetate to provide 19.7 mg (86%) of the title compound as a colorless solid. 0619 mp 174-175 C.; 0620 1H NMR (300 MHz, d6-DMSO) 9.90 (br s; 1H), 7.88 (AB; 2H; J7.5 Hz), 7.84 (AB; 2H; J7.5 Hz), 7.71 (d; 2H; J8.5 Hz), 7.07 (d; 2H; J8.5 Hz), 4.20 (t; 2H; J7.5,7.5 Hz), 3.89 (t; 2H; J7.5,7.5 Hz), 2.02 (s; 3H); 0621 MS (DCI/NH3) m/e 297 (MH) and 314 (MNH4); 0622 Anal. calcd for C17H16N2O3(0.25H2O): C, 67.87; H, 5.52; N, 9.31. Found: C, 67.65; H, 5.55; N, 9.12.

EXAMPLE 15

N-2-(4-cyano-1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 0623 A solution of Example 14C (78 mg, 0.27 mmol) in THF (2.0 mL) was treated with triethylamine (75 L, 0.54 mmol) and then dropwise with formicacetyl anhydride (41 mg, 0.30 mmol) in THF (0.5 mL), stirred for 2 hours at ambient temperature and partitioned between ethyl acetate and 1N aqueous hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried (MgSO4), filtered, and concentrated. Purification by chromatography on silica gel with 0.2% acetic acid/ethyl acetate and subsequent recrystallization from cold methanol provided 14.7 mg (19%) of the title compound. 0624 mp 142-145 C.; 0625 1H NMR (300 MHz, d6-DMSO) 10.17 and 9.74 (br s; 1H), 8.34 and 7.98 (br s; 1H), 7.88 (AB; 2H; J7.5 Hz), 7.84 (AB; 2H; J7.5 Hz), 7.73 (d; 2H; J8.5 Hz), 7.07 (d; 2H; J8.5 Hz), 4.14-4.26 (m; 2H), 3.77-3.88 (m; 2H); 0626 MS (DCI/NH3) m/e 300 (MNH4); 0627 Anal. calcd for C16H14N2O3(0.125H2O): C, 67.54; H, 5.05; N, 9.84. Found: C, 67.59; H, 5.32; N, 9.53.

EXAMPLE 16

N-1-4-(2E-phenylethenyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 16A

3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-2-methoxymethyloxy-prop-1-ene 0628 A mixture of 1,5,5 trimethylhydantoin (7.0 g, 49.2 mmol), powdered potassium carbonate (8.16 g, 59 mmol) and 2-methoxymethyloxy-allyl chloride (7.65 g, 56 mmol) in dry DMF (100 mL) was heated to 100 C. with stirring for 1.5 h. The reaction mixture was cooled, fliltered and the filtrate was concentrated, then partitioned between ethyl acetate and water. The organic extract was washed twice with water, brine, dried and concentrated, then purified via silica gel chromatography eluting with 50% ethyl acetate: hexane to give 10.58 g (89%) of the title compound. 0629 MS (DCI/NH3) m/e 243 (MH) and 260 (MNH4).

EXAMPLE 16B

1-bromo-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)propan-2-one 0630 A 0 C. solution of example 16A (10.58 g, 43.7 mmol) in acetone (200 mL) was treated sequentially with a solution of potassium carbonate (0.58 g, 4.2 mmol) in water (60 mL) and N-bromo succinimide (8.56 g, 48 mmol)and the resulting mixture was stirred with the ice bath in place. An additional 2 portions of 1.5 g of N-bromo succinimide were added after 1 and 2 h respectively. The ice bath was then removed and the reaction was allowed to stir for an additional 10 min, then was concentrated and extracted twice with ethyl acetate. The combined extracts were washed with aq. 0.5 M NaHSO3, 1M NaHCO3, water, brine, dried, filtered, and concentrated. The residue was purified via silica gel chromatography eluting with 50% ethyl acetate: hexane to give 7.39 g (61%) of the title compound. 0631 MS (DCI/NH3) m/e 277/279 (MH)and 294/296 (MNH4).

EXAMPLE 16C

1-(4-bromophenyloxy)-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0632 To a suspension of 4-bromophenol (3.99 g, 23.0 mmol) and cesium carbonate (7.45 g, 22.9 mmol) in DMF (150 mL) was added a solution of bromoketone 16B (3 g, 11.5 mmol) in DMF (5 mL), drop-wise over 30 minutes. The suspension held at rt for 16 h, diluted with ethyl acetate (500 mL) and the organics washed with water, brine and dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (hexane/ethyl acetate 1:1) gave 2.55 g of 16C as a white solid.

EXAMPLE 16D 0633 To a warm (100) solution of 16C (0.5 g, 1.35 mmol) and tributyl(phenylethynyl)tin (0.64 g, 1.62 mmol, Aldrich) in toluene (25 mL) was added a catalytic amount of Pd(PPh3)4. The reaction was brought to reflux and held for 7 h. The resulting black solution was diluted with ethyl acetate (125 mL) and the organics washed with 1 M NaOH, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (gradient elution; hexane/ethyl acetate 4:1 to 1:1) gave 0.24 g of the desired compound after trituration with diethyl ether.

EXAMPLE 16E

N-1-4-(2E-phenylethenyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0634 The title compound was prepared in the same manner as example 2D,E,F substituting 16D for 2C. 0635 1H NMR (300 MHz, d6-DMSO) 9.90 (s, 0.5H), 9.58 (s, 0.5H), 8.31 (s, 0.5H), 7.9 (s, 0.5H), 7.57-7.54 (m, 6H), 7.38-7.33 (m, 2H), 7.26-7.08 (m, 6H), 6.94-6.90 (m, 2H), 4.80-4.60 (m, 0.5H), 4.55-4.40 (m, 0.5H), 4.16-4.04 (m, 4H), 3.76-3.73 (m, 2H), 3.61-3.57 (2, 2H), 2.79 (s, 6H), 1.28 (s, 12H); 0636 MS (ESI) m/e MH (436), MH (438); 0637 Anal. Calcd for: C24H27N3O5.H2O: C, 63.28; H, 6.41; N, 9.22. Found: C, 63.06; H, 5.97; N, 8.94.

EXAMPLE 17

N-1-4-(2-furanyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0638 Prepared in the same manner as example 16 substituting 2-(tributylstannyl) furan for tributyl(phenylethynyl)tin in examplel6D. 0639 1H NMR (300 MHz, d6-DMSO) 9.86 (s, 0.5H), 9.53 (s, 0.5H), 8.30 (s, 0.5H), 7.91 (s, 0.5H), 7.67-7.61 (m, 6H), 6.96-6.94 (m, 4H), 6.79-6.74 (d, 2H, J3.4 Hz), 6.55-6.54 (m, 2H), 4.80-4.60 (m, 0.5H), 4.45-4.30 (m, 0.5H), 4.17-3.98 (m, 6H), 3.76-3.70 (m, 2H), 3.62-3.56 (m, 2H), 2.79 (s, 6H), 1.28 (s, 12H); 0640 MS (ESI) m/e MH (402), MH (400), MNH4 (419); 0641 Anal. Calcd for: C2oH23N306: C, 59.84; H, 5.77; N, 10.46. Found: C, 59.83; H, 5.90; N, 10.12.

EXAMPLE 18

N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 18A

1-(4-butyloxy-1,1-biphenyl-4-yl)oxy)-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0642 To a warm (75) solution of example 16C (0.1 g, 0.27 mmol) and 4-butoxyphenylboronic acid (0.08 g, 0.41 mmol) in DME (2 mL) was added a 1M Na2CO3 solution (0.4 mL) followed by a catalytic amount of PdCl2(dppf). The reaction was held at 100 for 2 h, diluted with ethyl acetate (25 mL), washed with sat'd ammonium chloride, water, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (20% ethyl acetate in methylene chloride) gave 0.105 g of 5 as a white solid.

EXAMPLE 18B

N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0643 Prepared in the same manner as example 2D,E,F substituting 18A for 2C. 0644 1H NMR (300 MHz, d6-DMSO) 9.87 (s, 0.5H), 9.55 (s, 0.5H), 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.55-7.50 (m, 8H), 6.98-6.95 (m, 8H), 4.80-4.60 (m, 0.5H), 4.50-4.35 (m, 0.5H), 4.16-4.06 (m, 4H), 4.01-3.96 (t, 4H, J7.0, 5.9 Hz), 3.76-3.70 (m, 2H), 3.62-3.59 (m, 2H), 2.80 (s, 6H), 1.72-1.65 (m, 4H), 1.48-1.40 (m, 4H), 1.29 (s, 12H), 0.96-0.91 (t, 6H, J7.1, 7.5 Hz); 0645 MS (ESI) m/e MH (484), MNH4 (506); 0646 Anal. Calcd for: C26H33N3O6: C, 64.57; H, 6.87; N, 8.68. Found: C, 64.70; H, 7.04; N, 8.50.

EXAMPLE 19

N-1-(4-fluoro1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 19A

3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)-propan-1,2oxirane 0647 The title compound was prepared following the procedures described for example 5A and 5C, but using allyl alcohol in place of 3-buten-1-ol.

EXAMPLE 19B

N-1-(4-fluoro1,1 -biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0648 Prepared according to the sequence of reaction described in examples 5D through 5H, substituting 19A for 5C in example 5D and 4-(4-fluorophenyl)-phenol for 4-hydroxy-4-biphenyl carbonitrile in example 5F. 0649 1H NMR (300 MHz, d6-DMSO) 9.86 (S, 0.5H), 9.54 (S, 0.5H), 8.31 (S, 0.5H), 7.91 (S, 0.5H), 7.67-7.57 (M, 6H), 7.27-7.22 (M, 3H), 7.01-6.97 (M, 3H), 4.96-4.70 (M, 0.5H), 4.50-4.40 (M, 0.5H), 4.18-4.08 (M, 3H), 3.77-3.73 (M, 2H), 2.79 (S, 6H), 1.28 (S, 12H). 0650 MS (ESI) m/e 430 (MH), 428 (MH); 0651 Anal. Calcd for: C22H24N3O5F.0.5H2O: C, 60.26; H, 5.74; N, 9.58. Found: C, 60.48; H, 5.66; N, 8.72.

EXAMPLE 20

N-F1-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 0652 Prepared according to the sequence of reaction described in examples 5D through 5H, substituting 19A for 5C in example 5D and substituting 4-(4-Trifluoromethylphenyl)phenol for 4-hydroxy-4-biphenyl carbonitrile in example 5F. 0653 1H NMR (300 MHz, d6-DMSO) 9.80 (S, 0.5H), 9.58 (S, 0.5H), 8.32 (S, 0.5H), 7.92 (S, 0.5H), 7.87-7.84 (D, 4H, J8.1 Hz), 7.79-7.76 (D, 4H, J8.8 Hz), 7.72-7.69 (d, 4H, J8.4 Hz), 7.06-7.02 (m, 4H), 4.80-4.60 (m, 0.5H), 4.45-4.40 (m, 0.5H), 4.20-4.12 (m, 4H), 3.78-3.74 (m, 2H), 3.63-3.62 (m, 2H), 2.08 (s, 6H), 1.30 (s, 12H); 0654 MS (ESI) m/e MH (478), MH (480); 0655 Anal. Calcd for: C23H24N3O5F3.0.5H2O: C, 56.55; H, 5.15; N, 8.60. Found: C, 56.52; H, 5.07; N, 8.43.

EXAMPLE 21

N-1-(4-methoxy1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0656 Prepared according to the sequence of reaction described in examples 5D through 5H, substituting 19A for 5C in example 5D and substituting 4-(4-methoxyphenyl)phenol for 4-hydroxy-4-biphenyl carbonitrile in example 5F. 0657 1H NMR (300 MHz, d6-DMSO) 9.89 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.56-7.53 (d, 8H, J8.8 Hz), 7.01-6.94 (m, 8H), 4.80-4.60 (m, 0.5H), 4.44-4.35 (m, 0.5H), 4.17-3.95 (m, 4H), 3.74-3.71 (m, 2H), 3.63-3.58 (m, 2H), 2.79 (s, 6H), 1.28 (s, 12H); 0658 MS (ESI) m/e MH (442); 0659 Anal. Calcd for: C23H26N3O6.0.25H2O: C, 62.08; H, 6.00; N, 9.44. Found: C, 62.25; H, 6.30; N, 8.94.

EXAMPLE 22

N-1-(4-methyl1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0660 Prepared according to the sequence of reaction described in examples 5D through 5H, substituting 19A for 5C in example 5D and substituting 4-(4-methylphenyl)phenol for 4-hydroxy-4-biphenyl carbonitrile in example 5F. 0661 1H NMR (300 MHz, d6-DMSO) 9.89 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.92 (s, 0.5H), 7.59-7.56 (d, 4H, J8.8 Hz), 7.52-7.49 (d, 4H, J8.1 Hz), 7.24-7.22 (d, 4H, J7.7 Hz), 7.00-6.97 (m, 4H), 4.80-4.60 (m, 0.5H), 4.40-4.35 (m, 0.5H), 4.40-4.1 (m, 4H), 3.80-3.55 (m, 2H), 3.60-3.50 (m, 2H), 2.79 (s, 6H), 2.32 (s, 6H), 1.28 (s, 12H); 0662 MS (ESI) m/e 424 (MH), 426 (MH); 0663 Anal. Calcd for: C23H27N3O5.0.25H2O: C, 64.24; H, 6.44; N, 9.77. Found: C, 64.30; H, 6.55; N, 9.36.

EXAMPLE 23

N-1-(4-butoxyl 1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 23A

1-bromo-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)propan-2-one 0664 The title compound was prepared following the procedure desribed in examples 16A and 16 B, except substituting 5,5 dimethylhydantoin for 1,5,5 trimethylhydantoin in example 16A.

EXAMPLE 23B

N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0665 Prepared according to the procedures of example 16C and 16E, substituting example 23A for 16B and 4-(4-Butyloxyphenyl)phenol for 4-bromophenol in example 16C. 0666 1H NMR (300 MHz, d6-DMSO) 9.86 (s, 0.5H), 9.55 (s, 0.5H), 8.36 (s, 0.5H), 8.34 (s, 0.5H), 8.32 (s, 0.5H), 7.94 (s, 0.5H), 7.55-7.51 (m, 8H), 6.99-6.96 (m, 8H), 4.85-4.80 (m, 0.5H), 4.40-4.36 (m, 0.5H), 4.20-4.06 (mm, 2H), 4.01-3.97 (m, 4H), 3.78-3.71 (m, 2H), 3.60-3.51 (m, 2H), 1.73-1.66 (m, 6H), 1.48-1.38 (m, 4H), 1.25 (s, 12H), 0.96-0.86 (m, 6H); 0667 MS (ESI) m/e MH (468); 0668 Anal. Calcd for: C25H30N3O6: C, 63.95; H, 6.65; N, 8.94. Found: C, 63.89; H, 6.91; N, 8.63.

EXAMPLE 24

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-ethoxy1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 0669 Prepared according to the procedures of example 23B, except substituting 4-(4-ethoxyphenyl)phenol for 4-(4-Butyloxyphenyl)phenol. 0670 1H NMR (300 MHz, d6-DMSO) 9.84 (s, 0.5H), 9.52 (s, 0.5H), 8.37 (s, 0.5H), 8.32 (s, 2H), 7.92 (s, 0.5H), 7.55-7.52 (m, 8H), 6.98-6.95 (d, 4H, J8.8 Hz), 4.90-4.80 (m, 0.5H), 4.45-4.30 (m, 0.5H), 4.19-3.98 (m, 8H), 3.74-3.67 (m, 2H), 3.59-3.53 (m, 2H), 1.36-1.25 (m, 18H); 0671 MS (ESI) m/e MH (440), MH (442); 0672 Anal. Calcd for: C23H27N3O6.0.5H2O: C, 61.32; H, 6.26; N, 9.32. Found: C, 61.12; H, 6.35; N, 9.32.

EXAMPLE 25

N-1-4-(1,3-benzodioxol-5-yl)phenoxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0673 Prepared according to the procedures of example 23B, except substituting 4-(3,4-methylenedioxyphenyl)-phenol for 4-(4-Butyloxyphenyl)phenol. 0674 1H NMR (300 MHz, d6-DMSO) 9.84 (s, 0.5H), 9.52 (s, 0.5H), 8.37-8.31 (m, 3H), 7.91 (s, 0.5H), 7.55-7.52 (d, 4H, J8.5 Hz), 7.19 (s, 2H), 7.09-7.06 (m, 2H), 6.97-6.93 (d, 6H, J10.2 Hz), 6.03 (s, 4H), 4.70-4.60 (m, 0.5H), 4.45-4.30 (m, 0.5H), 4.16-3.96 (s, 6H), 3.73-3.57 (m, 5H), 1.27 (s, 12H); 0675 MS (ESI) m/e MH (442), MH (440); 0676 Anal. Calcd for: C22H23N3O7.0.50H2O: C, 58.66; H, 5.37; N, 9.32. Found: C, 58.70; H, 5.80; N, 8.79.

EXAMPLE 26

N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 26A

1-bromo-3-(3-methyl-2,5-dioxoimidazolidin-1-yl)propan-2-one 0677 The title compound was prepared following the procedure desribed in examples 16A and 16 B, except substituting 1-methylhydantoin for 1,5,5 trimethylhydantoin in example 16A.

EXAMPLE 26B

N-1-(4-butoxy1,1-biphenyl-4-yl)oxymethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0678 Prepared according to the procedures of example 16C and 16E, substituting example 26A for 16B and 4-(4-Butyloxyphenyl)phenol for 4-bromophenol in example 16C. 0679 1H NMR (300 MHz, d6-DMSO) 9.97 (s, 0.5H), 9.60 (s, 0.5H), 8.34 (s, 0.5H), 7.97 (s, 0.5H), 7.55-7.50 (m, 8H), 6.99-6.91 (m, 8H), 4.86-4.82 (m, 0.5H), 4.33-4.31 (m, 0.5H), 4.18-4.12 (m, 2H), 3.99-3.94 (m, 4H), 2.85 (s, 6H), 1.82-1.68 (m, 4H), 1.50-1.38 (m, 6H), 0.96-0.91 (m, 6H); 0680 MS (ESI) m/e MH (454); 0681 Anal. Calcd for: C24H29N3O6.0.25C4H5O: C, 63.51; H, 6.44; N, 8.88. Found: C, 63.59; H, 6.46; N, 8.68.

EXAMPLE 27

N-1-4-(3-thienyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0682 Prepared according to the procedures of example 16C and 16E, substituting 4-(4-(3-thienyl)phenyl)phenol for 4-bromophenol in example 16C. 0683 1H NMR (300 MHz, d6-DMSO) 9.90 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.75-7.74 (m, 2H), 7.67-7.60 (m, 6H), 7.52-7.49 (m, 2H), 6.96-6.92 (m, 4H), 4.80-4.6 (m, 0.5H), 4.50-4.4 (m, 0.5H), 4.19-3.98 (m, 6H), 3.81-3.70 (m, 2H), 3.61-3.56 (m, 2H), 2.79 (s, 6H), 1.29 (s, 12H); 0684 Anal. Calcd for: C20H23N3O5S: C, 57.54; H, 5.55; N, 10.06. Found: C, 57.72; H, 5.84; N, 9.76.

EXAMPLE 28

N-1-(1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0685 Prepared according to the procedures of example 16C and 16E, substituting 4-phenyl-phenol for 4-bromophenol in example 16C. 0686 1H NMR (300 MHz, d6-DMSO) 9.90 (S, 0.5H), 9.57 (S, 0.5H), 8.30 (S, 0.5H), 7.92 (S, 0.5H), 7.62-7.60 (D, 8H, J8.1 Hz), 7.45-7.40 (t, 4H, J5.8, 7.8 Hz), 7.33-7.28 (t, 2H, J7.1, 6.9 Hz), 7.02-6.97 (m, 4H), 4.80-4.60 (m, 0.5H), 4.45-4.40 (m, 0.5H), 4.18-4.01 (m, 4H), 3.77-3.70 (m, 2H), 3.63-3.6 (m, 2H), 2.80 (s, 6H), 1.28 (s, 12H); 0687 MS (ESI ) m/e MH (410), MH (412); 0688 Anal. Calcd for: C22H25N3O5.0.25H2O: C, 63.25; H, 6.17; N, 10.10. Found: C, 63.94; H, 6.41; N, 9.60.

EXAMPLE 29

N-1-(3-chloro-4-fluoro1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0689 Prepared according to the procedures of example 16C and 16E, substituting 4-(4-fluoro-3-chloro-phenyl)phenol for 4-bromophenol in example 16C. 0690 1H NMR (300 MHz, d6-DMSO) 9.90 (s, 0.5H), 9.57 (s, 0.5H), 8.31 (s, 0.5H), 7.92 (s, 0.5H), 7.84-7.82 (m, 2H), 7.65-7.61 (m, 6H), 7.49-7.43 (t, 2H, J9.2,8.8 Hz), 7.02-6.96 (m, 4H), 4.80-4.60 (m, 0.5H), 4.43-4.40 (m, 0.5H), 4.21-4.06 (m, 4H), 3.82-3.70 (m, 2H), 3.62-3.59 (m, 2H), 2.79 (s, 6H), 1.28 (s, 12H); 0691 MS (ESI) m/e MH (462), MH (464); 0692 Anal. Calcd for: C22H23N3O5ClF.0.25H2O: C, 56.41; H, 5.05; N, 8.97. Found: C, 56.78; H, 5.24; N, 8.55.

EXAMPLE 30

N-1-(2-methyl1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0693 Prepared according to the procedures of example 16C and 16E, substituting 4-(3-methyl-phenyl)phenol for 4-bromophenol in example 16C. 0694 1H NMR (300 MHz, d6-DMSO) 9.90 (s, 0.5H), 9.57 (s, 0.5H), 8.32 (s, 0.5H), 7.93 (s, 0.5H), 7.28-7.14 (mm, 12H), 6.99-6.64 (m, 4H), 4.90-4.80 (m, 0.5H), 4.42-4.40 (m, 0.5H), 4.22-4.04 (m, 6H), 3.82-3.74 (m, 2H), 3.62-3.58 (m, 2H), 2.80 (s, 6H), 2.20 (s, 6H), 1.29 (s, 12H); 0695 MS (ESI) m/e MH (426), MH (424); 0696 Anal. Calcd for: C23H27N3O5.0.25H2O: C, 64.24; H, 6.44; N, 9.77. Found: C, 64.50; H, 6.69; N, 9.31.

EXAMPLE 31

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 31A

3-(4-(4-Carbonitrilephenyl)phenoxy)-1-bromopropan-2-one 0697 The title compound was prepared according to the procedure described in examples 16A and 16B, but substituting 4-(4-cyanophenyl)-phenol for 1,5,5-trimethyl hydantoin in example 16A.

EXAMPLE 31B

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0698 Prepared according to the procedures of example 16C and 16E, substituting example 31A for 16B and hydantoin for 4-bromophenol in example 16C. 0699 1H NMR (300 MHz, DMSO-d6) 3.6-3.8 (m, 2H), 3.92 (d, 2H, J8.4 Hz), 4.10-4.25 (m, 2H), 4.3-4.4 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.0-7.1 (m, 2H), 7.74 (d, 2H, J9.0 Hz), 7.84 (d, 2H, J8.4 Hz), 7.89 (d, 2H, J8.4 Hz), 7.98 (s, 0.5H), 8.1-8.2 (m, 1H), 8.35 (s, 0.5H), 9.57 (br s, 0.5H), 9.53 (br s, 0.5H); 0700 MS (ESI) 395 (MH); 0701 Anal. Calcd for C20H18N4O5.0.2H2O.0.4EtOAc: C, 59.88; H, 5.03; N, 12.93. Found: C, 59.80; H, 4.81; N, 12.74.

EXAMPLE 32

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)ethyl-N-hydroxyformamide 0702 Prepared according to the procedures of example 16C and 16E, substituting example 31 A for 16B and saccharin for 4-bromophenol in example 16C. 0703 1H NMR (300 MHz, DMSO-d6) 3.9-4.2 (m, 2H), 4.2-4.3 (m, 2H), 4.45-4.55 (m, 0.5H), 5.0-5.1 (m, 0.5H), 7.0-7.1 (m, 2H), 7.74 (d, 2H, J8.4 Hz), 7.85 (d, 2H, J8.7 Hz), 7.88 (d, 2H, J8.4 Hz), 8.0-8.2 (m, 3.5H), 8.3-8.4 (m, 1.5H), 9.78 (s, 0.5H), 10.14 (s, 0.5H). MS (ESI) 476 (MH); 0704 Anal. Calcd for C24H19N3O6S.1.1H2O: C, 57.97; H, 4.30; N, 8.45. Found: C, 58.01; H, 3.96; N, 8.16.

EXAMPLE 33

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 0705 Prepared according to the procedures of example 23B, except substituting 4-(4-trifluoromethoxy phenyl)-phenol for 4-(4-Butyloxyphenyl)-phenol. 0706 1H NMR (300 MHz, DMSO-d6) 1.27 (s, 6H), 3.5-3.8 (m, 2H), 4.0-4.3 (m, 2H), 4.4-4.5 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.0-7.2 (m, 2H), 7.42 (d, 2H, J7.8 Hz), 7.64 (d, 2H, J8.4 Hz), 7.75 (d, 2H, J8.7 Hz), 7.93 (s, 0.5H), 8.33 (s, 0.5H), 8.35 (s, 0.5H), 8.40 (s, 0.5H), 9.56 (s, 0.5H), 9.87 (s, 0.5H); 0707 MS (ESI) 482 (MH); 0708 Anal. Calcd for C22H21N3O6F3: C, 54.88; H, 4.60; N, 8.72. Found: C, 55.22; H, 4.87; N, 8.36.

EXAMPLE 34

N-1-4-(4-phenyl-1-piperidinyl)phenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0709 Prepared according to the procedures of example 16C and 16E, substituting the 4-phenyl-N-phenyl piperidine (prepared as in Warner-Lambert patent WO 97/19068), for 4-bromophenol in example 16C. 0710 1H NMR (300 MHz, DMSO-d6) 1.27 (s, 3H), 1.28 (s, 3H), 1.7-1.9 (m, 4H), 2.55-2.75 (m, 3H), 2.78 (s, 1.5H), 2.79 (s, 1.5H), 3.5-3.8 (m, 4H), 3.9-4.1 (m, 2H), 4.3-4.4 (m, 0.5H), 4.7-4.8 (m, 0.5H), 6.81 (d, 2H, J8.7 Hz), 6.93 (d, 2H, J9.0 Hz), 7.15-7.25 (m, 1H), 7.25-7.35 (m, 4H), 7.89 (s, 0.5H), 8.30 (s, 0.5H), 9.54 (s, 0.5H), 9.86 (s, 0.5H); 0711 MS (ESI) 495 (MH); 0712 Anal. Calcd for C27H34N4O5: C, 65.56; H, 6.92; N, 11.32. Found: C, 65.35; H, 7.24; N, 10.93.

EXAMPLE 35

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 0713 Prepared according to the procedures of example 23B, except substituting 4-(4-trifluoromethylphenyl)phenol for 4-(4-Butyloxyphenyl)phenol. 0714 1H NMR (300 MHz, DMSO-d6) 1.28 (s, 6H), 3.5-3.8 (m, 2H), 4.1-4.3 (m, 2H), 4.4-4.5 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.0-7.2 (m, 2H), 7.72 (d, 2H, J8.4 Hz), 7.78 (d, 2H, J8.4 Hz), 7.86 (d, 2H, J8.4 Hz), 7.93 (s, 0.5H), 8.33 (s, 0.5H), 8.35 (s, 0.5H), 8.40 (s, 0.5H), 9.56 (s, 0.5H), 9.87 (s, 0.5H); 0715 MS (ESI) 466 (MH); 0716 Anal. Calcd for C22H22N3O5F3.0.6H2O: C, 55.49; H, 4.91; N, 8.82. Found: C, 55.55; H, 4.66; N, 8.77.

EXAMPLE 36

N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-methyl(4-methylphenyl)sulfonylaminoethyl-N-hydroxyformamide 0717 Prepared according to the procedures of example 16C and 16E, substituting example 31 A for 16B and N-methyl-(p-tolyl)sulfonamide for 4-bromophenol in example 16C. 0718 1H NMR (300 MHz, DMSO-d6) 2.41 (s, 3H), 2.70 (s, 1.5H), 2.73 (s, 1.5H), 3.05-3.35 (m, 2H), 4.0-4.2 (m, 2H), 4.3-4.4 (m, 0.5H), 4.8-4.9 (m, 0.5H), 7.06 (d, 2H, J8.7 Hz), 7.46 (d, 2H, J8.1 Hz), 7.65-7.8 (m, 4H), 7.85 (d, 2H, J8.7 Hz), 7.89 (d, 2H, J8.7 Hz), 8.04 (s, 0.5H), 8.40 (s, 0.5H), 9.71 (s, 0.5H), 10.0 (s, 0.5H); 0719 MS (ESI) 480 (MH); 0720 Anal. Calcd for C25H25N3O5S: C, 62.61; H, 5.25; N, 8.76. Found: C, 62.52; H, 5.27; N, 7.98.

EXAMPLE 37

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-4,4-dimethy-2,5-dioxo-3-(3-pyridinylmethyl)-1-imidazolidinylethyl-N-hydroxyformamide

EXAMPLE 37A

3-(3-pyridinylmethyl))-2,5-dioxo-4,4-dimethylimidazolidine 0721 The title compound was prepared following the prosedures described in examples 68A, 68B and 69B, except substituting 3-picolyl chloride for methyl iodide in example 68B.

EXAMPLE 37B

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-4,4-dimethy-2,5-dioxo-3-(3-pyridinylmethyl)-1-imidazolidinylethyl-N-hydroxyformamide 0722 The title compound was prepared according to the procedures of example 16C and 16E, substituting example 31A for 16B and 37A for 4-bromophenol in example 16C. 0723 1H NMR (300 MHz, DMSO-d6) 1.25 (s, 6H), 3.6-3.7 (m, 1H), 3.8-3.9 (m, 1H), 4.1-4.3 (m, 2H), 4.4-4.5 (m, 0.5H), 4.56 (s, 2H), 4.85-4.95 (m, 0.5H), 7.0-7.1 (m, 2H), 7.35 (dd, 1H, J8.1,4.8 Hz), 7.7-7.8 (m, 3H), 7.86 (d, 2H, J8.4 Hz), 7.90 (d, 2H, J8.4 Hz), 7.96 (s, 0.5H), 8.34 (s, 0.5H), 8.45-8.50 (narrow m, 1H), 8.60 (s, 1H), 9.64 (s, 0.5H), 9.97 (s, 0.5H); 0724 MS (ESI ()) 514 (MH); 0725 Anal. Calcd for C28H27N5O5.1.7H2O: C, 61.80; H, 5.63; N, 12.87. Found: C, 61.77; H, 5.08; N, 12.48.

EXAMPLE 38

N-2-(4-cyano1,1 -biphenyl-4-yl)oxy-1-methylpropyl-N-hydroxyformamide 0726 The title compound was prepared according to the procedures of example 16C and 16E, substituting 3-bromo-2-butanone for 16B and 4-(4-cyanophenyl)phenol for 4-bromophenol in example 16C. 0727 1H NMR (300 MHz, DMSO-d6) 1.1-1.3 (m, 6H), 3.8-4.0 (m, 1H), 4.3-4.7 (m, 1H), 7.0-7.1 (m, 2H), 7.6-7.7 (m, 2H), 7.8-7.9 (m, 4H), 8.02 (s, 0.5H), 8.28 (s, 0.25H), 8.33 (s, 0.25H), 9.43 (s, 0.25H), 9.60 (s, 0.25H), 9.85 (s, 0.25H), 9.95 (s, 0.25H). MS (ESI) 311 (MH). Anal. Calcd for C18H18N2O3.0.2H2O: C, 68.86; H, 5.91; N, 8.92. Found: C, 68.73; H, 5.79; N, 8.58.

EXAMPLE 39

N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 39A

3-cyano-4-hydroxy Biphenyl 0728 A 250 mL flask was charged with 2.21 g (2.7 mmol) 1,1-Bis(diphenylphosphino) ferrocene dichloropalladium (II).CH2Cl2 and 6.26 g (2.73 mmol) 3-iodobenzonitrile, 6.Og (3.95 mmol) 4-methoxyphenylboronic acid and 12.45 g (8.20 mmol) cesium fluoride added as solids followed by addition of 180 mL 1,2-dimethoxyethane. The flask was flushed with N2 and the suspension heated to reflux which was maintained for 3 hours. the cooled reaction mixture was filtered through a pad of 300 g flash silica gel and the pad was washed with 1L ethyl acetate. The ethyl acetate was concentrated and the residue purified by flash chromatography eluting with 10% hexanes/90% ethyl acetate to give 3.3 g of the desired product (58% yield). This material was dissolved in 50 mL anhydrous CH2Cl2 and the solution cooled in a dry ice-acetone bath and a solution of boron tribromide (40 mL, 4 mmol) was added dropwise under inert atmosphere. The reaction solution was then stirred at room temperature overnight. The reaction solution was cooled in an ice bath and 5 mL of H2O added dropwise followed by the addition of 20 mL 1N HCl. The mixture was stirred for 1 hour and the resulting suspension was filtered and the filtrate transferred to a separatory funnel and the organic layer separated off and set aside. the filtered solid was washed with H2O and ethyl acetate and filtered and the filtrate transferred to the separatory funnel and the organic layer combined with the previous organic layer, dried over Na2SO4, filtered and the filtrate concentrated to a 3.05 g of a white solid (99% yield).

EXAMPLE 39B

N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0729 Prepared according to the procedures of example 16C and 16E, substituting 3-cyano-4-hydroxy biphenyl for 4-bromophenol in example 16C. mp: 130-132 C.; 0730 1H NMR (DMSO-66) 9.86 (s, 1/2H), 9.48-9.63 (c, 1/2H), 8.33 (s, 1/2H), 8.09 (s, 1H), 7.97 (d, 1H, J4.5 Hz), 7.93 (s, 1/2H), 7.75 (d, 1H, J4.5 Hz), 7.70 (d, 2H, J6.0 Hz), 7.63 (t, 1H, J4.5 Hz), 7.00-7.07 (c, 2H), 4.83-4.90 (c, 1/2H), 4.60-4.67 (c, 1/2H); 0731 ESI(): 409 (M27), 437 (MH), 454 (MNH4), 459 (MNa); 0732 Anal. Calcd for: C23H24N4O5.0.25C4H8O2: C, 62.87; H, 5.71; N, 12.21. Found: C, 62.68; H, 5.55; N, 12.27.

EXAMPLE 40

N-1-4-(methylthio)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0733 Prepared according to the procedures of example 16C and 16E, substituting 4-thiomethyl-4-hydroxy biphenyl for 4-bromophenol in example 16C. 0734 mp 172-174. 0735 1H NMR (DMSO-6) 9.48-9.96 (BS, 1H), 8.34 (S, 1/2H), 7.94 (S, 1/2H), 7.54-7.63 (C, 4H), 7.29-7.34 (C, 2H), 6.97-7.03 (C, 2H), 4.82-4.92 (C, 1/2H), 4.39-4.47 (C, 1/2H), 4.07-4.25 (C, 2H), 3.73-3.85 (C, 1H), 3.59-3.68 (C, 1H), 2.80 (S, 1.5H), 2.79 (S, 1.5H) 0736 MS (ESI()) 456 ((MH)), 913 ((2MH)) Calcd: 458.175 Found: 458.1747; 0737 Anal. Calcd for: C23H27N305S C, 60.37; H, 5.95; N, 9.19;S;7.01 Found: C,60.29; H, 5.82; N, 9.08;S;6.98.

EXAMPLE 41

N-1-4-4-(trifluoromethyl)phenoxyphenoxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0738 Prepared according to the procedures of example 16C and 16E, substituting 4-(4-trifluoromethylphenoxy)phenol for 4-bromophenol in example 16C. 0739 mp 121-123 0740 1H NMR (DMSO-6) 9.46-9.97 (C, 1H), 8.33 (S, 1/2H), 7.94 (S, 1/2H), 7.71 (S, 1H), 7.69 (S, 1H), 7.04-7.14 (C, 4H), 6.97-7.03 (C, 2H), 4.81-4.91 (C, 1/2H), 4.39-4.47 (C, 1/2H), 4.14-4.22 (C, 1H), 4.04-4.13 (C, 1H), 2.81 (S, 1.5H), 2.80 (S, 1.5H), 1.30 (S, 1.5H); 0741 MS (ESI()) 494 (MH), 530 (MCl), 989 (2MH), 1011 (2MNa2H) Calcd: 496.169, 0742 Found: 496.1696; 0743 Anal. Calcd for: C23H24F3N3O6 Theory: C, 55.75; H, 4.88; N, 8.48;F,11.50. Found: C, 55.68; H, 4.92; N, 8.40;F, 11.24.

EXAMPLE 42

N-1-4-(trifluoromethoxy)1,1 -biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-2-N-hydroxyformamide 0744 Prepared according to the procedures of example 16C and 16E, substituting 4-trifluoromethoxy-4-hydroxy biphenyl for 4-bromophenol in example 16C. mp 129.3-130 C.; 0745 1H NMR, 400 Mz (DMSO-d6): 9.46-9.84 (c, 1/2H), 8.26 (s, 1/2H), 7.87 (s, 1/2H), 7.67 (s, 1H), 7.65 (s, 1H), 7.57 (s, 1H), 7.55 (s, 1H), 7.34 (s, 1H), 7.32 (s, 1H), 6.94-6.97 (c, 2H), 4.78-4.82 (c, 1/2H), 4.34-4.38 (c, 1/2H), 4.02-4.17 (c, 2H), 3.67-3.77 (c, 1H), 3.53-3.60 (c, 1H), 2.73 (s, 1.5H), 2.72 (s, 1.5H), 1.22 (s, 3H), 1.21 (s, 3H); 0746 MS (ESI()): 494 (MH), 530 (MCl), 989 (2MH), 1011 (2MNa-2H) Calcd.: 496.1695 Found: 496.1680; 0747 Anal. Calcd. for C23H24F3N3O6 Theory: C, 55.75; H, 4.88; N, 8.48; F, 11.50. Found: C, 55.69; H, 4.94; N, 8.23; F, 11.71.

EXAMPLE 43

N-1-4-(methylsulfonyl)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0748 Prepared according to the procedures of example 48A, 48B and 48C, substituting 16B for 23A for 4-bromophenol in example 48A. mp 174-175 C.; 0749 1H NMR, 400 MHz (DMSO-d6): 9.47-9.98 (c, 1H), 8.35 (s, 1/2H), 7.92-8.00 (c, 4.5H), 7.77 (s, 1H), 7.75 (s, 1H), 7.07-7.10 (c, 2H), 4.85-4.94 (c, 1/2H), 4.42-4.50 (1/2H), 4.13-4.30 (c, 2H), 3.76-3.86 (c, 1H), 3.63-3.69 (c, 1H), 3.39 (s, 3H), 2.83 (s, 1.5H), 2.82 (s, 1.5H), 1.32 (s, 3H), 1.31 (s,3H); 0750 MS ESI(): 488(MH), 977(2MH), 999(2MNa2H) 0751 ESI(): 490 (MH), 507 (MNH4), 512 (MNa); 0752 Anal. calcd. for C23H28.5N3O7.75S: Theory: C, 54.91; H, 5.71; N, 8.35;S, 6.37 Found: C, 54.85; H, 5.76; N, 8.00; S, 6.31.

EXAMPLE 44

N-1-3-(cyanomethyll)-4-methoxyl1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0753 Prepared according to the procedures of example 16C and 16E, substituting 4-(3-cyanomethyl-4-methoxyphenyl)phenol for 4-bromophenol in example 16C. 0754 1H NMR (300 MHz, DMSO-d6) 1.275, 1.290 (6H), 2.788, 2.800 (3H), 3.566-3.641 (m, 1H), 3.708-3.821 (m, 1H), 4.047-4.214 (m, 2H), 4.399-4.416 (m, 0.5H), 4.846 (m, 0.5H), 6.973-7.013 (2H), 7.110-7.140 (1H), 7.543-7.608 (m, 4H), 7.291 (s, 0.5H), 8.319 (s, 0.5H), 9.576 (s, 0.5H), 9.904 (s, 0.5H); 0755 MS (ESI) m/e 481 (MH), 498 (MNH4), 479 (MH); 0756 Anal. calcd for C25H28N4O6.0.5MeOH: C, 61.68; H, 6.08; N, 11.28. Found: C, 62.07; H, 6.21; N, 10.91.

EXAMPLE 45

N-1-3-(cyanomethyl)1,1-biphenyl-4-yloxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 0757 The title compouns was prepared according to the procedures of example 5, except avoiding the methylation step in example 5B and substituting 4-(3-cyanomethylphenyl)phenol for 4-hydroxy-4-biphenylcarbonitrile in example 5F . 0758 1H NMR (300 MHz, DMSO-d6) 1.27 (s, 6H), 1.70-2.00 (m, 2H), 3.37-3.47 (m, 2H), 3.96-4.08 (sm, 5H), 7.00-7.03 (d, 2H, 8.4 Hz), 7.28-7.31 (d, 1H, 8.7 Hz), 7.426-7.477 (t, 1H, 7.5 Hz), 7.56-7.61 (m, 4H), 7.915 (s, 0.73H), 8.28-8.34 (1.27H), 9.55 (s, 0.75H), 9.96 (s, 0.25H); 0759 MS (ESI) m/e 451 (MH), 468 (MNH4), 449 (MH); 0760 Anal. calcd for C25H28N4O6.MeOH: C, 62.22; H, 6.26; N, 11.61. Found: C, 62.25; H, 5.95; N, 11.57.

EXAMPLE 46

N-1-(4-butoxy 1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 46A

1-(4-bromophenylthio)-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0761 A solution of 4-bromothiophenol (2.15 g, 11.4 mmol) in DMF (50 mL) at ambient temperature was treated with cesium carbonate (5.57 g, 17.1 mmol) for 20 minutes, treated in a single portion with example 23A (2.5 g, 9.5 mmol), stirred for 1 hours at ambient temperature and diluted with water, extracted with ethyl acetate, the combined extracts were washed with water and brine, dried (Na2SO4), filtered, concentrated and purified on silica gel with 20 to 35 to 50% ethyl acetate/hexane to provide 3.17 g (90%) of the titled compound as a white solid. 0762 MS (APCI) m/e 371, 373 (MH), 388, 390 (MNH4), 369, 371 (MH), 405, 407 (MCl).

EXAMPLE 46B

1-(4-butoxyl1,1-biphenyl-4-yl)thiol-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0763 A solution of example 46A (700 mg, 1.89 mmol) in DME (20 mL) at ambient temperature was treated with 4-n-butoxybenzeneboronic acid (549 mg, 2.83 mmol), tetrakis-(triphenylphosphine)-palladium (218 mg, 0.189 mmol) and 1M sodium carbonate (3.54 mL, 3.54 mmol), the reaction vessel was sealed and heated at 90 C. for 6 hours, diluted with ethyl acetate, washed with sequentially saturated ammonium chloride solution, water and brine, dried (Na2SO4), filtered, concentrated and purified on silica gel with 30 to 50% ethyl acetate/dichloromethane to provide 650 mg (78%) of the title compound as a yellow solid. 0764 MS (APCI) m/e 441 (MH), 458 (MNH4)439 (MH), 475 (MCl).

EXAMPLE 46C

N-1-(4-butoxy1,1-biphenyl-4-yl)thiomethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0765 The title compound was prepared from 46B following the procedures described in example 2D, 2E, 2F. 0766 1H NMR (300 MHz, DMSO-d6) 0.919-0.967 (t, 3H, J7.2 Hz), 1.225-1.237(ss, 6H), 1.389-1.512(m, 2H), 1.666-1.760(m, 2H), 3.110-3.192(m, 2H), 3.528-3.735 (m, 2H), 3.987-4.030(t, 2H, J6.3 Hz), 4.030(m, 0.5H), 4.750(m, 0.5H),6.991-7.020 (d, 2H, J9 Hz), 7.383-7.417 (dd, 2H, J1.8, 8.4 Hz), 7.561-7.601 (4H), (1.5H), 9.56 (s, 7.767(s, 0.5H), 8.299(s, 1H), 8.337(s, 0.5H), 9.457(br s, 0.5H), 9.695(br s, 0.5H); 0767 MS (ESI) m/e 484 (MH); 0768 High resolution MS(FAB) Calc. m/z for m.485.1984, observed m/z 485.1980.

EXAMPLE 46D

N-1-(4-butoxy1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0769 A solution of example 46C (127 mg, 0.262 mmol) in methanol (2 mL), and PH 7 buffer (1 mL) at 0 C. was treated with oxone (402 mg, 0.655 mmol) for 30 minutes then ambient temperature for 1 hour, neutralized with saturated sodium bicarbonate, extracted with dichloromethane, combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The crude mixture was purified on silica gel with 50% ethyl acetate/hexane then 10% methanol/dichloromethane to provide 82 mg (60%) of the title compound as an white solid. 0770 1H NMR (300 MHz, DMSO-d6) ; 0.92-0.97 (t, 3H, 7.5 Hz), 1.20, 1.22 (ss, 6H), 1.42-1.52 (m, 2H), 1.68-1.77 (m, 2H), 3.41-3.72 (m, 3.5H), 4.02-4.06 (t, 2H, 6.6 Hz), 4.52 (m, 0.5H), 4.89 (m, 0.5H), 7.05-7.08 (d, 2H, 8.4 Hz), 7.70-7.74 (2H),7.91 (s, 3.5H), 8.10 (s, 0.5H), 8.32-8.35 (d, 1H, 9.6 Hz), 9.48 (s, 0.5H), 9.62 (s, 0.5H); 0771 MS (ESI) m/e 518 (MH), 535 (MNH4), 516 (MH), 552 (MCl); 0772 Anal. calcd for C25H28N4O6.0.25H2O: C, 57.51; H, 6.08; N, 8.04. Found: C, 57.78; H, 6.18; N, 7.84.

EXAMPLE 47

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide

EXAMPLE 47A

1-bromo-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butan-2-one 0773 To a suspension of CuBr2 (1.91 g, 8.5 mmol) and lithium bromide (1.48 g, 17 mmol) in THF (10 mL) was added a solution of 1.06 g (5.3 mmol) of 1-((1,2Oxiranyl)propyl-4,4-dimethyl-2,5-dioxoimidazolidine (prepared from example 5A following the procedure of example 5C) in 15 mL of THF. The reaction mixture was stirred for 2 h at room temperature, then partitioned between ethyl acetate and ph 7 buffer. The organic extract was washed with brine, dried and concentrated. The residue was filtered through a plug of silice eluting with ethyl acetate, and the filtrate was concentrated toi give a white solid, whic was dissolved in acetone (25 mL), cooled to 0 C., then treated with 2.5 mL of 8M Jones reagent and stirred at room temperature for 3h. The reaction was quenched with 2 mL isopropanol, then partitioned between ethyl acetate and water. The organic extract was washed with brine, dried, filtered, and concentrated. The residue was filtered through a plug of silice eluting with ethyl acetate, and the filtrate was concentrated to give the title compound.

EXAMPLE 47B

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 0774 The title compound was prepared according to the procedures of example 16C and 16E, exept substituting 47A for 16B and 4-hydroxy-4-biphenylcarbonitrile for 4-bromophenol in example 16C. 0775 mp 202-204 C.; 0776 1H NMR (300 MHz, DMSO-d6) ; 1.272 (6H), 1.70-2.00 (m, 2H), 3.38-3.46 (t, 2H, J6 Hz), 3.92-4.18 (m, 2.5H), 4.46-4.57 (m, 0.5H), 7.03-7.06 (d, 2H, J8.7 Hz), 7.695-7.724 (d, 2H, J8.7 Hz), 7.82-7.92 (m, 6.5H), 8.26-8.35 (1.5H), 9.75(s), 9.96 (s, 1H); 0777 MS (ESI) m/e 437 (MH), 454 (MNH4), 459 (MH); 0778 Anal. calcd for C25H28N4O6.0.25H2O: C, 62.64; H, 5.60; N, 12.70. Found: C, 62.55; H, 5.47; N, 12.65

EXAMPLE 48

N-1-4-(methylsulfonyll)1,1-biphenyl-4-ylloxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 48A

1-(4-(thiomethyl)1,1-biphenyl-4-yl)oxy)-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0779 A solution of 4-hydroxy-4-biphenylmethylsulfide (1.18 g, 5.47 mmol) in DMF (25 mL) at ambient temperature was treated with cesium carbonate (2.23 g, 6.84 mmol) for 20 minutes, treated in a single portion with 23A (1.2 g, 4.56 mmol), stirred for 2 hours at ambient temperature and diluted with water, extracted with ethyl acetate, the combined extracts were washed with water and brine, dried (Na2SO4), filtered, concentrated and purified on silica gel with 50 to 80% ethyl acetate/hexane to provide 1.0 g (55%) of the title compound as a white solid. 0780 MS (APCI) m/e 399 (MH), 416 (MNH4), 397 (MH), 433 (MCl).

EXAMPLE 48B

N-1-4-(thiomethyl)1,1-biphenyl-4-yloxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0781 The title compound was prepared from 48A following the procedures described in example 2D, 2E, 2F. 0782 MS (ESI) m/e 444 (MH), 461 (MNH4), 466 (MNa), 442 (MH).

EXAMPLE 48C

N-1-4-(methylsulfonyll)1,1-biphenyl-4-yloxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0783 A solution of example 48B (440 mg, 0.993 mmol) in methanol (100 mL) and water (50 mL) at 0 C. was treated with oxone (1.27 g, 2.06 mmol) and sodium bicarbonate (174 mg, 2.06 mmol) for 1 hour then ambient temperature for 1.5 hour, diluted with water, extracted with dichloromethane, combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The crude mixture was purified on silica gel with 80% ethyl acetate/hexane then 10% methanol/dichloromethane then recrystallized from dichloromethane/hexane to provide 375 mg (79%) of the title compound as an off-white solid. 0784 1H NMR (300 MHz, DMSO-d6) ; 1.26-1.27 (ss, 6H), 3.24 (s, 3H), 3.53-3.80 (m, 2H), 4.08-4.24 (m, 2H), 4.37-4.48 (m, 0.5H), 4.80-4.92 (m, 0.5H), 7.04-7.08 (dd, 2H, J3, 8.4 Hz), 7.72-7.75 (d, 2H, J8.7 Hz), 7.89-8.00 (4.5H), 8.33-8.40 (1.5H), 9.56 (s, 0.5H), 9.88 (s, 0.5H); 0785 MS (ESI) m/e 476 (MH), 493(MNH4), 474 (MH), 510 (MCl).

EXAMPLE 49

N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 49A

1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(2,5-dioxopyrrolidin-1-yl)-2-propanone 0786 The title compound was prepared as in Example 3C, except using potassium succinimide (0.10 g, 0.95 mmol) in place of potassium phthalimide. Purification by trituration with ethyl acetate provided 0.19 g (68%) of the title compound as a white solid. 0787 MS (APCI) m/e 383 (MCl).

EXAMPLE 49B

( )-1-(4-Cyano-1,1-biphenyl-4-yl)oxy)-3-(2,5-dioxopyrrolidin-1-yl)-prop-2-ylhydroxylamine 0788 The title compound was prepared from 49A using the procedure described in Example 2D and 2E.

EXAMPLE 49C

N-1-(3-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide 0789 The title compound was prepared from 49B using the procedure described in Example 2F. 0790 mp 128 C.; 0791 1H NMR (300 MHz, d6-DMSO) 10.01 (s, 0.5H), 9.63 (s, 0.5H), 8.34 (s, 0.5H), 7.98 (s, 0.5H), 7.90-7.82 (m, 4H), 7.73 (d, 2H, J8.8 Hz), 7.06-6.89 (m, 2H), 4.90-4.78 (m, 0.5H), 4.37-4.24 (m, 0.5H), 4.22-4.04 (m, 2H), 3.74-3.60 (m, 2H), 2.65-2.61 (m, 4H); 0792 MS (ESI) m/e 394 (MH), 411 (MNH4), 392 (M1); 0793 Anal. Calcd for: C21H19N3O5.H2O: C, 61.30; H, 5.14; N, 10.2 1. Found: C, 61.20; H, 5.03; N, 10.03.

EXAMPLE 50

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethyl-2,6-dioxo-1-piperidinyl)ethyl-N-hydroxyformamide 0794 The title compound was prepared as in Example 49, except using potassium-3,3-dimethylglutarimide (0.16 g, 1.1 mmol) in place of potassium succinimide. mp 121 C.; 0795 1H NMR (d6-DMSO) 9.88-9.78 (s, 0.5H), 9.60-9.52 (s, 0.5H), 8.31 (s, 0.5H), 7.95 (s, 0.5H), 7.90-7.82 (m, 4H), 7.73 (d, 2H, J8.9 Hz), 7.02 (d, 2H, J8.8 Hz), 4.88-4.77 (s, 1H), 4.30-3.78 (m, 4H), 2.56 (s, 4H), 0.98 (s, 6H); 0796 MS (ESI) 436 (MH), 458 (MNa), 434 (MH).

EXAMPLES 51 AND 52

N-1S-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide

N-1R-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 51A AND 52A 0797 A solution of Example 49B (0.2 g, 0.55 mmol), D-Mannose diacetonide (0.13 g, 0.50 mmol), and acetic acid (0.03 mL, 0.50 mmol) in CHCl3 (5 mL) were heated at reflux for 16 h, cooled, and partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate. The organic layer was washed sequentially with water and brine, dried (MgSO4), filtered, and concentrated. Purification by HPLC provided the two enantiomers 51 A (31%) and 52A (16%).

EXAMPLE 51B 0798 A solution of 51A in MeOH (1 mL) and HCl (conc) (0.5 mL) was stirred at ambient temperature for 15 min, treated with saturated aqueous sodium bicarbonate, and partitioned between ethyl acetate and water. The organic layer was dried (MgSO4), filtered, and concentrated to provide 0.014 g (79%) of the corresponding hydroxyl amine, which was then formylated as in Example 2F.

EXAMPLE 52B 0799 The title compound was prepared according to Example 51B but using Example 52A in place of Example 51A.

EXAMPLE 53

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-3-methyl-2,5-dioxo-1-pyrrolidinyl)ethyl-N-hydroxyformamide 0800 The title compound was prepared as in Example 49, except using potassium-3-methyl-3-ethyl succinimide (0.22 g, 1.53 mmol) in place of potassium succinimide. 0801 1H NMR (d6-DMSO) 9.99-9.94 (br, 0.5H), 9.64-9.58 (br, 0.5H), 8.31 (d, 0.5H, J1.8 Hz), 7.93 (d, 0.5H, J2.9 Hz), 7.87 (q, 4H, J4.1 Hz), 7.74 (d, 2H, J8.9 Hz), 7.04 (dd, 2H, J8.8, 2.6 Hz), 4.93-4.81 (m, 0.5H), 4.44-4.33 (m, 0.5H), 4.24-4.05 (m, 2H), 3.85-3.71 (m, 1H), 3.62-3.53 (m, 1H), 2.69-2.38 (m, 2H), 1.64-1.46 (m, 2H), 1.18 (d, 3H, J4.4 Hz), 0.85-0.75 (m, 3H); 0802 MS (ESI) 436 (MH), 434 (MH), 458 (MNa), 453 (MNH4); 0803 Anal. Calcd for: C24H25N3O5: C, 66.19; H, 5.78; N, 9.64. Found: C, 66.07; H, 5.85; N, 9.37.

EXAMPLE 54

N-4-4-(4-chlorophenoxy)phenylsulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide

EXAMPLE 54A 0804 The title compound was prepared as in Example 2D but using 5,6-dihydro-2H-pyran-2-one (4.3 g, 43 mmol) in place of 1-(4-(4-carbonitrilephenyl)phenoxy)-3-thiophenoxypropan-2-one and O-Benzyl hydroxylamine in place of hydroxylamine to provide the corresponding oxime. Purification on silica gel with 1% methanol/dichloromethane provided 8.5 g (96%) of the title compound as a clear liquid. 0805 MS (ESI) 207 (MH)

EXAMPLE 54B

N-4-4-(4-chlorophenoxy)phenylsulfonylmethyltetrahydro-2H-pyran-4-yl-N-benzyloxy Amine 0806 To a solution of phenoxyphenyl-4-chloro-4-methylsulfone (0.76 g, 2.7 mmol) (preparation desribed in J. Med. Chem. 29, 427-433, 1986) at 78 C. was added n-BuLi (1.1 mL, 2.7 mmol). After stirring at 78 C. for 15 minures, BF3.OEt2 was added, followed by Example 54A. After 1 h, the reaction mixture was partitioned between with water and ethyl acetate, dried (MgSO4), filtered, and concentrated. Recrystallization with ethyl acetate provided 0.41 g (35%)of the desired compound as a white solid. 0807 MS (ESI) 488 (MH), 510 (MNa).

EXAMPLE 54C

N-4-4-(4-chlorophenoxy)phenylsulfonylmethyltetrahydro-2H-pyran-4-yl-N-benzyloxyformamide 0808 A solution of 54B (0.05 g, 0.10 mmol) in CH2Cl2 (2 mL) was treated with formic-p-methoxyphenyl anhydride, stirred at ambient temperature for 16 h, treated with H2O, and partitioned between ethyl acetate and brine. The organice layer was dried (MgSO4), filtered, and concentrated. Purification on silica gel with 10% ethyl acetate/dichloromethane provided 0.017 g (32%) of the desired compound as a white solid 0809 MS (ESI) 516 (MH), 533 (MNH4), 538 (MNa).

EXAMPLE 54D N-4-4-(4-chlorophenoxy)phenylsulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide 0810 A solution of 54C (0.017 g, 0.033 mmol) and Pd black (0.006 g) in dioxane (2 mL) and acetic acid (2 mL) was stirred under H2 for 20 min, treated with NaHCO3, partitioned between ethyl acetate and water. The organic layer was dried (MgSO4), filtered, and concentrated. Purification on silica gel with 2% MeOH/dichloromethane provided 0.002 g (14%) of the desired compound. 0811 1H NMR (d6-DMSO) 9.50-9.45 (br, 1H), 8.19 (s, 1H), 7.90-7.86 (m, 2H), 7.53-7.50 (m, 2H), 7.22-7.18 (m, 4H), 3.70-3.58 (m, 4H), 3.55-3.44 (m, 2H), 2.22-2.07 (m, 2H), 2.07-1.91 (m, 2H); 0812 MS (ESI) 424 (MH), 426 (MH), 448 (MNa).

EXAMPLE 55

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(2-methoxycarbonyl)phenyl-thioethyl-N-hydroxyformamide 0813 The title compound was prepared following the procedure from Example 2B, C, D, E, F but using methyl thiosalicylate (600 mg, 2.39 mmol) in place of thiophenol in example 2B. Mixture of two rotamers: 1H NMR (300 MHz, d6-DMSO) 10.11 (s, 1H), 9.73 (s, 1H), 8.41 (s, 1H), 7.95 (s, 1H), 7.90-7.83 (m, 10H), 7.75-7.71 (m, 4H), 7.59-7.55 (m, 4H), 7.31-7.26 (m, 2H), 7.09-7.05 (m, 4H), 4.75 (m, 1H), 4.2804.24 (m, 4H0, 4.18 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.31-3.18 (m, 4H); 0814 MS (ESI) m/e 463 (M1); 0815 Anal. calcd for C25H22N2O5S: C, 64.92; H, 4.79; N, 6.06. Found: C, 64.69; H, 4.63; N, 5.92.

EXAMPLE 56

N--(4-cyanol1,1-biphenyl-4-yl)oxymethyl-5-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxypentyl-N-hydroxyformamide

EXAMPLE 56A

6-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxyl-hex-1-ene 0816 The title compound was prepared following the procedure from Example 5A but using 6-hydroxy-4-methylcoumarin (500 mg, 2.84 mmol) in place of 5,5-dimethylhydantoin and 5-hexen-1-ol in place of 3-buten-1-ol. Purification on silica gel with 20% ethyl acetate/hexanes provided 560 mg (76%) of the title compound. 0817 1H NMR (300 MHz, d6-DMSO) 7.34 (dd, 1H), 7.24-7.20 (m, 2H), 6.40 (d, 1H), 5.90-5.77 (m, 1H), 5.04 (dq, 1H), 4.98 (dq, 1H), 4.06 (t, 2H), 2.43 (d, 3H), 2.10 (q, 2H), 1.75 (dt, 2H), 1.53 (dt, 2H).

EXAMPLE 56B

N-1-(4-cyanol1,1-biphenyl-4-yl)oxymethyl-5-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxypentyl-N-hydroxyformamide 0818 The title compound was prepared following the procedures from Example 5C, 1B, 2C, 2D, 2E and 2F but using 56A (500 mg, 1.94 mmol) in place of 5B in example 56B. Purification on silica gel with 50% ethyl acetate/hexanes provided 400 mg (75%) of the title compound. 0819 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.89 (s, 1H), 9.51 (s, 1H), 8.42 (s, 1H), 8.03 (s, 1H),7.86 (m, 8H), 7.73-7.70 (m, 4H), 7.34 (d, 2H), 7.24-7.21 (m, 4H), 7.08-7.04 (m, 4H), 6.40 (s, 2H), 4.60 (s, 1H), 4.18-3.99 (m, 9H), 2.43 (s, 6H), 1.86-1.54 (m, 12H); 0820 MS (ESI) m/e 513 (M1); 0821 Anal. calcd for C30H28N2O6: C, 70.30; H, 5.51; N, 5.47. Found: C, 70.52; H, 5.85; N, 5.20.

EXAMPLE 57

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-4-(4-methyl-2-oxo-2H-1-benzopyran-6-yl)oxybutyl-N-hydroxyformamide 0822 The title compound was prepared following the procedure from Example 56 but using 4-penten-1-ol in place of 5-hexen-1-ol in example 56A. 0823 Mixture of two rotamers: 1HNMR (300 MHZ, d6-DMSO) 69.94 (s, 1H), 9.55 (s, 1H0, 8.44 (s, 1H), 8.06 (s, 1H), 7.86 (m, 8H), 7.73-7.70 (m, 4H), 7.35 (d, 2H), 7.26-7.22 (m, 4H), 7.08-7/05 (m, 4H), 6.40 (s, 2H), 4.65 (m, 1H), 4.17-4.04 (m, 9H), 2.44 (s, 6H), 1.77 (m, 8H); 0824 MS (ESI) m/e 499 (M1); 0825 Anal. calcd for C29H26N2O6.0.75H2O: C, 68.03; H, 5.41; N, 5.47. Found: C, 68.21; H, 5.25; N, 5.28.

EXAMPLE 58

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-4-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxybutyl-N-hydroxyformamide 0826 The title compound was prepared following the procedure from Example 56 but using 7-hydroxy-4-methylcoumarin (500 mg, 2.8 mmol) in place of 6-hydroxy-4-methylcoumarin and 4-penten-1-ol in place of 5-hexen-1-ol in example 56A. Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.95 (s, 1H), 9.55 (s, 1H), 9.44 (s, 1H), 8.05 (s, 1H), 7.90-7.82 (m, 8H), 7.73-7.67 (m, 6H), 7.08-7.04 (m, 4H), 7.01-6.95 (m, 4H), 6.21 (s, 2H), 4.64 (m, 1H), 4.20-4.01 (m, 9H), 2.40 (s, 6H), 1.80-1.74 (m, 8H); 0827 MS (ESI) m/e 499 (M1); 0828 Anal. calcd for C29H26N2O6: C, 69.87; H, 5.26; N, 5.62. Found: C, 69.51; H, 5.33; N, 5.40.

EXAMPLE 59

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-5-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)oxypentyl-N-hydroxyformamide 0829 The title compound was prepared following the procedure from Example 56 but using 7-hydroxy-4-methylcoumarin (500 mg, 2.8 mmol) in place of 6-hydroxy-4-methylcoumarin in example 56A. 0830 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.89 (s, 1H0, 9.50 (s, 1H0, 8.42 (s, 1H), 8.03 (s, 1H), 7.90-7.82 (m, 8H), 7.73-7.66 (m, 6H), 7.08-7.03 (m, 4H), 6.98-6.94 (m, 2H0, 6.21 (s, 2H), 4.60 (m, 1H), 4.15-3.98 (m, 9H), 2.40 (s, 6H), 1.84-1.40 (m, 12H); 0831 MS (ESI) m/e 513 (M1); 0832 Anal. calcd for C30H28N2O6: C, 70.30; H, 5.51; N, 5.47. Found: C, 70.35; H, 5.52; N, 5.17.

EXAMPLE 60

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(5,5-dimethy-2,4-dioxo-3-oxazolidinyl)ethyl-N-hydroxyformamide 0833 The title compound was prepared as in Example 49, except using 5,5-dimethyloxazolidinine-2,4-dione (300 mg, 0.8 mmol) in place of succinimide. Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 10.08 (s, 1H), 9.70 (s, 1H), 8.35 (s, 1H), 7.98 (s, 1H), 7.90-7.83 (m, 8H), 7.74 (d, 4H), 7.06 (d, 4H), 4.90 (m, 1H), 4.47 (m, 1H), 4.24-4.16 (m, 4H), 3.85 (d, 1H), 3.80 (d, 1H), 3.69-3.65 (m, 1H), 3.64-3.61 (m, 1H), 1.49 (s, 6H), 1.48 (s, 6H); 0834 MS (ESI) m/e 441 (M18).

EXAMPLE 61

N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 61A

1-(4-cyano1,1-biphenyl-4-yl)thiol-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0835 A solution of 4-thiol-4-biphenylcarbonitrile (150 mg, 0.71 mmol) in 6 mL of DMF at 5 C. was treated with potassium carbonate (89 mg, 0.645 mmol) and 1-bromo-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidin-1-yl)-2-propanone (179 mg, 0.645 mmol), stirred 1 h at 5 C., quenched with saturated NH4Cl, extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated to a solid. Purification on silica gel with 1:1 ethyl acetate/hexanes provided 200 mg (75%) of the title compound. 0836 1H NMR (300 MHZ, d6-DMSO) 7.94-7.87 (m, 4H), 7.72 (d, 2H), 7.43 (d, 2H), 4.55 (s, 2H), 4.27 (s, 2H), 2.80 (s, 3H), 1.32 (s, 6H).

EXAMPLE 61B

N-1-(4-cyano1,1-biphenyl-4-yl)thiomethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0837 The title compound was prepared from 61A following the procedures from Example 2D, 2E and 2F. 0838 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.76 (s, 1H), 9.51 (s, 1H), 8.29 (s, 1H), 7.93-7.87 (m, 8H), 7.75-7.72 (m, 5H), 7.50-7.44 (m, 4H), 4.60 (m, 1H), 4.10 (m, 1H), 3.80-3.60 (m, 4H), 3.25-3.15 (m, 4H), 2.77 (s, 6H), 1.25 (s, 12H).

EXAMPLE 61C

N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0839 A solution of 61B (81 mg, 0.18 mmol) in 4:1 THF/H2O at 0 C. was treated with OXONE (140 mg) and NaHCO3 (33 mg), stirred at 0 C. for 30 min then 23 C. for 1 h, quenched with H2O, extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, and concentrated to a white solid. Purification on silica gel with 2% methanol/dichloromethane provided 43 mg (49%) of the title compound. 0840 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.71 (s, 1H), 9.54 (s, 1H), 8.09 (s, 1H), 8.07-7.96 (m, 16H), 7.74 (s, 1H), 4.90 (m, 1H), 4.54 (m, 1H), 3.74-3.60 (m, 4H), 3.55-3.44 (m, 4H), 2.74 (s, 3H), 2.74 (s, 3H), 1.24-1.22 (m, 12H); 0841 MS (ESI) m/e 485 (M1); 0842 Anal. calcd for C23H24N4O6S: C, 57.01; H, 4.99; N, 11.56. Found: C, 56.86; H, 5.21; N, 11.28.

EXAMPLE 62

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(3-methyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0843 The title compound was prepared as in Example 49, except using 1-methylhydantoin in place of succinimide. 0844 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.97 (s, 1H), 9.61 (s, 1H), 8.35 (s, 1H), 7.98 (s, 1H), 7.90-7.83 (m, 8H), 7.73 (d, 4H), 7.03 (d, 2H), 7.01 (d, 2H), 4.88-4.84 (m, 1H), 4.39-4.35 (m, 1H), 4.22-4.08 (m, 4H), 3.97 (s, 2H), 3.94 (s, 2H), 3.75-3.57 (m, 4H), 2.86 (s, 3H), 2.85 (s, 3H); 0845 MS (ESI) m/e 409 (M1); 0846 Anal. calcd for C21H20N4O5: C, 61.76; H, 4.94; N, 13.72. Found: C, 61.47; H, 5.00; N, 13.39.

EXAMPLE 63

N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0847 The title compound was prepared following the procedure from Example 61 but using 1-bromo-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidin-1-yl)-2-propanone in place of 1-bromo-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidin-1-yl)-2-propanone in example 61 A. 0848 Mixture of two rotamers: 1H NMR (300 MHZ, d6-DMSO) 9.66 (s, 1H0, 9.51 (s, 1H), 8.38 (s, 1H), 8.34 (s, 1H), 8.10 (s, 1H), 8.07-7.96 (s, 16H), 7.74 (s, 1H), 4.94-4.86 (m, 1H), 4.58-4.50 (m, 1H), 3.80-3.37 (m, 8H), 1.23-1.20 (m, 12H); 0849 MS (ESI) m/e 488 (M18); 0850 Anal. calcd for C22H22N4O6S: C, 56.16; H, 4.71; N, 11.91. Found: C, 56.12; H, 5.00; N, 11.59.

EXAMPLE 64

( )-N-1-(4-chloro-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 64A

1-4-chloro-1,1-biphenyl-4-yl)oxy-3-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1yl)-propan-2-one 0851 A solution of Example 16B (0.81 g, 2.93 mmol), 4-chloro-4-hydroxybiphenyl (0.50 g, 2.44 mmol), and potassium carbonate (0.35 g, 2.57 mmol) in dry DMF (50 mL) was stirred at ambient temperature for 1.5 hour and partitioned between ethyl acetate and water. The aqueous layer was drawn off and extracted with ethyl acetate (1). The combined organic extracts were diluted with an equal volume of hexanes and washed sequentially with water (3) and brine (2), dried (Na2SO4), filtered, and concentrated to provide 0.89 g of a waxy clumpy solid which was purified by purified on silica gel with 40% ethyl acetate/dichloromethane to provide 0.46 g (47%) of the title compound as a colorless solid. 0852 mp 165-166 C.; 0853 MS (DCI/NH3) m/e 379 (MNH4).

EXAMPLE 64B

( )-N-1-(4-chloro-1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0854 The ketone from Example 64B was sequentially converted to the corresponding oximes, hydroxylamine, and the final compound as described in Examples 2D, 2E, and 2F The title compound was purified on silica gel with 2.5% methanol/dichlormethane to provide the title compound as a colorless solid which was recrystallized from ethyl acetate/hexanes. 0855 mp 124-125 C.; 0856 MS (DCI/NH3) m/e 446 (MH) and 463 (MNH4); 0857 1H NMR (300 MHz, CDCl3) 9.90 (s; 0.5H), 9.58 (s; 0.5H), 8.32 (s; 0.5H), 7.92 (s; 0.5H), 7.65 (d; 2H; J9 Hz), 7.61 (d; 2H; J9 Hz), 7.47 (d; 2H; J9 Hz), 6.99 (d; 1H; J9 Hz), 6.97 (d; 1H; J9 Hz), 4.86 (m; 0.5H), 4.42 (m; 0.5H), 4.08-4.23 (m; 2H), 3.82-3.70 (m; 1H), 3.55-3.65 (m; 1H), 2.80 (s; 1.5H), 2.78 (s; 1.5H), 1.30 (s; 3H), 1.28 (s; 3H); 0858 Anal. calcd for C22H24N3O5Cl: C, 59.26; H, 5.42; N, 9.42. Found: C, 59.54; H, 5.61; N, 9.13.

EXAMPLE 65

()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide

EXAMPLE 65A

1-(3-(3-cyanomethyl-1,1-biphenyl-4-yl)oxy-propan-2-on-1-yl)-3,4,4-trimethyl-2,5-dioxoimidazolidine 0859 The title compound was prepared as in Example 5F but using 4-hydroxy-3-biphenylcarbonitrilemethane (0.95 g, 2.80 mmol) in place of 4-hydroxy-4-biphenylcarbonitrile. Purification on silica gel with 100% ethyl acetate provided 0.78 g of title compound. 0860 MS (DCI/NH3) m/e 437 (MNH4).

EXAMPLE 65B

()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 0861 Example 65A (0.78 g, 1.87 mmol) was processed sequentially according to the precedures in Example 2D, 2E, and 2F without purification of the intermediates. Purification on silica gel with 100% ethyl acetate provided 500 mg (1.08 mmol) of the title compound. 0862 1H NMR (300 MHz, DMSO) 9.99 (s, 0.5H), 9.58 (s, 0.5H), 8.36 (s, 0.5H), 7.92 (s, 0.5H), d 7.60 (m, 4H), 7.46 (t, 1H J8 Hz), 7.30 (d, 1H; J8 Hz), 7.02 (d, 2H; J8 Hz), 4.50 (m, 0.5H), 4.18 (m, 0.5H), 4.12 (s, 2H), 4.10 (m, 2H), 3.45 (m, 2H), 2.80 (s, 3H), 1.92 (m, 1H), 1.80 (m, 1H), 1.30 (s, 6H); 0863 MS (DCI/NH3) m/e 482 (MNH4).

EXAMPLE 66

()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-isopropylthioethyl-N-hydroxyformamide

EXAMPLE 66A

()-1-(4-cyano-1,1-biphenyl-4-y)oxy-3-isopropylthio-2-propanol 0864 A solution of isopropylthiol (0.48 g, 6.4 mmol ) in THF (20 mL) was treated with K2CO3 (0.5 g, 3.6 mmol). After 30 minutes, 3-(4-cyano-1,1-biphenyl-4-y)oxy-(1,2) oxirane (0.8 g, 3.19 mmol) was added in a single portion. The resulting solution was stirred at 70 C. for 3 hours, quenched by adding excess aqueous sodium bicarbonate solution and partitioned between ethyl acetate and brine. The organic layer was dried (Na2SO4), filtered, and the product was purified on silica gel with 50% ethyl acetate/hexanes to provide 0.9 g (2.75 mmol, 86% ) of the title compound. 0865 MS (DCI/NH3) m/e 345 (MNH4) and 362 (MNH4NH3).

EXAMPLE 66B

()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-isopropythioethyl-N-hydroxyformamide 0866 Example 66A was processed according to the procedures in Example 2C, 2D, 2E, and 2F providing the title compound as a light orange foam. 0867 1H NMR (300 MHz, DMSO) 9.99 (s: 0.5H), 9.60 (s: 0.5H), 8.42 (s: 0.5H), 8.04 (s: 0.5H), d 7.85 (m; 4H), 7.75 (d; 2H J9 Hz), 7.05 (d;2H; J9 Hz), 4.63 (m; 1H), 4.17 (m; 3H), 3.0 (m; 1H), 2.79 (m; 1H), 1.22 (dd; 6H; J7.50 Hz); 0868 MS (DCI/NH3) m/e 388 (MNH4).

EXAMPLE 67

()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 67A

()-1-4-(3-cyanoemethylphenyl)phenoxy-3-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)-2-propanol 0869 The title compound was prepared as in Example 4A but using 4-hydroxy-3-biphenylcarbonitrilemethane (170 mg, 0.64 mmol) and 3,5,5-trimethylhydantoin (37 mg, 0.96 mmol) in place of 4-hydroxy-4-biphenylcarbonitrile and 5,5-dimethylhydantoin. Purification on silica gel with 100% ethyl acetate provided 130 g of title compound. 0870 MS (DCI/NH3) m/e 415 (MNH4).

EXAMPLE 67B

()-N-1-(3-cyanomethyl-1,1-biphenyl-4-y)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0871 Example 67A was processed according to the procedures in Example 2C, 2D, 2E, and 2F providing the title compound. 0872 1H NMR (300 MHz, DMSO) 9.86 (s: 0.5H), 9.58 (s: 0.5H), 8.34 (s: 0.5H), 7.92 (s: 0.5H), d 7.60 (m; 4H), 7.46 (t; 1H J8 Hz), 7.30 (d; 1H; J8 Hz), 7.02 (d; 2H; J8 Hz), 4.85 (m; 0.5H), 4.42 (m; 0.5H), 4.10 (m; 2H), 4.12 (s; 2H), 3.68 (m; 1H), 3.62 (m; 1H), 2.80 (s; 3H), 1.30 (s: 6H); 0873 MS (DCI/NH3) m/e 468 (MNH4).

EXAMPLE 68 0874 ()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 68A

4,4-dimethyl-2,5-dioxo-N-(4-methoxoybenzyl)imidazolidine 0875 A solution of 4,4-dimethyl-2,5-dioxoimidazolidine (17.0 g, 133 mmol), 4-methoxybenzyl chloride (30.0 g, 192 mmol), and potassium carbonate (27.5 g, 200 mmol) in dry DMF (600 mL) was heated at 80 C. under nitrogen for 3h. The volume was reduced under high vacuum to about of the original volume and the resulting solution was partitioned between ethyl acetate and water. The aqueous layer was drawn off and extracted with ethyl acetate (2). The combined organic extracts were washed sequentially with water (2) and brine (2), dried (Na2SO4), filtered and concentrated under vacuum to provide 32.97 g of a solid. Pure title compound was obtained by recrystallization from ethyl acetate and hexanes to provide 24.5 g (74%) of a colorless solid. 0876 mp 109-111 C.; 0877 MS (DCI/NH3) m/e 249 (MH) and 266 (MNH4).

EXAMPLE 68B

3-Ethyl-1-(4-methoxybenzyl)-2,5-dioxo-4,4-dimethylimidazolidine 0878 A solution of 4,4-dimethyl-2,5-dioxo-N-(4-methoxoybenzyl)imidazolidine (3.5 g, 14.1 mmol) in THF (100 mL) was treated with sodium hydride (0.5 g, 21.2 mmol), stirred for 10 minute, treated with iodoethane (3.3 g, 21.2 mmol), stirred at 50 C. for 3 hours. then treated with HCl solution (10%) and partitioned between ethyl acetate and brine. The organic layer was dried, filtered and concentrated to provide 3.8 g (13.8 mmol, 98%) of title compound as white solid. 0879 MS (DCI/NH3) m/e 294 (MNH4).

EXAMPLE 68C

3-Ethyl-2,5-dioxo-4,4-dimethylimidazolidine 0880 A solution of 3-ethyl-1-(4-methoxybenzyl)-2,5-dioxo-4,4-dimethylimidazolidine (3.86 g, 14.0 mmol) in methoxybenzene (100 mL) was treated with alumiun trichloride (5.5 g, 42 mmol), stirred at 75 C. for 30 minute, then poured the reaction into HCl solution (10%) and partitioned between ethyl acetate and brine. The organic layer was dried, filtered, and concentrated. Purification by recrystalization with ethyl acetate provided 2.1 g (13.5 mmol, 96%) of title compound as white solid. 0881 MS (DCI/NH3) m/e 174 (MNH4).

EXAMPLE 68D

1-(4-cyano-1,1-biphenyl-4-y)oxy-3-(3-ethyl-5,5-dimethyl-2,4-dioxo-1-imidazolidinyl)-2-propanone 0882 A solution of 3-ethyl-2,5-dioxo-4,4-dimethylimidazolidine (0.7 g, 4.5 mmol) in DMF (100 mL) was treated with potassium carbonate (0.6 g, 4.5 mmol) and 1-(4-cyano-1,1-biphenyl-4-y)oxy-3-bromo-2-propynone (1.0 g, 3.0 mmol), stirred at 25 C. for 20 hours, then the reaction was poured into aqueous HCl solution (10%) and partitioned between ethyl acetate and brine. The organic layer was dried, filtered, and concentrated. Purification on silica gel with 50% ethyl acetate provided 0.8 g (1.97 mmol, 66%) of title compound as white solid. 0883 MS (DCI/NH3) m/e 424 (MNH4).

EXAMPLE 68E

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0884 Example 68B (0.72 g, 1.77 mmol) was processed sequentially according to the precedures in Example 2D, 2E, and 2F without purification of the intermediates. Purification on silica gel with 60% ethyl acetate/hexanes provided 158 mg (0.35 mmol) of the title compound. 0885 1H NMR (300 MHz, DMSO) 9.85 (s, 0.5H), 9.54 (s, 0.5H), 8.32 (s, 0.5H), 7.94 (s, 0.5H), d 7.86 (m, 4H), 7.72 (d, 2H J9 Hz), 7.08 (d, 2H, J9 Hz), 4.85 (m, 0.5H), 4.42 (m, 0.5H), 4.18 (m, 2H), 3.78 (m, 1H), 3.62 (m, 1H), 1.32 (s, 6H), 1.12 (m, 3H). 0886 MS (DCI/NH3) m/e 468 (MNH4).

EXAMPLE 69

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-benzyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 69A

3-benzyl-1-(4-methoxybenzyl)-2,5-dioxo-4,4-dimethylimidazolidine 0887 The title compound was prepared as in Example 68B but using benzyl iodine (3.9 g, 18 mmol) in place of iodoethane. Purification on silica gel with 50% ethyl acetate provided 4.0 g of title compound. 0888 MS (DCI/NH3) m/e 356 (MNH4).

EXAMPLE 69B

3-benzyl-2,5-dioxo-4,4-dimethylimidazolidine 0889 A solution of 3-benzyl-1-(4-methoxybenzyl)-2,5-dioxo-4,4-dimethylimidazolidine (3.9 g, 11.54 mmol) in acetonitrile (100 mL) was treated with a solution of ammonium cerium nitrate (31 g, 57.7 mmol) in 65 mL of water, stirred at 25 C. for 15 minute, then diluted the reaction with ethyl acetate and partitioned between ethyl acetate and brine. The organic layer was dried, filtered, and concentrated. Purification by recrystalization with ethyl acetate/hexane provided 1.58 g (7.25 mmol, 63%) of title compound as white solid. 0890 MS (DCI/NH3) m/e 236 (MNH4).

EXAMPLE 69C

1-(4-cyano-1,1-biphenyl-4-y)oxy-3-(3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)-2-propanone 0891 The title compound was prepared as in Example 68D but using 3-benzyl-2,5-dioxo-4,4-dimethylimidazolidine (0.5 g, 2.28 mmol) in place of using 3-ethyl-2,5-dioxo-4,4-dimethylimidazolidine. Purification on silica gel with 30% ethyl acetate/cloroform provided 634 mg of title compound. 0892 MS (DCI/NH3) m/e 485 (MNH4).

EXAMPLE 69D

()-N-1-(4-cyano-1,1-biphenyl-4-yl)oxymethyl-2-(3-ethyl-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0893 Example 69C (0.62 g, 1.33 mmol) was processed sequentially according to the precedures in Example 2D, 2E, and 2F without purification of the intermediates. Purification on silica gel with 70% ethyl acetate/hexanes provided 230 mg (0.45 mmol) of the title compound. 0894 1H NMR (300 MHz, DMSO) 9.95 (s, 0.5H), 9.64 (s, 0.5H), 8.35 (s, 0.5H), 7.94 (s, 0.5H), d 7.86 (m, 4H), 7.75 (d, 2H, J9 Hz), 7.30 (d, 2H, J9 Hz), 7.25 (m, 3H), 7.06 (m, 2H), 4.90 (m, 0.5H), 4.52 (s, 2H), 4.50 (m, 0.5H), 4.18 (m, 2H), 3.82 (m, 1H), 3.62 (m, 1H), 1.22 (s, 6H); 0895 MS (DCI/NH3) m/e 530 (MNH4).

EXAMPLE 70

()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 70A

1-(4-cyano-1,1-biphenyl-4-y)oxy-3-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)-2-propanol 0896 A solution of 5,5-dimethylhydantoin (2.0 g, 15.6 mmol) in DMF (20 mL) was treated with sodium tert-butoxide (1.5 g, 15.6 mmol), stirred for 10 minute, treated with iodomethane (2.2 g, 15.6 mmol), stirred at 40 oC for 3 hours. The resulting solution was treated with sodium tert-butoxide (1.5 g, 15.6 mmol) followed by 3-(4-cyano-1,1-biphenyl-4-y)oxy-(1,2) oxirane (1.15 g, 4.58 mmol ), stirred at 100 C. for 20 minute, treated with HCl solution (10%) and partitioned between ethyl acetate and brine. The organic layer was dried and concentrated to provide 1.35 g (75%) of title compound as white solid. 0897 MS (DCI/NH3) m/e 411 (MNH4).

EXAMPLE 70B

1-(4-cyano-1,1-biphenyl-4-y)oxy-3-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)-2-propanone 0898 Example 70A (1.35 g g, 3.4 mmol) was processed according to the procedures in Example 2C. Purification on silica gel with 30% ethyl acetate provided 1.2 g (3.1 mmol, 90%) of the title compound. 0899 MS (DCI/NH3) m/e 409 (MNH4).

EXAMPLE 70C

()-N-1-(4-cyano-1,1-biphenyl-4-y)oxymethyl-2-(3,5,5-trimethyl-2,4-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0900 Example A-264890.0-B (1.2 g, 3.07 mmol) was processed sequentially according to the precedures in Example 2D, 2E, and 2F without purification of the intermediates. Purification on silica gel with 30% ethyl acetate/hexanes provided 380 mg (2.29 mmol) of the title compound. 0901 1H NMR (300 MHz, DMSO) 9.90 (s, 0.5H), 9.68 (s, 0.5H), 8.38 (s, 0.5H), 7.98 (s, 0.5H), d 7.88 (m, 4H), 7.72 (d, 2H, J9 Hz), 7.08 (d, 2H, J9 Hz), 4.92 (m, 0.5H), 4.42 (m, 0.5H), 4.20 (m, 2H), 3.50 (m, 2H), 2.88 (s, 3H), 1.32 (s, 6H); 0902 MS (DCI/NH3) m/e 454 (MNH4).

EXAMPLE 71

N-1-(4-methoxy1,1-biphenyl-4-yl)sulfonylmethylethyl-N-hydroxyformamide

EXAMPLE 71A

4-methoxy-4-thiomethyl Biphenyl 0903 A solution of 4-bromothioanisole (6.15 g, 29.4 mmol) in DMF (60 mL) was treated sequentially with palladium (II) acetate (0.34 g, 1.5 mmol) and tri-o-tolylphosphine (0.94 g, 3.0 mmol) then 4-methoxyphenylboronic acid (5.06 g, 32.3 mmol) and cesium carbonate (19.2 g, 58.8 mmol). The mixture was stirred at 75 C. for 8 hours, then rt for 15 hours. The resulting suspension was partitioned between water and ether/hexane, 2:1. The organic layer was dried with Mg2SO4, filtered, and concentrated to provide crude product as a yellow solid. Recrystallization in ether at -20 C. afforded 2.61 g (39%) of the title compound. 0904 MS (ESI) m/e 231 (MH).

EXAMPLE 71 B

4-(4-methoxyphenyl)-phenyl methyl sulfone 0905 A solution of Example 71A (2.61 g, 11.3 mmol) in chloroform (100 mL) was treated with m-chloroperbenzoic acid (6.52 g, 22.7 mmol), stirred at 0 C. for 3 hours and then warmed to 10 C. over 1 hour. The mixture was partitioned between dilute sodium bicarbonate aqueous solution and chloroform, dried (Mg2SO4), filtered, and concentrated to provide crude product as a white solid. Recrystallized in dichloromethane and ether to afford 1.89 g (64%) of the title compound. 0906 MS (ESI) m/e 263 (MH) and 280 (MNH4).

EXAMPLE 71C

N-1-(4-methoxyl1,1-biphenyl-4-yl)sulfonylmethylethyl-N-benzyloxy Amine 0907 A suspension of Example 71B (0.26 g, 1.0 mmol) in THF (40 mL) cooled to 78 C. under argon atmosphere was treated with n-BuLi (0.40 mL of a 2.5 M solution in hexane, 1.0 mmol) and stirred for 3 hours. The resulting suspension was treated with BF3.Et2O (0.127 mL, 1.0 mmol) then the O-Benzyloxime of acetaldehyde (0.15 g, 1.0 mmol) (Stewart, et. al. J. Med. Chem. 1997, vol. 40, number 13, pages 1955-1968) in THF (10 mL), and stirred 1 hour at 0908 78 C. and 1 hour at 25 C. The mixture was partitioned between ether and pH 7 phosphate buffer. The organic extracts were washed with brine, dried (Mg2SO4), filtered, and concentrated to afford crude product as a white powder which was purified on silica gel with dichloromethane/methanol to provide 0.15 g (36%) of the title compound. 0909 MS (ESI) m/e 412 (MH).

EXAMPLE 71D

N-1-(4-methoxyl1,1-biphenyl-4-yl)sulfonylmethylethyl-N-nenzyloxyformamide 0910 A solution of Example 71c (0.11 g, 0.27 mmol) in THF (50 mL) cooled to 0 C. under argon atmosphere was treated with formic acetic anhydride (0.24 g, 2.7 mmol), stirred for 5 minutes at 0 C. then rt for 16 hours. Partitioned between 1 N Hcl and ethyl acetate. Washed organic extracts with brine, dried (Mg2SO4), filtered, and concentrated to provide crude oil product which was purified on silica gel with dichloromethane/methanol to afford 114 mg (96%) of the title compound. 0911 MS (ESI) m/e 440 (MH) and 457 (MNH4).

EXAMPLE 71E

N-1-(4-methoxy1,1-biphenyl-4-yl)sulfonylmethylethyl-N-hydroxyformamide 0912 A solution of Example 71D (114 mg, 0.26 mmol) in THF (20 mL) was treated with 10% palladium on carbon (35 mg, catalytic amount) and hydrogen gas at atmospheric pressure and stirred at rt for 18 hours. Filtered the suspension through Celite pad and concentrated to provide crude product as a white solid which was purified by trituration in ethyl acetate to afford 66 mg (73%) of the title compound. 0913 mp 197-198 C.; 0914 1H NMR (DMSO-d6) 1.16 (d, 1.5H, J6.6 Hz), 1.22 (d, 1.5H, J6.6 Hz), 3.43-3.70 (m, 2H), 3.82 (s, 3H), 4.28-4.41 (m, 0.5H), 4.62-4.76 (m, 0.5H), 7.08 (d, 2H, J8.7 Hz), 7.74 (d, 2H, J8.7 Hz), 7.87-7.96 (m, 4.5H), 8.08 (s, 0.5H), 9.47 (s, 0.5H), 9.89 (s, 0.5H); 0915 MS (ESI) m/e 350 (MH), 367 (MNH4); 0916 Anal. Calcd for: C17H19NO5S.H2OC, 55.57; H, 5.76; N, 3.81. Found: C, 55.32; H, 5.20; N, 3.67.

EXAMPLE 72

N-1-(4-chloro1,1-biphenyl-4-yl)sulfonylmethylethyl-N-hydroxyformamide 0917 The title compound was synthesized according to the procedures described in Example 71 except using 4-chlorophenylboronic acid in place of 4-methoxyphenylboronic acid in Example 71A. Purification of the crude final product by recrystallization in ethyl acetate afforded 36 mg of title compound. 0918 mp 178-180 C.; 0919 1H NMR (DMSO-d6) 1.16 (d, 1.5H, J6.6 Hz), 1.22 (d, 1.5H, J6.6 Hz), 3.50 (dd, 1H, J4.8,14.7 Hz), 3.57-3.73 (m, 1H), 4.28-4.41 (m, 0.5H), 4.61-4.77 (m, 0.5H), 7.59 (d, 2H, J8.4 Hz), 7.81 (d, 2H, J8.4 Hz), 7.91 (s, 0.5H), 7.92-8.00 (m, 4H), 8.07 (s, 0.5H), 9.45 (s, 0.5H), 9.86 (s, 0.5H); 0920 MS (ESI) m/e 354 (MH), 376 (MNa); 0921 Anal. Calcd for: C16H16NO4SCl C, 54.31; H, 4.55; N, 3.95. Found: C, 54.46; H, 4.43; N, 3.85.

EXAMPLE 73

N-1-4-(1,3-benzodioxol-5-yl)phenylsulfonylmethylethyl-N-hydroxyformamide 0922 The title compound was synthesized according to the procedures described in Example 71 except using 3,4-methylenedioxybenzeneboronic acid in place of 4-methoxyphenylboronic acid in Example 71A. mp 200-201 C.; 0923 1H NMR (DMSO-d6) 1.16 (d, 1.5H, J6.6 Hz), 1.22 (d, 1.5H, J6.6 Hz), 3.44-3.70 (m, 2H), 4.28-4.40 (m, 0.5H), 4.61-4.76 (m, 0.5H), 6.11 (s, 2H), 7.06 (d, 1H, J7.8 Hz), 7.29 (d, 1H, J8.4 Hz), 7.39 (s, 1H), 7.86-7.94 (m, 4.5H), 8.08 (s, 0.5H), 9.48 (s, 0.5H), 9.90 (s, 0.5H); 0924 MS (ESI) 364 (MH), 381 (MNH4); 0925 Anal. Calcd for: C17H17NO6S C, 56.19; H, 4.71; N, 3.85. Found: C, 55.97; H, 4.62; N, 3.81.

EXAMPLE 74

N-1-4-(4-chlorophenoxy)phenylsulfonylmethylethyl-N-hydroxyformamide

EXAMPLE 74A

4-chlorophenoxyphenyl methyl Sulfone 0926 A solution of 4-chlorophenol (5.54 g, 43 mmol) in DMSO (75 mL) was treated sequentially with potassium t-butoxide (5.15 g, 46 mmol) then with a solution of 4-fluorophenyl methyl sulfone (5.00 g, 29 mmol) in DMSO (25 mL), heated at 120 C. for 2 hours, cooled to rt, then partitioned between dichloromethane and 1 N sodium hydroxide, dried (Mg2SO4), filtered, and concentrated to give crude product as a white solid. Recrystallization from ethyl acetate and hexane afforded 5.44 g (66%) of the title compound. 0927 MS (ESI) m/e 300 (MNH4).

EXAMPLE 74B

N--4-(4-chlorophenoxy)phenylsulfonylmethylethyl-N-hydroxyformamide 0928 The title compound was prepared from Example 74A according to the procedures described in Example 71C-71E. Purification of the crude final compound by recrystallization in ethyl acetate afforded 388 mg of the title compound. 0929 mp 144-145 C.; 0930 1H NMR (DMSO-d6) 1.15 (d, 1.5H, J6.6 Hz), 1.21 (d, 1.5H, J6.6 Hz), 3.39-3.68 (m, 2H), 4.25-4.37 (m, 0.5H), 4.60-4.70 (m, 0.5H), 7.16-7.23 (m, 4H), 7.53 (d, 2H, J8.9 Hz), 7.83-7.92 (m, 2.5H), 8.06 (s, 0.5H), 9.45 (s, 0.5H), 9.87 (s, 0.5H); 0931 MS (ESI) 370 (MH), 387 (MNH4); 0932 Anal. Calcd for: C16H16NO5SCl C, 51.96; H, 4.36; N, 3.78. Found: C, 52.22; H, 4.37; N, 3.80.

EXAMPLE 75

N-1-(4-methoxyl1,1-biphenyl-4-yl)sulfonylmethylpropyl-N-hydroxyformamide 0933 Example 75A 0934 1-(4-methoxy 1,1-biphenyl-4-yl)sulfonyl-2-butanol 0935 A solution of Example 71B (0.70 g, 2.67 mmol) in THF (200 mL) cooled to 78 C. under argon was treated with n-BuLi (1. 17 mL of 2.5 M solution in hexane, 2.93 mmol), stirred 4 hours at 78 C., then treated with propionaldehyde (0.40 mL, 5.34 mmol) dropwise. Allowed reaction mixture to warm to rt over 1.5 hour, quenched with saturated aqueous NH4Cl solution (50 mL), partitioned between ether and water, dried (Mg2SO4), filtered, and concentrated to afford 0.90 g of crude product which was purified on silica gel with dichloromethane/methanol to provide 0.78 g (91%) of the title compound. 0936 MS (ESI) m/e 321 (MH), 338 (MNH4).

EXAMPLE 75B

1-(4-methoxy1,1-biphenyl-4-yl)sulfonyl-1-butene 0937 A solution of Example 75A (0.45 g, 1.40 mmol) in dichloromethane (40 mL) cooled to 0 C. was treated sequentially with triethylamine (0.29 mL, 2.11 mmol) and methanesulfonyl chloride (0.12 mL, 1.55 mmol) dropwise. Stirred at rt for 3 hours then treated with 1,8-diazabicyclo5.4.0undec-7-ene (0.21 mL, 1.40 mmol), refluxed for 2 hours, cooled to rt, and partitioned between dilute sodium bicarbonate solution and dichloromethane. The organic extract was washed with 1 N Hcl, then brine, dried (Mg2SO4), filtered, and concentrated to afford white solid crude product. Recrystallization in ether at 20 C. provided 0.34 g (80%) of title compound. 0938 MS (ESI) ni/e 303 (MH), 320 (MNH4).

EXAMPLE 75C

N-1-(4-methoxy1,1-biphenyl-4-yl)sulfonylmethylpropyl-N-hydroxy Amine 0939 A solution of Example 75B (0.34 g, 1.12 mmol) in THF (40 mL) was treated with hydroxylamine hydrochloride (0.39 g, 5.62 mmol) and potassium carbonate (0.78 g, 5.62 mmol), refluxed for 5 hours, cooled to rt, partitioned between ether and water, dried (Mg2SO4), and concentrated to give crude product as a clear, colorless oil. Recrystallization from ethyl acetate and ether provided 0.25 g (67%) of the title compound. 0940 MS (ESI) m/e 336 (MH).

EXAMPLE 75D

N-1-(4-methoxy1,1-biphenyl-4-yl)sulfonylmethylpropyl-N-hydroxyfornamide 0941 A solution of Example 75C (0.24 g, 0.72 mmol) in THF (30 mL) cooled to 0 C. was treated with formic acetic anhydride (64 mg, 0.72 mmol), stirred for 2 hours, partitioned between water and dichloromethane, dried (Mg2SO4), filtered, and concentrated to afford 0.25 g of crude product which was recrystallized in ethyl acetate to provide 106 mg (41%) of the title compound. 0942 mp 199-200 C.; 0943 1H NMR (DMSO-d6) 0.69-0.80 (m, 3H), 1.40-1.69 (m, 2H), 3.41-3.69 (m, 2H), 3.82 (s, 3H), 3.96-4.07 (m, 0.5H), 4.43-4.54 (m, 0.5H), 7.08 (d, 2H, J9.0 Hz), 7.71-7.78 (m, 2H), 7.87-7.96 (m, 4.5H), 8.17 (s, 0.5H), 9.49 (s, 0.5H), 9.84 (s, 0.5H); 0944 MS (ESI) 364 (MH), 381 (MNH4); 0945 Anal. Calcd for: C18H21NO5S C, 59.48; H, 5.82; N, 3.85. Found: C, 59.67; H, 5.77; N, 3.80.

EXAMPLE 76

N-1-1,1-dimethyl-2-(4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide

EXAMPLE 76A

4-(4-trifluoromethylphenyl)-phenyl Methyl Sulfone 0946 The title compound was prepared according to the procedure given in Example 73A substituting 4-trifluoromethylphenylboronic acid for 3,4-methylenedioxybenzeneboronic acid. Purification by recrystallization in ethyl acetate and ether afforded 3.70 g (72%) of the title compound. 0947 MS (ESI) m/e 318 (MNH4).

EXAMPLE 76B

1-(4-trifluoromethyl1,1-biphenyl-4-yl)sulfonyl-2-methyl-2-propanol 0948 The title compound was prepared according to the procedure described in Example 75A substituting Example 76A for Example 71B and substituting acetone for propionaldehyde. Purification of crude product by recrystallization in ethyl acetate, ether, and pentane provided 1.40 g (73%) of the title compound. 0949 MS (ESI) m/e 376 (MNH4).

EXAMPLE 76C

N-1-1,1-dimethyl-2-(4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 0950 The title compound was prepared from Example 76B according to the procedures described in Examples 75B, 75C and 75D. Purification of the final product by recrystallization in ethyl acetate and ether provided 17 mg of the title compound. 0951 mp 167-169 C.; 0952 1H NMR (DMSO-d6) 1.52 (s, 6H), 3.71 (s, 2H), 7.83-8.03 (m, 8.5H), 8.17 (s, 0.5H), 9.43 (s, 0.5H), 10.0 (s, 0.5H); 0953 MS (ESI) 402 (MH), 419 (MNH4), 424 (MNa); 0954 Anal. Calcd for: C18H18NO4F3SC, 53.86; H, 4.52; N, 3.48. Found: C, 53.58; H, 4.48; N, 3.19.

EXAMPLE 77

N-1-(phenylmethoxy)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 0955 The title compound was synthesized according to the procedures described in Examples 75A-75D except substituting Example 76A for Example 71B and substituting benzyloxyacetaldehyde for propionaldehyde in Example 75A. Purification of the crude final product by recrystallization in ethyl acetate afforded 0.53 g of title compound. 0956 mp 172 C.; 0957 1H NMR (DMSO-d6) 3.37-3.61 (m, 3H), 3.61-3.72 (m, 1H), 4.28-4.50 (m, 2.5H), 4.81-4.93 (m, 0.5H), 7.20-7.35 (m, 5H), 7.85-8.06 (m, 8.5H), 8.18 (s, 0.5H), 9.57 (s, 0.5H), 9.96 (s, 0.5H); 0958 MS (ESI) 494 (MH), 511 (MNH4); 0959 Anal. Calcd for: C24H22NO5F3S C, 58.41; H, 4.49; N, 2.83. Found: C, 58.43; H, 4.54; N, 2.77.

EXAMPLE 78

N-1-(hydroxymethyl)-2-1(4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 0960 A solution of Example 78 (35 mg, 0.07 mmol) in THF (3 mL) and methanol (5 mL) was treated with palladium on carbon, 10% (30 mg, 0.03 mmol) and hydrogen gas at atmospheric pressure, stirred at rt for 16 hours, filtered through Celite, and concentrated to afford crude product. Purification by recrystallizations in ethyl acetate, ether, and hexane provided 20 mg (70%) of the title compound. 0961 mp 159-161 C.; 0962 1H NMR (DMSO-d6) 3.25-3.68 (m, 4H), 3.98-4.10 (m, 0.5H), 4.54-4.66 (m, 0.5H), 4.97-5.09 (m, 1H), 7.81-8.07 (m, 8.5H), 8.14 (s, 0.5H), 9.44 (s, 0.5H), 9.85 (s, 0.5H); 0963 MS (ESI) 404 (MH), 421 (MNH4), 426 (MNa); 0964 Anal. Calcd for: C17H16NO5F3S C, 50.61; H, 3.99; N, 3.47. Found: C, 50.57; H, 3.93; N, 3.37.

EXAMPLE 79

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylthiolethyl-N-hydroxyformamide

EXAMPLE 79A

1-(4-trifluoromethyl1,1-biphenyl-4-yl)thiol-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-2-propanone 0965 The mixture of example 46A (698 mg, 1.88 mmol), tetrakis(triphenyphosphine) palladium(0) (217 mg, 0.19 mmol), 4-triflorophenylboronic acid (714 mg, 3.76 mmol) and NaOH (IM, 3.76 mL, 3.76 mmol) in DME (20 mL) was refluxed under argon for 4 hour. The mixture was evaporated to a small volume, and partitioned between CH2Cl2/brine. The CH2Cl2 layer was collected, dried (Na2SO2), filtered and evaporated to dryness. Purification of the crude final product on silica gel with 20%-40% ethyl acetate/CH2Cl2 provided 0.820 g of the title compound. MS (DCI/NH3) m/e 454 (MNH4), 437 (MH).

EXAMPLE 79B

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylthiolethyl-N-hydroxyformamide 0966 The title compound was obtained following the procedures in Examples 2D-F (inclusive) but substituting Example 79A (0.82 g, 1.88 mmol) for Example 2C. Purification of the crude final product on silica gel with 5% methanol/dichloromethane provided 434 mg of the title compound. 0967 mp 172-174 C.; 0968 1H NMR (300 MHz, d6-DMSO) 9.75 and 9.52 (br s, 1H), 8.37 and 8.33 (s, 1H), 8.31 and 7.77 (s, 1H), 7.90 (d, 2H, J8.4 Hz), 7.81 (d, 2H, J8.4 Hz), 7.71 (m, 2H), 7.47 (m 2H), 4.60 and 4.09 (m, 1H), 3.52-3.77 (m, 2H), 3.08-3.46 (m, 2H), 1.28 and 1.25 and 1.23 (s, 6H); 0969 MS (DCI/NH3) m/e499 (MNH4), 482 (MH); 0970 Anal. calcd for C22H22F3N3O4S.0.5 CH3OH: C, 54.31; H, 4.86; N, 8.44. Found: C, 54.43; H, 4.82; N, 8.08.

EXAMPLE 80

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 0971 Example 79 was converted to example 80 following the procedure described in example 46D. 0972 mp 180-182 C.; 0973 1H NMR (300 MHz, d6-DMSO) d 9.66 and 9.51 (br s, 1H), 8.39 and 8.35 (s, 1H), 8.10 and 7.73 (s, 1H), 7.79-8.02 (m, 6H), 7.89 (d, 2H, J8.4 Hz), 4.91 and 4.55 (m, 1H), 3.45-3.80 (m, 4H), 1.24 and 1.23 and 1.21 (s, 6H). 0974 MS (DCI/NH3) m/e531 (MNH4), 514 (MH); 0975 Anal. calcd for C22H22F3N3O6S.0.75 H2O: C, 50.14; H, 4.49; N, 7.97. Found: C, 50.27; H, 4.49; N, 7.97.

EXAMPLE 81

N-1-(2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide

EXAMPLE 81A

1-bromo-3-(2,5-dioxoimidazolidin-1-yl)propan-2-one 0976 The title compound was prepared following the procedures in examples 16A and 16B, but substituting hydantoin for 1,5,5-trimethylhydantoin.

EXAMPLE 81B

N-1-(2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1 -biphenyl-4-yloxyethyl-N-hydroxyformamide 0977 The title compound was prepared following the sequence described in described in examples 16C and 16E, but substituting 81 A for 16B and 4-(4-trifluoromethoxy-phenyl)phenol for 4-bromophenol. 0978 1H NMR (DMSO-66) 9.92 (s, 0.5H), 9.60 (bs, 0.5H), 8.31 (s, 0.5H), 8.16 (s, 0.5H), 8.14 (s, 0.5H), 7.92 (s, 0.5H), 7.76-7.72 (m, 4H), 7.64-7.62 (d, 4H, J8.4 Hz), 7.42-7.40 (d, 4H, J8.6 Hz), 7.02-6.98 (m, 4H), 4.84-4.82 (m, 0.5H), 4.38-4.35 (m, 0.5H), 4.19-4.04 (4H); 0979 Anal. Calcd for: C20H18N3O6F3: C, 52.98; H, 4.00; N, 9.13. Found: C, 53.01; H, 4.03; N, 9.13.

EXAMPLE 82

N-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0980 The title compound was prepared following the procedures described in example 46A, 46B, 46C and 46D, except substituting example 16B for 23A in example 46A and 4-trifluoromethylbenzeneboronic acid for 4-butyloxybenzeneboronic acid in example 46B. 0981 1H NMR (d6-DMSO) 9.70 (s, 0.5H), 9.54 (s, 0.5H), 8.10 (s, 0.5H), 8.05-7.97 (m, 6H), 7.89 (d, 2H, J7.8 Hz), 7.75 (s, 0.5H), 4.97-4.86 (m, 0.5H), 4.60-4.48 (m, 0.5H), 3.80-.344 (m, 4H), 2.75 (s, 3H), 1.24 (s, 3H), 1.22 (s, 3H); 0982 MS (ESI) 528 (MH), 545 (MNH4), 526 (MH); 0983 Anal. Calcd for: C23H24N3O6SF3 C, 52.36; H, 4.58; N, 7.96. Found: C, 52.05; H, 4.70; N, 7.63.

EXAMPLE 83

N-1-(4-butyl1,1-biphenyl-4-yl)oxymethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0984 The title compound was prepared following the procedures described in example 16C and 16E, except substituting example 26A for 16B and 4-(4-butylphenyl)phenol for 4-bromophenol. 0985 1H NMR (d6-DMSO) 10.00-9.94 (br, 0.5H), 9.64-9.58 (br, 0.5H), 8.34 (s, 0.5H), 7.98 (s, 0.5H), 7.58 (d, 2H, J8.8 Hz), 7.52 (d, 2H, J8.6 Hz), 7.24 (d, 2H, J8.5 Hz), 7.00-6.92 (m, 2H), 4.92-4.79 (m, 0.5H), 4.41-4.30 (m, 0.5H), 4.20-4.03 (m, 2H), 3.95 (d, 2H, J7.8 Hz), 3.75-3.57 (m, 2H), 2.86 (s, 1.5H), 2.85 (s, 1.5H), 2.60 (t, 2H, J7.4 Hz), 1.63-1.51 (m, 2H), 1.39-1.25 (m, 2H), 0.91 (t, 3H, J7.4 Hz); 0986 MS (ESI) 440 (MH), 457 (MNH4), 438 (MH); 0987 Anal. Calcd for: C24H29N3O5.0.25 H2OC, 64.92; H, 6.69; N, 9.46. Found: C, 64.76; H, 6.62; N, 9.29.

EXAMPLE 84 0988 N-1-(3-methy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 0989 The title compound was prepared following the procedures described in example 16C and 16E, except substituting example 26A for 16B and 4-(4-trifluoromethoxy)phenol for 4-bromophenol. 0990 1H NMR (d6-DMSO) 10.02-9.92 (br, 0.5H), 9.64-9.58 (br, 0.5H), 8.35 (s, 0.5H), 7.98 (s, 0.5H), 7.74 (d, 2H, J8.9 Hz), 7.64 (d, 2H, J8.8 Hz), 7.41 (d, 2H, J8.1 Hz), 7.03-6.97 (m, 2H), 4.91-4.82 (m, 0.5H), 4.41-4.31 (m, 0.5H), 4.21-4.07 (m, 2H), 3.96 (d, 2H, J7.7 Hz), 3.72-3.57 (m, 2H), 2.86 (s, 1.5H), 2.85 (s, 1.5H); 0991 MS (ESI) 468 (MH), 485 (MNH4), 466 (MH); 0992 Anal. Calcd for: C21H20N3O6F3 C, 53.96; H, 4.31; N, 8.99. Found: C, 53.85; H, 4.40; N, 8.85.

EXAMPLE 85

N-4-4-(4-chloro1,1-biphenyl-4-yl)sulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide

EXAMPLE 85A

N-4-4-(4-chloro1,1-biphenyl-4-yl)sulfonylmethyltetrahydro-2H-pyran-4-yl-N-benzyloxy Amine 0993 The title compound was prepared following the procedure described in example 54A, except using 4-chloro-40methylsulfone-biphenyl in place of phenoxyphenyl-4-chloro-4-methylsulfone.

EXAMPLE 85B

N-4-4-(4-chloro1,1-biphenyl-4-yl)sulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxy Amine 0994 A solution of 85A (0.436 g, 0.92 mmol) was treated with (CF3CO2)3B (4.6 mL, 1M solution in THF, 4.6 mmol), then stirred overnight at room temperature. The solution was concentrated, partitioned between ethyl acetate and aq. Na2CO3 and the organic layer was dried (Mg2SO4), filtered, concentrated and purified via column chromatography to give the title compound in 51% yield.

EXAMPLE 85C

N-4-4-(4-chloro1,1-biphenyl-4-yl)sulfonylmethyltetrahydro-2H-pyran-4-yl-N-hydroxyformamide 0995 Example 85B was converted to the title compound using the formylation procedure of example 2F. 0996 1H NMR (d6-DMSO) 9.52-9.48 (br, 1H), 8.23 (s, 1H), 7.97 (s, 4H), 7.81 (d, 2H, J8.4 Hz), 7.59 (d, 2H, J8.5 Hz), 3.72 (s, 2H), 3.69-3.46 (m, 4H), 2.35-1.94 (m, 4H); 0997 MS (ESI) 410 (MH), 427 (MNH4), 432 (MNa), 408 (MH).

EXAMPLE 86

N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 0998 The title compound was prepared following the procedures described in examples 46A, 46C and 46D, except using 4-(4-chlorophenoxy)thiophenolinstead of 4-bromothiophenol. 0999 1H NMR (d6-DMSO) 9.67 (s, 0.5H), 9.50 (s, 0.5H), 8.36 (d, 1H, J13.2 Hz), 8.10 (s, 0.5H), 7.90 (dd, 2H, J8.8, 3.0 Hz), 7.68 (s, 0.5H), 7.53 (d, 2H, J8.8 Hz), 7.20 (d, 4H, J8.8 Hz), 4.89-4.77 (m, 0.5H), 4.52-4.40 (m, 0.5H), 3.68-3.38 (m, 4H), 1.25-1.21 (m, 6H); 1000 MS (ESI) 496 (MH), 513 (MNH4), 494 (MH); 1001 Anal. Calcd for: C21H22N3O7SCl C, 50.85; H, 4.47; N, 8.47. Found: C, 50.53; H, 4.58; N, 8.25.

EXAMPLE 87

N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1002 The title compound was prepared following the procedures described in examples 46A, 46C and 46D, except using 16B in place of 23A and 4-(4-chlorophenoxy)thiophenol instead of 4-bromothiophenol. 1003 1H NMR (d6-DMSO) 9.78-9.71 (m, 0.5H), 9.58-9.49 (m, 0.5H), 8.09 (s, 0.5H), 7.89 (dd, 2H, J5.8, 2.9 Hz), 7.68 (s, 0.5H), 7.53 (d, 2H, J9.2 Hz), 7.20 (d, 4H, J8.8 Hz), 4.88-4.78 (m, 0.5H), 4.50-4.38 (m, 0.5H), 3.72-3.40 (m, 4H), 2.76 (s, 1.5H), 2.76 (s, 1.5H), 1.26-1.22 (m, 6H); 1004 MS (ESI) 510 (MH), 527 (MNH4), 508 (MH); 1005 Anal. Calcd for: C22H24N3O7SCl C, 51.81; H, 4.74; N, 8.23. Found: C, 51.61; H, 4.90; N, 7.96.

EXAMPLE 88

N-1-(4-butyl1,1-biphenyl-4-yl)sulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1006 The title compound was prepared following the procedures described in example 46A, 46B, 46C and 46D, except substituting example 16B for 23A in example 46A and 4-nbutylbenzeneboronic acid for 4-butyloxybenzeneboronic acid in example 46B. 1007 1HNMR(d6-DMSO) 9.70 (s, 0.5H), 9.54 (s, 0.5H), 8.10 (s, 0.5H), 7.94 (d, 4H, J1.0 Hz), 7.73 (s, 0.5H), 7.69 (dd, 2H, J8.1, 2.0 Hz), 7.35 (d, 2H, J8.4 Hz), 4.96-4.86 (m, 0.5H), 4.60-4.48 (m, 0.5H), 3.77-3.42 (m, 4H), 2.75 (s, 3H), 2.64 (t, 2H, J7.4 Hz), 1.64-1.54 (m, 2H), 1.40-1.27 (m, 2H), 1.24 (s, 3H), 1.22 (s, 3H), 0.91 (t, 3H, J7.5 Hz); 1008 MS (ESI) 516 (MH), 533 (MNH4), 538 (MCl), 514 (MH); 1009 Anal. Calcd for: C26H33N3O6S C, 60.56; H, 6.45; N, 8.14. Found: C, 60.32; H, 6.44; N, 8.09.

EXAMPLE 89

N-1-(4-butyl1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1010 The title compound was prepared according to the procedures of example 23B, except substituting4-(4-butylphenyl)-phenol in place of 4-(4-ethoxyphenyl)-phenol. 1011 1H NMR (DMSO-66) 0.93 (t, 3H, J8 Hz), 1.28 (s, 6H), 1.30-1.39 (m, 2H), 1.50-1.65 (m, 2H), 2.60 (t, 2H, J7 Hz), 3.51-3.64 (m, 1H), 3.67-3.80 (m, 1H), 4.03-4.24 (m, 2H), 4.35-4.48 (m, 0.5H), 4.78-4.92 (m, 0.5H), 6.99 (dd, 2H, J3,9 Hz), 7.25 (d, 2H, J9 Hz), 7.53 (d, 2H, J9 Hz), 7.58 (d, 2H, J9 Hz), 7.94 (s, 0.5H), 8.34 (d, 1H, J6 Hz), 8.39 (s, 0.5H), 9.55 (s, 0.5H), 9.87 (s, 0.5H); 1012 MS (ESI) 452 (MH); 1013 Anal. Calcd for: C25H31N3O5 C, 66.20; H, 6.88; N, 9.26. Found: C, 65.99; H, 6.71; N, 9.19.

EXAMPLE 90

N-1-3-(cyanomethyl)1,1-biphenyl-4-yloxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1014 The title compound was prepared according to the procedures of example 23B, except substituting 4-(3-cyanomethylphenyl)-phenol in place of 4-(4-ethoxyphenyl)phenol. 1015 1H NMR (DMSO-66) 2.80 (s, 6H), 3.52-3.83 (m, 2H), 4.10 (s, 2H), 4.12-4.25 (m, 2H), 4.38 (4.46, m-H, J0.5 Hz), 4.80-4.90 (m, 0.5H), 7.03 (dd, 2H, J3,9 Hz), 7.30 (d, 1H, J10 Hz), 7.48 (t, 1H, J10 Hz), 7.57-7.66 (m, 4H), 7.93 (s, 0.5H), 8.34 (d, 1H, J6 Hz), 8.39 (s, 0.5H), 9.55 (s, 0.5H), 9.88 (s, 0.5H); 1016 MS (ESI) 435 (MH); 1017 Anal. Calcd for: C23H24N4O5.0.25CH3CO2C2H5 C, 62.87; H, 5.71; N, 12.21. Found: C, 62.85; H, 5.80; N, 12.16.

EXAMPLE 91

N-1-4-(2-thienyl)phenoxymethyl-2-1-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1018 The title compound was preapred following the procedures of examples 16C and 16E, except substituting 4-(4-(2-thienyl)phenyl)phenol for 4-bromophenol in example 16C. 1019 1H NMR (DMSO-6) 1.29 (s, 6H), 2.80 (s, 3H), 3.54-3.66 (m, 1H), 3.69-3.84 (m, 1H), 4.04-4.22 (m, 2H), 4.33-4.47 (m, 0.5H), 4.77-4.90 (m, 0.5H), 6.96 (dd, 2H, J3,9 Hz), 7.08-7.13 (m, 1H), 7.38 (d, 1H, J3 Hz), 7.46 (d, 1H, J4 Hz), 7.59 (d, 2H, J9 Hz), 7.92 (s, 0.5H), 8.31 (s, 0.5H), 9.54 (s, 0.5H), 9.86 (s, 0.5H). MS (ESI) 416 (MH); 1020 Anal. Calcd for: C21H23N3O5S.0.25H2O C, 56.92; H, 5.61; N, 9.95. Found: C, 56.65; H, 5.48; N, 9.77.

EXAMPLE 92

N-1-(3-nitro 1,1-biphenyl-4-yl)oxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1021 The title compound was preapred following the procedures of examples 16C and 16E, except substituting 4-phenyl-2-nitrophenol for 4-bromophenol in example 16C. 1022 1H NMR (DMSO-6) 1.28 (s, 6H), 2.80 (s, 3H), 3.54-3.65 (m, 1H), 3.70-3.88 (m, 1H), 4.22-4.39 (m, 2H), 4.40-4.50 (m, 0.5H), 4.80-4.91 (m, 0.5H), 7.34-7.41 (m, 2H), 7.43-7.52 (m, 2H), 7.71 (d, 2H, J8 Hz), 7.87 (s, 0.5H), 8.0 (d, 1H, J9 Hz), 8.16 (dd, 1H, J3,6 Hz), 8.29 (s, 0.5H), 9.55 (s, 0.5H), 9.80 (s, 0.5H); 1023 MS (ESI) 455 (MH); 1024 Anal. Calcd for: C22H24N4O7 C, 57.88; H, 5.29; N, 12.27. Found: C, 57.62; H, 5.44; N, 11.95.

EXAMPLE 93

N-1-(4-methyl1,1-biphenyl-4-yl)oxymethyl-2-3-(methylsulfonyl)aminophenylethyl-N-hydroxyformamide

EXAMPLE 93A

3-(methylsulfonyl)amino-1-bromo-benzene 1025 The m-bromo aniline was dissolved in 40 mL of pyridine and cooled to 0 C. followed by addition of methansulfonyl chloride dropwise via syringe. After 10 min, the solution was warmed to room temperature and stirred for 4 h. Upon concentration in vacuo the residue was partitioned between 350 mL of H2O and 500 mL of CH2Cl2 in a separatory funnel. The organics were separated and washed with 100 mL of 3N HCl, 200 mL of sat'd NaHCO3 and dried over MgSO4. Upon filtration and concentration in vacuo an off-white solid was obtained. This product was recrystallized from CH2Cl2/Hexanes to afford 6.7 g (90%) of 93A as white needles.

EXAMPLE 93B

3-(methylsulfonyl)amino-1-(prop-2-enyl)-benzene 1026 Using a glass sealed vessel the sulphonamide 93A (3.0 g, 12.1 mmol) was suspended in 10 mL of toluene followed by addition of the allyltributyl tin reagent and bubbled with argon for 5 min. To the above suspension was added 280 mg (2 mol %) of Pd(PPh3)4 and the vessel sealed and heated at 120 C for 17h. After 15 min a homogeneous solution was obtained which turned dark brown after 30 min. After cooling, the catalyst was filtered off washing with CH2Cl2/MeOH. Concentration of the filtrate followed by purification on silica gel eluting with 10% Ethyl Acetate/Hexanes then 20% Ethyl Acetate/Hexanes afforded 93B, 0.99 g (38%) as a colorless oil which solidified upon standing.

EXAMPLE 93C

N-1-(4-methyl1,1-biphenyl-4-yl)oxymethyl-2-3-(methylsulfonyl)aminophenylethyl-N-hydroxyformamide 1027 The title compound was preapred from example 93B, first by epoxidizing as desribed in example 5C, then opening the epoxide with 4-hydroxy-4-biphenylcarbonitrile as in example 5F, then following the sequence of reactions described in examples 2C through 2F. 1028 1H NMR (DMSO-6) 2.32 (s, 3H), 2.88 (d, 2H, J6 Hz), 2.96 (s, 1H), 2.98 (s, 3H), 4.03-4.11 (m, 1H), 4.15-4.27 (m, 1,5H), 4.72-4.82 (bs, 0.5H), 6.97-7.10 (m, 4H), 7.05 (s, 1H), 7.20-7.30 (m, 3H), 7.50 (d, 2H, J9 Hz), 7.57 (d, 2H, J9 Hz), 7.73 (s, 0.5H), 8.25 (s, 0.5H), 9.18 (s, 0.5H), 10.01 (s, 0.5H); 1029 MS (ESI) 453 (MH); 1030 Anal. Calcd for: C24H26N2O5S C, 63.41; H, 5.76; N, 6.16. Found: C, 63.16; H, 6.12; N, 5.76.

EXAMPLE 94

N-1-3-(diethylamino)carbonylphenylmethyl-2-(4-methyl1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide

EXAMPLE 94A

3-bromo-1-(N,N-diethylcarboxamide)-benzene 1031 Diethylamine (10.0 ml, 97 mmol) was dissolved in 60 ml of dry ethyl ether and cooled to 0 C. Benzoyl chloride (3.67 ml, 28 mmol) was dissolved in 10 mL of dry ethyl ether and was slowly added dropwise via syringe to to the above solution. A white slurry developed upon addition and stirring was continued for 10 min at 0 C. then warmed to room temperature for 1 h. The mixture was poured into a separatory funnel containing 500 mL of ethyl ether and 75 mL of 10% NaOH. The organics were separated and washed a second time with 75 mL of 10% NaOH followed by 75 mL of 10% HCl then 200 mL of water. A final wash with 100 mL of brine followed by drying over MgSO4, filtering and then concentration in vacuo, afforded the 94A as a colorless liquid, 5.9 g (83%) which was used without further purification.

EXAMPLE 94B

N-1-3-(diethylamino)carbonylphenylmethyl-2-(4-methyl1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 1032 The title compound was prepared following the procedure described in examples 93B and 93C, except substituting 94A for 93A. 1033 1H NMR (DMSO-66) 0.98-1.20 (bd, 6H), 2.32 (s, 3H), 2.93 (d, 2H, J6 Hz), 3.11-3.48 (bd, 4H), 4.0-4.13 (m, 1H), 4.16-4.30 (m, 1.5H), 4.74-4.86 (bs, 0.5H), 6.98 (d, 2H, J9 Hz), 7.13-7.40 (m, 6H), 7.50 (d, 2H, J8 Hz), 7.56 (d, 2H, J9 Hz), 7.73 (s, 0.5H), 8.23 (s, 0.5H), 9.63 (s, 0.5H), 10.02 (s, 0.5H). MS (ESI) 461 (MH). Anal. Calcd for: C28H32N2O4.1.5H2O C, 68.97; H, 7.23; N, 5.74. Found: C, 68.96; H, 7.09; N, 5.42.

EXAMPLE 95

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(4-cyano1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 1034 The title compound was prepared using the procedures of examples 5F, 5G and 5H, except using example 3B in place of 5E. 1035 1H NMR (DMSO-6) 4.18-4.36 (m, 4H), 4.43-4.57 (bs, 0.5H), 4.97-5.03 (bs, 0.5H), 7.10 (d, 4H, J9 Hz), 7.77 (d, 4H, J9 Hz), 7.81-7.95 (m, 8H), 8.13 (s, 0.5H), 8.42 (s, 0.5H), 9.75 (s, 0.5H), 10.15 (s, 0.5H); 1036 MS (DCI/NH3) MH (490), M18 (507); 1037 Anal. Calcd for: C30H23N3O4.0.25H2O C, 72.93; H, 4.79; N, 8.50. Found: C, 72.80; H, 4.74; N, 8.26.

EXAMPLE 96

N-1-(4-cyano1,1-biphenyl-4-yl)oxymethyl-2-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1038 The title compound was prepared according to the procedures of example 23B, except substituting 4-(4-cyanophenyl)-phenol in place of 4-(4-ethoxyphenyl)-phenol. 1039 1H NMR (DMSO-6) 1.27 (s, 6H), 3.50-3.66 (m, 1H), 3.67-3.82 (m, 1H), 4.08-4.28 (m, 2H), 4.38-4.50 (m, 0.5H), 4.80-4.93 (m, 0.5H), 7.06 (dd, 2H, J3,9 Hz), 7.73 (d, 2H, J9 Hz), 7.82-7.93 (m, 4H), 7.94 (s, 0.5H), 8.35 (d, 1H, J6 Hz), 8.40 (s, 0.5H), 9.56 (s, 0.5H), 9.87 (s, 0.5H); 1040 MS (ESI) 421 (MH); 1041 Anal. Calcd for: C22H22N4O5.0.25H2O C, 61.89; H, 5.31; N, 13.12. Found: C, 61.82; H, 5.34; N, 12.82.

EXAMPLE 97

N-1-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(2-methoxyethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 1042 The title compound was prepared according to the procedures of example 23B, except substituting4-(4-(2-methoxyethoxy)-phenyl)-phenol in place of 4-(4-ethoxyphenyl)-phenol. 1043 1H NMR (DMSO-6) 1.26 (s, 6H), 3.33 (s, 3H), 3.50-3.64 (m, 1H), 3.66-3.69 (m, 2H), 3.70-3.81 (m, 1H), 4.03-4.22 (m, 4H), 4.35-4.48 (m, 0.5H), 4.78-4.90 (m, 0.5H), 6.98 (dd, 4H, J3,9 Hz), 7.55 (dd, 4H, J3,6 Hz), 7.91 (s, 0.5H), 8.33 (d, 1H, J7 Hz), 8.40 (s, 0.5H), 9.55 (s, 0.5H), 9.86 (s, 0.5H); 1044 MS (ESI) 470 (M1); 1045 Anal. Calcd for: C24H29N3O7 C, 61.13; H, 6.19; N, 8.91. Found: C, 60.86; H, 6.41; N, 8.65.

EXAMPLE 98

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-propoxy1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 1046 The title compound was prepared according to the procedures of example 23B, except substituting 4-(4-propyloxyphenyl)-phenol in place of 4-(4-ethoxyphenyl)-phenol. 1047 mp. 158-160 C. 1048 Mass Spec. (ESI): 456 (mH), 473 (m18), 454 (m-H), 490 (m35) 1049 1H NMR (DMSO-d6): 0.90 (3H, t, J6 Hz), 1.17 (2.4H, s), 1.20 (3.6H, s), 1.65 (2H, sextuplet, J6 Hz), 3.46-3.55 (1H, m), 3.59-3.74 (1H, m), 3.86 (2H, t, J6 Hz), 3.96-4.06 (1H, m), 4.06-4.14 (1H, m), 4.28-4.38 (0.6H, m), 4.72-4.81 (0.4H, m), 6.88 (4H, d, J4.8 Hz), 7.42, (2H, d, J4.8 Hz), 7.44 (2H, d, J4.8 Hz), 7.83 (0.4H, s), 8.24 (1H, s), 8.28 (0.6H, s), 9.43 (0.6H, s), 9.74 (0.4H, s); 1050 13C NMR (DMSO-d6): 10.4, 22.0, 24.4, 24.5, 36.0, 36.4, 52.1, 56.1, 57.8, 57.9, 64.7, 65.0,69.0, 114.8, 115.0, 127.2, 132.0, 132.8, 132.9, 155.0, 155.2, 157.0, 157.1, 157.9, 158.2, 163.1, 177.2, 177.3; 1051 Calc. for C24H29N306: C, 63.28; H, 6.42; N, 9.22. Found: C, 63.25; H, 6.48; N, 9.29.

EXAMPLE 99

N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-(4-pentyloxy1,1-biphenyl-4-yl)oxyethyl-N-hydroxyformamide 1052 The title compound was prepared according to the procedures of example 23B, except substituting4-(4-pentylyloxyphenyl)-phenol in place of 4-(4-ethoxyphenyl)-phenol. 1053 1H NMR (300 MHz, DMSO-6) 0.90 (t, 3H, J6.9 Hz), 1.27 (s, 6H), 1.3-1.5 (m, 4H), 1.7-1.8 (m, 2H), 3.5-3.8 (m, 2H), 3.98 (t, 2H, J6.9 Hz), 4.0-4.2 (m, 2H), 4.35-4.45 (m, 0.5H), 4.8-4.9 (m, 0.5H), 6.9-7.0 (m, 4H), 7.5-7.6 (m, 4H), 7.92 (s, 0.5H), 8.3-8.4 (m, 1.5H), 9.53 (s, 0.5H), 9.84 (s, 0.5H); 1054 MS (ESI) 484 (MH), 501 (MNH4); 1055 Anal. calcd for C26H33N3O6: C, 64.57; H, 6.87; N, 8.68. Found: C, 64.27; H, 6.85; N, 8.60.

EXAMPLE 100

N-1-3-(cyanomethyl)1,1-biphenyl-4-ylsulfonylmethyl-3-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 1056 The title compound was made according to the procedures of example 61, but using example 23A in place of example 16B and 4-thiol-3-cyanomethyl biphenyl in place of 4-thiol-4-biphenylcarbonitrile in example 61 A. 1057 1H NMR (300 MHz, d6-DMSO) 9.98 (br, 0.5H), 9.63 (br, 0.5H), 8.31 (s, 0.5H), 8.23 (s, 0.5H), 8.12 (s, 0.5H), 7.99-7.92 (m, 4H), 7.82 (s, 0.5H), 7.74 (m, 2H), 7.57 (t, 1H), 7.46 (d, 1H), 4.52 (m, 0.5H), 4.14 (s, 2H), 4.00 (m, 0.5H), 3.69-3.57 (m, 2H), 3 42-3.28 (m, 2H), 2.02-1.88 (m, 1H), 1.78-1.64 (m, 1H), 1.21 (s, 6H); 1058 MS (ESI) m/e 499 (MH); 1059 Anal. calcd for C24H26N4O6S: C, 57.82; H, 5.26; N, 11.24. Found: C, 57.56; H, 5.41; N, 10.89.

EXAMPLE 101

N-1-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1060 The title compound was prepared following the procedures of example 46, except substituting example 16B for 23A in example 46A and 4-trifluoromethoxybenzeneboronic acid for 4-butoxybenzeneboronic acid in example 46B. 1061 1H NMR (300 MHz, d6-DMSO) 9.72 (br, 0.5H), 9.56 (br, 0.5H), 8.10 (s, 0.5H), 7.99 (m, 4H), 7.94-7.88 (m, 2H), 7.74 (s, 0.5H), 7.53 (d, 2H), 4.91 (m, 0.5H), 4.54 (m, 0.5H), 3.75-3.44 (m, 4H), 2.75 (s, 3H), 1.24-1.22 (m, 6H); 1062 MS (ESI) m/e 544 (MH); 1063 Anal. calcd for C23H24F3N3O7S: C, 50.83; H, 4.45; N, 7.73. Found: C, 51.17; H, 4.77; N, 7.29.

EXAMPLE 102

N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(3-methy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1064 The title compound was made according to the procedures of example 61, but using example 26A in place of example 16B in example 61 A. 1065 1H NMR (300 MHz, d6-DMSO) 9.83 (s, 0.5H), 9.58 (s, 0.5H), 8.09 (s, 0.5H), 8.04-8.00 (m, 8H), 7.80 (s, 0.5H), 4.94-4.85 (m, 0.5H), 4.52-.4.43 (m, 0.5H), 3.91-3.88 (m, 2H), 3.78-3.44 (m, 4H), 2.80 (s, 1.5H), 2.79 (s, 1.5H); 1066 MS (ESI) m/e 457 (MH); 1067 Anal. calcd for C21H20N4O6S: C, 55.26; H, 4.42; N, 12.27. Found: C, 54.99; H, 4.38; N, 12.07.

EXAMPLE 103

N-1-3-(cyanomethyl)1,1-biphenyl-4-ylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1068 The title compound was prepared following the procedures of example 46, except substituting example 16B for 23A in example 46A and 3-cyanomethylbenzeneboronic acid for 4-butoxybenzeneboronic acid in example 46B. 1069 The title compound was made in the usual way from the -bromo ketone and 4-bromothiophenol. 1070 1H NMR (300 MHz, d6-DMSO) 9.71 (s, 0.5H), 9.56 (s, 0.5H), 8.10 (s, 0.5H), 8.03-7.94 (m, 4H), 7.75 (m, 2.5H), 7.57 (t, 2H), 7.46 (d, 2H), 4.96-4.88 (m, 0.5H), 4.59-4.49 (m, 0.5H), 4.14 (s, 2H), 3.69-3.48 (m, 4H), 2.75 (s, 3H), 1.24 (s, 3H), 1.22 (s, 3H); 1071 MS (ESI) m/e 499 (MH); 1072 Anal. calcd for C24H26N4O6S: C, 57.82; H, 5.26; N, 11.24. Found: C, 57.73; H, 5.36; N, 10.95.

EXAMPLE 104

N-1-(4-cyano1,1-biphenyl-4-yl)oxylmethyl-2-(1,6-dihydro-3-methyl-6-oxo-1-pyridazinyl)ethyl-N-hydroxyformamide 1073 The title compound was prepared following the procedures of example 3C and 3D, except substituting the potassium salt 6-methyl-3(2H)-pyridazinone (generated in situ with potassium carbonate) for potassium phthalimide in example 3C. 1074 1H NMR (300 MHz, CD3OD) 8.31 (s, 0.5H), 7.91 (s, 0.5H), 7.76 (s, 4H), 7.67.64 (d, i 5 2H), 7.38 (dd, 1H), 7.08 (d, 2H), 6.94 (dd, 1H), 5.20-5.11 (m, 0.5H), 4.64-4.52 (m, 2H), 4.42-4.32 (m, 2H), 4.27-4.19 (m 0.5H), 2.35 (s, 1.5H), 2.34 (s, 1.5H); 1075 MS (ESI) m/e 405 (MH); 1076 Anal. calcd for C22H20N4O4: C, 65.34; H, 4.98; N, 13.85. Found: C, 64.85 H, 5.36; N, 13.44.

EXAMPLE 105

()-N-1-(4-cyano1,1-biphenyl-4-yl)sulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide; 1077 The title compound was made according to the procedures of example 61, but using example 47A in place of example 16B in example 61A. 1078 1H NMR (300 MHz, d6-DMSO) 9.98 (s, 0.5H0, 9.62 (s, 0.5H), 8.31 (s, 0.5H), 8.22 (s, 0.5H), 8.12 (s, 0.5H), 8.05-7.96 (m, 8H), 7.82 (s, 0.5H), 4.55-4.46 (m, 0.5H), 4.07-3.97 (m, 0.5H), 3.70-3.56 (m, 2H), 3.32-3.24 (m, 2H), 2.02-1.88 (m, 0.5H), 1.76-1.64 (m, 0.5H), 1.21-1.18 (m, 6H); 1079 MS (ESI) m/e 485 (MH).

EXAMPLE 106

()-N-1-4-(4-fluorophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl -2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1080 The title compound was made according to the procedures of example 61, but using example 26A in place of example 16B and 4-(4-fluoroohenoxy)-benzene thiol in place of 4'thiol-4-biphenyl carbonitrile in example 61A. 1081 1H NMR (300 MHz, d6-DMSO) 9.66 (s, 0.5H), 9.50 (s, 0.5H), 8.39 (s, 0.5H), 8.35 (s, 0.5H), 8.10 (s, 0.5H), 7.88 (dd, 2H), 7.68 (s, 0.5H), 7.36-7.30 (m, 2H), 7.26-7.20 (m, 2H), 7.15 (d, 2H), 4.88-4.80 (m, 0.5H), 4.51-4.41 (m, 0.5H), 3.70-3.39 (m, 4H), 1.24-1.22 (m, 6H); 1082 MS (ESI) m/e 480 (MH); 1083 Anal. calcd for C21H22FN3O7S: C, 52.60; H, 4.62; N, 8.76. Found: C, 52.79; H, 4.57; N, 8.68.

EXAMPLE 107 1084 N-1-4-(4-pyridinyl)phenoxymethyl-2-(3,4,4-trimethy-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1085 The title compound was prepared following the procedures of examples 16C and 6E, except substituting4-(4-pyridinyl)-phenol in place of 4-bromophenol in example 16C. mp: 217-218 C. 1086 1H NMR (DMSO-d6): 9.53-9.97 (c, 1H), 8.55-8.60 (c, 2H), 8.32 (s, 1/2H), 7.92 (s, 1/2H), 7.77 (s, 1H), 7.75 (s, 1H), 7.65 (s, 1H), 7.64 (s, 1H), 7.01-7.08 (c, 2H), 4.82-4.89 (c, 1/2H), 4.39-4.46 (c, 1/2H), 4.18-4.25 (c, 1H), 4.08-4.17 (c, 1H), 3.71-3.83 (c, 1H), 3.57-3.66(c, 1H), 2.78(s, 1.5H), 2.77(s, 1.5H), 1.27(s, 3H), 1.26(s, 3H); 1087 MS (ESI()) 413 (MH), 435 (MNa), 847 (2MNa); 1088 Anal. Calcd for: C21H24N4O5.0.5H2O C, 59.84; H, 5.98; N, 13.29. Found: C, 60.18; H, 6.05; N, 13.10.

EXAMPLE 108

(S)-N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide

EXAMPLE 108A

(R)1-(4-(4-(trifluoromethoxyphenyl)phenoxy)-3-benzyloxy-2-propanol 1089 A solution of 4-(4-trifluoromethoxyphenyl)-phenol (1.854 g, 7.3 mmol) and (S)-2-(benzyloxymethyl)-oxirane (1.0 g, 6.1 mmol) in DMF (15 mL) was treated with potassium carbonate (1.007 g, 7.3 mmol), then stirred at 80 C. overnight. The reaction mixture was allowed to cool to 25 C., poured into water (100 mL) and extracted twice with ethyl acetate (200 mL2). The combined organics were washed with sat. aq. NH4Cl, water, brine, dried (Na2SO4), filtered, and concentrated. Purification via flash silica chromatography eluting with 20 to 25% ethyl acetate: hexane afforded 2.03 g (80% yield) of 108A as a white solid.

EXAMPLE 108B 1090 A solution of example 108A (1.505 g, 3.6 mmol), di-Boc hydroxylamine (1.007 g, 4.3 mmol), triphenyl phosphine (1.23 g, 4.7 mmol) in THF (15 mL) was treated with diethylazodicarboxylate (0.735 mL, 4.7 mmol) at room temperature, stirred for lh, then concentrated. The crude was purified by column chromatography eluting with 10% ethyl acetate: hexane to give 1.16 g (50%) of 108B.

EXAMPLE 108C 1091 A solution of example 108B (248 mg, 0.4 mmol) in THF (3mL) was hydrogenated (H2 balloon) overnight in the presence of 23 mg of 10%pd on carbon. The reaction mixture was filtered, concentrated and purified via silca gel column chromatography eluting with 25% ethyl acetate: hexane to afford 180 mg (85%)of the title compound.

EXAMPLE 108D 1092 A solution of example 108C (228 mg, 0.42 mmol), 5,5-dimethyl hydantoin (94 mg, 0.73 mmol) and triphenyl phospine (165 mg, 0.63 mmol) in THF (4 mL) was treated with diethylazodicarboxylate (0.1 mL, 0.63 mmol) added drowise via syringe. The resulting light yellow solution was stirred at 25 C. for 45 mn, concentarted and purigies via silca gel column chromatography eluting with 25% ethyl acetate: hexane to afford 193 mg (71%)of 108D.

EXAMPLE 108E

(S)-N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxy amine 1093 A solution of example 108D (191 mg, 0.29 mmol) in methylene chloride (3 mL) was treated with TFA (1.5 mL), added dropwise via syringe. The reaction was stirred at rt for 40 min then concentrated and the residue was partitioned between ethyl acetate and aq. NaHCO3. the organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated to afford 113 mg (86%) of 108E as a white solid.

EXAMPLE 108F

(S)-N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 1094 The title compound was prepared from 108E following the procedure of example 2F. 1095 MS (ESI) m/e 482 (MH).

EXAMPLE 109

(R)-N-1-(4,4-dimethy-2,5-dioxo-1-imidazolidinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 1096 The title compound was prepared following the procedures of example 108, except using (R)-2-(benzyloxymethyl)-oxirane in place of (S)-2-(benzyloxymethyl)-oxirane. 1097 1H NMR (300 MHz, d6-DMSO) 9.86 (s, 0.5H), 9.55 (s, 0.5H), 8.39 (s, 0.5H), 8.35 (s, 0.5H), 8.33 (s, 0.5H), 7.93 (s, 0.5H), 7.76-7.73 (m, 2H), 7.64 (d, 2H), 7.42 (d, 2H), 7.02 (dd, 2H), 4.91-4.80 (m, 0.5H), 4.47-4.38 (m, 0.5H), 4.23-4.06 (m, 2H), 3.79-3.50 (m, 2H), 1.27 (s, 1.5H), 1.26 (s, 1.5H); 1098 MS (ESI) m/e 482 (MH).

EXAMPLE 110

N-1-4-(trifluoromethoxy))1,1-biphenyl-4-yloxymethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 1099 The title compound was prepared according to the procedures of example 5, except avoiding the methylation step in example SB and substituting 4-(4-trifluoromethoxyphenyl)phenol for 4-hydroxy-4-biphenylcarbonitrile in example 5F . 1100 mp: 197.1-197.9 C.; 1101 1H NMR (300 MHz, DMSO-6) 1.27 (s, 6H), 1.70-2.00 (m, 2H), 3.35-3.46 (2H), 3.97-4.16 (m, 2.75H), 4.51 (br s, 0.25H), 7.00-7.03 (d, 2H, J9 Hz), 7.39-7.42 (d, 2H, J9 Hz), 7.60-7.63 (d, 2H, J9 Hz), 7.72-7.75 (d, 2H, J9 Hz), 8.25-8.35 (2H), 9.55 (s, 0.75H), 9.95 (br s, 0.25H); 1102 MS (ESI) m/e 496 (MH), 518 (mNa), 494 (mH), 530 (mCl); 1103 Anal. calcd for C23H24F3N3O6: C, 55.75; H, 4.88; N, 8.48. Found: C, 55.72; H, 5.07; N, 8.59.

EXAMPLE 111

N-1-4-(4-pyridinylthio)phenoxymethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1104 The title compound was prepared following the procedures of example 23B, except substituting (prepared by the addition of 4-hydroxythiophenol to 4-chloropyridine) for 4-(4-butyloxyphenyl)-phenol. 1105 1H NMR (300 MHz, DMSO-6) 1.258-1.272 (6H), 3.492-3.793 (m, 2H), 4.082-4.248 (m, 2H), 4.437 (m, 0.5H), 3.861 (m, 0.5H), 5.759 (s, 1H), 6.927-6.948 (dd, 2H, J1.5, 4.8 Hz), 7.063-7.102 (dd, 2H, J3, 8.7 Hz), 7.529-7.557 (d, 2H, J8.4 Hz), 7.939 (s, 0.5H), 8.323-8.343 (dd, 2H, J1.2, 4.8 Hz), 8.391 (s, 0.5H), 9.555 (s, 0.5H), 9.866 (s, 0.5H); 1106 MS (ESI) m/e 431 (MH), 453 (mNa), 429 (mH), 465 (mCl).

EXAMPLE 112

N-1-(4-chlorophenoxy)phenylsulfonylmethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 1107 The title compound was prepared according to the procedures of example 61, except substituting 4-(4-chlorophenoxy)benzene thiol for 4-thiol-4-biphenylcarbonitrile and example 47A for examplel6B in example 61A. 1108 1H NMR (d6-DMSO) 9.94 (s, 0.5H), 9.58 (s, 0.5H), 8.23 (d, 0.5H, J9.5 Hz), 8.11 (s, 0.5H), 8.05 (d, 0.5H, J9.2 Hz), 7.89-7.83 (m, 2H), 7.76 (s, 0.5H), 7.54-7.50 (m, 2H), 7.22-7.16 (m, 4H), 4.52-4.41 (m, 0.5H), 4.10-3.92 (m, 0.5H), 3.66-3.37 (m, 2H), 3.31-3.24 (m, 3H), 1.96-1.84 (m, 1H), 1.74-1.62 (m, 1H), 1.28-1.21 (m, 6H); 1109 MS (ESI) 508 (MH), 510 (MH), 532 (MNa).

EXAMPLE 113

N-1-(4-cyano1,1-biphenyl-4-yl)oxylmethyl-2-(1,6-dihydro-6-oxo-1-pyridazinyl)ethyl-N-hydroxyformamide 1110 The title compound was prepared following the procedures of example 104, except using pyridazinone in place of 6-methyl-3(2H)-pyridazinone. 1111 1H NMR (d6-DMSO) 9.99 (s, 0.5H), 9.64 (s, 0.5H), 8.28 (s, 0.5H), 7.96-7.83 (m, 5.5H), 7.75-7.71 (m, 2.OH), 7.47-7.41 (m, 1H), 7.07-6.95 (m, 3H), 5.11-5.00 (m, 0.5H), 4.62-4.12 (m, 4.5H); 1112 MS (ESI) 391 (MH), 413 (MNa), 389 (MH); 1113 Anal. Calcd for: C21H18N4O4.0.5H2O C, 63.15; H, 4.79; N, 14.02. Found: C, 63.33; H, 4.66; N, 13.68.

EXAMPLE 114

N-1-4-(aminosulfonyl)1,1-biphenyl-4-yloxymethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1114 The title compound was prepared following the procedures of examples 16C and 16E, except substituting 4-(4-sulfonamidephenyl)-phenol for 4-bromophenol. 1115 mp 203-205 C.; 1116 1H NMR (DMSO-d6): 9.88 (bs, 1/2H), 9.54 (bs, 1/2H), 8.32 (s, 1/2H), 7.56-8.01 (c, 5 1/2H), 7.34 (s, 1H), 7.00-7.14 (c, 4H), 4.78-4.97 (c, 1/2H), 4.34-4.50 (c, 1/2H), 4.06-4.27 (c, 2H), 3.69-3.85 (c, 1H), 3.57-3.68 (c, 1H), 2.78 (s, 3H), 1.17-1.28 (c, 6H); 1117 13C NMR(DMSO-d6): 176.5, 176.2, 163.1, 158.1, 154.2, 154.1, 128.3, 128.2, 128.0, 127.0, 126.8, 126.2, 115.2, 64.8, 60.7, 36.7, 36.4, 24.2, 21.4; 1118 MS (ESI()) 491 (MH), 508 (MNH4), 513 (MNa).

EXAMPLE 115

N-1-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1119 The title compound was prepared following the procedures of example 46, except substituting 4-trifluoromethoxybenzeneboronic acid for 4-butyloxybenzeneboronic in example 46B. 1120 mp 195-197 C.; 1121 1H NMR, (DMSO-d6): 9.62 (bs, 1H), 8.29-8.43 (c, 1H), 8.10 (s, 1/2H), 7.95-8.05 (c, 4H), 7.92 (d, 1H, J3 Hz), 7.88 (d, 1H, J3 Hz), 7.74 (s, 1/2H), 7.54 (s, 1H), 7.49 (s, 1H), 4.87-4.99 (c, 1/2H), 4.50-4.63 (c, 1/2H), 3.43-3.80 (c, 4H), 1.22 (s, 6H); 1122 13C NMR(DMSO-d6): 177.2, 177.1, 162.3, 157.1, 155.0, 154.8, 148.7, 144.0, 143.9, 138.0, 137.8, 137.5, 129.2, 128.6, 128.4, 127.9, 127.7, 121.5, 118.4, 57.8, 53.3, 53.0, 51.3, 47.5, 38.8, 38.1, 24.31, 24.30; 1123 MS (ESI()) 530 (MH), 547 (MNH4), 552 (MNa), 1076 (2MNH4), 1081 (2MNa); 1124 HRMS: Calcd: 530.120. Found: 530.1193; 1125 Anal. Calcd for: C22H22F3N3O7S C, 49.90; H, 4.19; N, 7.94; F, 10.76; S, 6.06. 1126 Found: C, 49.58; H, 4.10; N, 7.75; F, 11.04; S, 5.96.

EXAMPLE 116

N-1-4-(4-pyridinyloxy)phenylsulfonylethyl-N-hydroxyformamide

EXAMPLE 116A

4-4-(methylsulfonyl)phenoxylpyridine 1127 A mixture of 4-methylsulfonylphenol (2.93 g, 17 mmol) and 4-chloropyridine hydrochloride (2.93 g, 19.5 mmol) was heated at 150 C., resulting in a gradual melt, which was stirred at 150 C. for 4h, then partitioned between ethyl acetate and 1N NaOH. The organic extract was dried over MgSO4, filtered, and concentrated to 1.3 g of a yellow solid. The solid was recrystallized from ethyl acetate-ether to give 0.81 g of the title compound as a white solid.

EXAMPLE 116B

N-1-4-(4-pyridinyloxy)phenylsulfonylethyl-N-hydroxyformamide 1128 The tiltle compound was prepared following the procedures of examples 75, except substituting example 1 16A for 71B and acetaldehyde for propionaldehyde. 1129 mp 180-181 C.; 1130 1H NMR, 400 MHz (DMSO-d6): 9.71 (bs, 1H), 8.54 (d, 2H, J3 Hz), 8.05 (s, 1/2H), 7.97 (d, 2H, J6 Hz), 7.84 (s, 1/2H), 7.49 (d, 2H, J6 Hz), 7.03-7.13 (c, 2H), 4.63-4.73 (c, 1/2H), 4.28-4.39 (c, 1/2H), 3.59-3.78 (c, 1H),3.48 (dd, 1H, J3,10.5 Hz), 1.20 (dd, 3H, J4.5, 10.5 Hz); 1131 13C NMR (DMSO-d6): 162.62, 162.61, 161.33, 158.33, 158.31, 156.74, 151.77, 135.40, 135.13, 130.74, 130.45, 120.56, 120.34, 113.27, 56.50, 49.69, 45.02, 19.05, 17.71; 1132 MS (ESI()) 337 (MH), 359 (MNa),391 (MNaMeOH), 695 (2MNa); 1133 Anal. Calcd for: C15H16N2O5S.0.5H2O: C, 52.16; H, 4.96; N, 8.11; S, 9.28. 1134 Found: C, 52.32; H, 4.78; N, 7.98; S, 9.45.

EXAMPLE 117

N-1-(4-cyanophenoxy)phenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1135 The title compound was prepared according to the procedures of example 61, except substituting 4-(4-cyanophenoxy)benzene thiol for 4-thiol-4-biphenylcarbonitrile and example 23A for example 16B, in example 61A. 1136 1H NMR (300 MHz, d6-DMSO) 9.70 (s, 0.5H), 9.50 (s, 0.5H), 8.39 (s, 0.5H), 8.34 (s, 0.5H), 8.10 (s, 0.5H), 7.98-7.91 (m, 4H), 7.68 (s, 0.5H), 7.37-7.27 (m, 4H), 4.88-4.77 (m, 0.5H), 4.52-4.41 (m, 0.5H), 3.78-3.39 (m, 4H), 1.24-1.22 (m, 6H); 1137 MS (ESI) m/e 487 (MH); 1138 Anal. calcd for C22H22N4O7S: C, 54.31; H, 4.56. Found: C, 54.17; H, 4.79.

EXAMPLE 118

N-1-4-4-(trifluoromethoxy)phenoxyphenylsulfonylmethyl-3-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)propyl-N-hydroxyformamide 1139 The title compound was prepared according to the procedures of example 61, except substituting 4-(4-trifluoromethoxyphenoxy)benzene thiol for 4-thiol-4-biphenylcarbonitrile and example 47A for example 16B, in example 61A. 1140 1H NMR (d6-DMSO) 9.96 (s, 0.5H), 9.60 (s, 0.5H), 8.32 (s, 0.5H), 8.23 (s, 0.5H), 8.11 (s, 0.5H), 7.93-7.86 (m, 2H), 7.75 (s, 0.5H), 7.48 (d, 0.5H, J8.8 Hz), 7.25 (dd, 4H, J22.8, 8.8 Hz), 4.53-4.42 (m, 0.5H), 4.04-3.93 (m, 0.5H), 3.65-3.46 (m, 2H), 3.34-3.22 (m, 2H), 2.02-1.62 (m, 2H), 1.26 (s, 3H), 1.23 (s, 3H); 1141 MS (ESI) 560 (MH), 577 (MNH4), 582 (MNa), 558 (MH); 1142 Anal. Calcd for: C23H24N3O8SF3: C, 49.37; H, 4.32; N, 7.51. Found: C, 49.46; H, 4.23; N, 7.47.

EXAMPLE 119

N-1-4-4-(trifluoromethoxy)phenoxyphenylsulfonylmethyl-2-(4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1143 The title compound was prepared according to the procedures of example 61, except substituting 4-(4-trifluoromethoxyphenoxy)benzene thiol for 4-thiol-4-biphenylcarbonitrile in example 61A. 1144 1H NMR (d6-DMSO) 9.51 (s, 0.5H), 9.70 (s, 0.5H), 8.09 (s, 0.5H), 7.91 (dd, 2H, J8.9, 3.1 Hz), 7.68 (s, 0.5H), 7.47 (d, 2H, J9.2 Hz), 7.31-7.21 (m, 4H), 4.90-4.78 (m, 0.5H), 4.51-4.40 (m, 0.5H), 3.74-3.40 (m, 4H), 2.76 (d, 3H, J1.7 Hz), 1.27-1.22 (m, 6H); 1145 MS (ESI) 558 (MH), 560 (MH), 577 (MNH4), 582 (MNa); 1146 Anal. Caled for: C23H24N3O8SF3: C, 49.37; H, 4.32; N, 7.51. Found: C, 49.41; H, 4.29; N, 7.36.

EXAMPLE 120 1147 ()-N-hydroxy-N-1-(3-pyridinyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide 1148 The title compound was prepared according to the procedures of Example 75, except substituting 3-pyridine carboxaldehyde for propionaldehyde and 4-(4-trifluoromethylphenyl)phenyl methyl sulfone (ex. 76A) for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1149 mp 186.5-188.8 C.; 1150 MS (ESI) m/z 451 (MH), 473 (MNa), 449 (MH); 1151 1H NMR (300 MHz, DMSO-d6) 4.16-4.34 (m, 2H), 5.58 (brs, 0.5H), 5.79 (brs, 0.5H), 7.27-7.32 (dd, 1H, J4.8, 7.8 Hz), 7.78-7.98 (9H), 8.14 (brs, 0.5H), 8.27 (brs, 0.5H), 8.46-8.47 (dbrs 1.5H, J4.5 Hz), 8.60 (brs, 0.5H), 9.70 (brs, 0.5H), 10.14 (brs, 0.5H); 1152 Anal. calcd for C21H17N2F3O4S: C, 55.99; H, 3.80; N, 6.21. Found: C, 55.79; H, 3.76; N, 6.18.

EXAMPLE 121

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(4-chlorophenoxy)phenylsulfonylethylformamide 1153 The title compound was prepared according to the procedures described in Examples 77 and 78, except substituting Example 74A for Example 76A. 1154 mp 108.3-110.5 C.; 1155 MS (ESI) m/z 403 (MNH4), 420 (MCl), 384 (MH); 1156 1H NMR (300 MHz, DMSO-d6) 3.29-3.59 (m, 4H), 3.94-4.06 (m, 0.7H), 4.50-4.60 (m, 0.3H), 4.94-5.01 (m, 1H), 7.17-7.21 (dd, 4H, J3, 8.7 Hz), 7.51-7.54 (d, 2H, J8.7 Hz), 7.76 (s, 0.7H), 7.86-7.90 (2H), 8.12 (s, 0.3H), 9.39 (s, 0.7H), 9.80 (s, 0.3H); 1157 Anal. calcd for C16H16NClO6S: C, 49.80; H, 4.18; N, 3.63. Found: C, 49.51; H, 4.31; N, 3.46.

EXAMPLE 122

()-N-hydroxy-N-1-methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide 1158 The title compound was prepared according to the procedures described in Examples 71C-71E, except substituting Example 76A for Example 71A. 1159 mp 174.6-175.2 C.; 1160 MS (ESI) m/z 388 (MH), 410 (MNa), 386 (MH), 422 (MCl); 1161 1H NMR (300 MHz, DMSO-d6) 1.16-1.24 (dd, 3H, J6.3, 17.7 Hz), 3.49-3.56 (dd, 1H, J4.2, 14.4 Hz), 3.61-3.74 (m, 1H), 4.30-4.43 (m, 0.5H), 4.64-4.78 (m, 0.5H), 7.87-8.07 (9H), 9.48 (brs, 0.5H); 1162 Anal. calcd for C17H16NF3O4S: C, 52.71; H, 4.16; N, 3.61. Found: C, 52.74; H, 4.23; N, 3.57.

EXAMPLE 123

()-N-hydroxy-N-1-(2-pyridinyl)-2-4-(trifluoromethyl) 1,1-biphenyl-4-ylsulfonylethylformamide 1163 The title compound was prepared according to the procedures of Example 75, except substituting 2-pyridine carboxaldehyde for propionaldehyde and 4-(4-trifluoromethylphenyl)phenyl methyl sulfone (ex. 76A) for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1164 mp 168.5-168.9 C.; 1165 MS (ESI) m/z 451 (MH), 473 (MNa), 449 (MH), 485 (MCl); 1166 1H NMR (300 MHz, DMSO-d6) 3.98-4.12 (m, 1H), 4.36-4.42 (d, 1H, J15.3 Hz), 5.57 (br, 0.5H), 5.89 (br, 0.5H), 7.28-7.33 (m, 1.5H), 7.41-7.44 (d, 0.5H, J6.9 Hz), 7.73-7.83 (m, 1H), 7.87-7.90 (2H), 7.97-7.80 (m, 6H), 8.25 (s, 1H), 8.45 (br, 1H), 9.69 (s, 0.5H), 10.07 (s, 0.5H); 1167 Anal. calcd for C21H17N2F3O4S: C, 55.99; H, 3.80; N, 6.21. Found: C, 55.88; H, 3.61; N, 6.17.

EXAMPLE 124

()-N-1-(4,4-dimethyl-2,6-dioxo-1-piperidinyl)methyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 1168 The title compound was prepared using the following sequence of reactions (i) alkylation of epibromohydrin with 3,3-dimethylglutarimide in the presence of potassium carbonate in methanol (ii) opening the resulting epoxide with 4-bromothiophenol as in Example 2B in the presence of potassium carbonate (iii) alcohol oxidation to the ketone as in Example 2C (iv) coupling the resulting ketone with 4-trifluorobenzene boronic acid, as in Example 46B and (v) converting the resulting ketone to the title compound following the procedures of Examples 46C-D. 1169 mp 185.6-187.3 C.; 1170 MS (APCI) m/z 527 (MH), 544 (MNH4), 561 (MCl); 1171 1H NMR (300 MHz, DMSO-d6) 0.927-0.935 (ss, 6H), 3.443-3.538 (m, 1H), 3.652-3.784 (m, 2H), 3.884-3.993 (m, 1H), 4.390-4.416 (m, 0.5H), 4.916-4.945 (m, 0.5H), 7.765 (s, 0.5H), 7.882-7.910 (2H), 7.987-8.065 (m, 6.5H), 9.523 (s, 0.5H), 9.660 (s, 0.5H); 1172 Anal. calcd for C24H25N2F3O6S.0.25 hexanes : C, 55.88; H, 5.24; N, 5.1 1. Found: C, 55.65; H, 5.15; N, 5.02.

EXAMPLE 125

()-N-hydroxy-N-3-hydroxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethylpropylformamide

EXAMPLE 125A

()-N-3-(1,1-dimethylethyl)dimethylsilyloxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethylpropyl-N-hydroxyformamide 1173 The title compound was prepared according to the procedures of Example 75, except substituting 3-tert-butuldimethylsilyloxy-propionaldehyde for propionaldehyde and 4-(4-trifluoromethylphenyl)phenyl methyl sulfone (Example 76A) for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A.

EXAMPLE 125B

()-N-hydroxy-N-3-hydroxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethylpropylformamide 1174 A solution of 125A (488 mg, 0.92 mmol) in THF (20 mL) at 0 C. was treated with TBAF (1.0M/THF, 1.84 mL, 1.84 mmol), stirred at 0 C. for one hour, treated with water, extracted with ethyl acetate, dried (Na2SO4), concentrated and triturated sequentially with ethyl ether and dichloromethane to provide 257 mg (67%) of the title compound as an off-white solid. 1175 mp 186.5-188.8 C.; 1176 MS (APCI) m/z 418 (MH), 435 (MNH4), 452 (MCl); 1177 1H NMR (300 MHz, DMSO-d6) 1.56-1.82 (m, 2H), 3.51-3.57 (dd, 1H, J3, 15 Hz), 3.63-3.76 (m, 1H), 4.26-4.38 (m, 0.5H), 4.50-4.51 (br, 0.7H), 4.52-4.53 (m, 0.3H), 7.81-8.09 (9H), 9.48 (br, 0.5H); 1178 Anal. calcd for C18H18NF3O5S: C, 51.79; H, 4.34; N, 3.35. Found: C, 51.77; H, 4.50; N, 3.28.

EXAMPLE 126

()-N-hydroxy-N-1-(methoxymethyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide

EXAMPLE 126A

1-methoxy-3-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-2-propanone 1179 A solution of 4-(4-trifluoromethylphenyl)phenyl methyl sulfone (1.0 g, 3.33 mmol) in THF (50 mL) at 1180 78 C. was treated with n-butyllithium (2.5M/hexanes, 1.4 mL, 3.50 mmol), stirred at 1181 78 C. for 1.5 hours and then treated with ethyl methoxyacetate (0.78 mL, 6.66 mmol), stirred at 78 C. for three hours, treated with saturated NH4Cl solution, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), concentrated and purified on silica gel with 30-50% ethyl acetate/hexanes to provide 902 mg (73%) of the title compound as a white solid. 1182 MS (APCI) m/z 390 (MNH4), 371 (MH), 470 (MCl).

EXAMPLE 126B

()-1-methoxy-3-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonyl-2-propanol 1183 A suspension of Example 126A (850 mg, 2.28 mmol) in ethanol (100 mL) at ambient temperature was treated with sodium borohydride (103 mg, 2.74 mmol), stirred for 30 minutes, treated with water, extracted with ethyl acetate, dried (Na2SO4) and concentrated to provide 820 mg (96%) of the title compound as a white solid. 1184 MS (APCI) m/z 392 (MNH4), 409 (MCl).

EXAMPLE 126C

()-N-hydroxy-N-1-(methoxymethyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide 1185 Example 126B was converted to the title compound following the procedures of Examples 75C and 75D. 1186 mp 175.3-176.3 C.; 1187 MS (ESI) m/z 418 (MH), 435 (MNH4), 440 (MNa), 416 (MH); 1188 1H NMR (300 MHz, DMSO-d6) 3.17 (s, 1.5H), 3.21 (s, 1.5H), 3.41-3.51 (m, 2H), 3.63-3.68 (m, 1H), 4.28 (m, 0.5H), 4.80 (m, 0.5H), 7.87-7.90 (2.5H), 7.98-8.03 (6H), 8.14 (s, 0.5H), 9.54 (br s, 0.5H), 9.94 (0.5H); 1189 Anal. calcd for C18H18NF3O5S: C, 51.79; H, 4.34; N, 3.35. Found: C, 51.57; H, 4.50; N, 3.31.

EXAMPLE 127

()-N-1-(1,3-benzodioxol-5-yl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 1190 The title compound was prepared according to the procedures of Example 75, except substituting piperonal for propionaldehyde and 4-(4-trifluoromethylphenyl)-phenyl methyl sulfone (ex. 76A) for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1191 mp 159.5-160.5 C.; 1192 MS (ESI) m/z 516 (MNa), 492 (MH), 528 (MCl); 1193 1H NMR (300 MHz, DMSO-d6) 4.02-4.18 (br, 2H), 5.30-5.40 (br, 0.5H), 5.60-5.70 (br, 0.5H), 5.85 (s, 0.5H), 5.92 (s, 0.5H),6.77-6.93 (3H), 7.88-7.98 (m, 8H), 8.09-8.10 (br, 0.5H), 8.19-8.22 (br, 0.5H), 9.52-9.64 (br, 0.5H), 9.94-10.10 (br, 0.5H); 1194 Anal. calcd for C23H18N2F3O6S: C, 55.98; H, 3.67; N, 2.83. Found: C, 55.86; H, 3.65; N, 2.79.

EXAMPLE 128

()-N-hydroxy-N-4-hydroxy-1-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylmethylbutylformamide 1195 The title compound was prepared according to the procedures of Example 125, except substituting 4-tert-butyldimethylsilyloxybutanaldehyde for 3-tert-butyldimethylsilyloxypropionaldehyde. 1196 mp 138.9-140.3 C.; 1197 MS (ESI) m/z 432 (MH), 454 (MNa), 466 (MCl); 1198 1H NMR (300 MHz, DMSO-d6) 1.22-1.36 (m, 2H), 1.44-1.66 (m, 2H), 3.47-3.54 (1H), 3.62-3.71 (m, 1H), 4.10-4.20 (m, 0.6H), 4.39-4.44 (m, 1H), 4.52-4.62 (m, 0.4H), 7.88-8.13 (10H), 9.47 (s, 0.6H), 9.85 (s, 0.4H); 1199 Anal. calcd for C19H20N2F3O5S: C, 52.89; H, 4.67; N, 3.24. Found: C, 53.26; H, 5.00; N, 3.25.

EXAMPLE 129

()-N-hydroxy-N-1-4-(methoxymethoxy)phenyl-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide 1200 The title compound was prepared according to the procedures of Example 75, except substituting 4-(methoxymethoxy)benzaldehyde for propionaldehyde and 4-(4-trifluoromethylphenyl)-phenyl methyl sulfone (ex. 76A) for 4-(4-methoxylphenyl)-phenyl methyl sulfone in Example 75A. 1201 mp 137.1-138.5 C.; 1202 MS (ESI) m/z 527 (MNH4), 508 (MH), 544 (MCl); 1203 1H NMR (300 MHz, DMSO-d6) 3.28 (s, 3H), 4.00-4.20 (2H), 5.12 (s, 2H),5.40 (br, 0.5H), 5.60 (br, 0.5H), 6.88-6.91 (d, 2H, J8.7 Hz), 7.18-7.32 (m, 2H), 7.87-7.99 (m, 8H), 8.09 (br, 0.5H), 8.22 (br, 0.5H), 9.58 (s, 0.5H), 10.02 (s, 0.5H); 1204 Anal. calcd for C24H22NF3O6S: C, 56.57; H, 4.35; N, 2.74. Found: C, 56.59; H, 4.50; N, 2.70.

EXAMPLE 130

()-N-hydroxy-N-1-(1-methyl-1H-pyrrol-2-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1205 The title compound was prepared according to the procedures of Example 75, except substituting 2-N-Methylpyrrole carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1206 MS (ESI) MH (483); 1207 1H NMR (300 MHz, DMSO-d6) 9.90 (s, 1H), 9.51 (s, 1H), 8.07 (s, 1H), 7.87-7.83 (d, 2H, J8.9 Hz), 7.49-7.46 (d, 2H, J8.4 Hz), 7.27-7.24 (d, 2H, J8.8 Hz), 7.17-7.14 (d, 2H, J8.8 Hz), 6.65 (s, 1H), 6.02 (s, 1H), 5.85-5.79 (m, 1H), 4.04-3.87 (mm, 2H), 3.53-3.44 (m, 3H); 1208 Anal. calcd for C21H19N2O6SF3: C, 52.06; H, 3.95; N, 5.78. Found: C, 52.42; H, 4.12; N, 5.48.

EXAMPLE 131

()-N-hydroxy-N-1-phenyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1209 The title compound was prepared according to the procedures of Example 75, except substituting benzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1210 MS (ESI) MH (480); 1H NMR (300 MHz, DMSO-d6) 10.06 (s, 0.5H), 9.96 (s, 0.5H), 8.18-8.11 (m, 1H), 7.87-7.85 (m, 2H), 7.50-7.47 (d, 2H, J8.8 Hz), 7.30-7.24 (m, 5H), 7.15-7.13 (d, 2H, J8.5 Hz), 5.78 (s, 0.5H), 5.41 (s, 0.5H), 4.24-4.04 (mm, 3H); 1211 Anal. calcd for C22H18NO6SF3: C, 54.88; H, 3.76; N, 2.90. Found: C, 54.58; H, 3.89; N, 2.96.

EXAMPLE 132

()-N-hydroxy-N-1-(2-thienyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1212 The title compound was prepared according to the procedures of Example 75, except substituting 2-thiophene carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1213 MS (ESI) MH (486); 1214 1H NMR (300 MHz, DMSO-d6) 10.15 (s, 0.5H), 9.75 (s, 0.5H), 8.16-8.12 (m, 1H), 7.88-7.85 (d, 2H, J8.1 Hz), 7.50-7.47 (m, 2H), 7.29-7.25 (d, 2H, J8.2 Hz), 7.17-7.14 (d, 2H, J8.8 Hz), 7.08-7.04 (m, 1H), 6.95-6.92 (m, 1H), 5.92 (s, 0.5H), 5.76 (m, 0.5H), 4.05-4.00 (m, 3H); 1215 Anal. calcd for C20H16NO6S2F3: C, 49.27; H, 3.30; N, 2.87. Found: C, 49.01; H, 3.24; N, 2.75.

EXAMPLE 133

()-N-1-(2-furanyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1216 The title compound was prepared according to the procedures of Example 75, except substituting 2-furyl carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1217 MS (ESI) MH (470); 1218 1H NMR (300 MHz, DMSO-d6) 10.03 (s, 0.5H), 9.60 (s, 0.5H), 8.14 (s, 1H), 7.90-7.89 (m, 2H), 7.57 (s, 1H), 7.49-7.46 (d, 2H, J8.5 Hz), 7.29-7.25 (d, 2H, J8.5 Hz), 7.19-7.16 (d, 8.5H), 6.41 (s, 1H), 6.39 (s, 1H), 4.04-4.00 (m, 3H); 1219 Anal. calcd for C20H16NO7SF3: C, 50.95; H, 3.42; N, 2.97. Found: C, 51.25; H, 3.70; N, 2.99.

EXAMPLE 134

()-N-1-(5,5-dimethyl-2,4-dioxo-3-oxazolidinyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide

EXAMPLE 134A

1-bromo-3-4-(trifluoromethoxy)1,1-biphenyl-4-yloxy-2-propanone 1220 The title compound was prepared from 3-(4-(4-trifluoromethoxyphenyl)phenoxy)propan1,2oxirane using the procedure described in Example 47A.

EXAMPLE 134B

()-N-1-(5,5-dimethyl-2,4-dioxo-3-oxazolidinyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethyl-N-hydroxyformamide 1221 Example 134B was converted to the tile compound by first reacting with 5,5-dimethyloxazolidinine-2,4-dione as in Example 3C, then applying the sequence of reactions described in Examples 2D, 2E and 2F. 1222 1H NMR (300 MHz, DMSO-d6) 10.09 (s, 0.5H), 9.71 (s, 0.5H), 8.34 (s, 0.5H), 7.98 (s, 0.5H), 7.76-7.73 (d, 2H, J8.8 Hz), 7.65-7.63 (d, 2H, J8.5 Hz), 7.43-7.40 (d, 2H, J8.8 Hz), 7.05-7.02 (d, 2H, J8.8 Hz), 4.90-4.88 (m, 0.5H), 4.44-4.40 (m, 0.5H), 4.22-4.15 (m, 2H), 3.86-3.68 (m, 1H), 3.66-3.59 (m, 1H), 1.49 (s, 6H); 1223 Anal. calcd for C22H21N2O7F3.0.25 ethyl acetate; C, 54.76; H, 4.59; N, 5.55. Found: C, 54.91; H, 4.49; N, 5.44.

EXAMPLE 135

()-N-hydroxy-N--(methoxymethyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1224 The title compound was prepared according to the procedures of Example 126, except substituting 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1225 MS (ESI) 448 (MH); 1226 1H NMR (300 MHz, DMSO-d6) 3.20 (s, 3H), 3.23-3.45 (m, 3H), 3.52-3.65 (m, 1H), 4.16-4.27 (m, 0.5H), 4.70-5.02 (m, 0.5H), 7.21 (dd, 2H, J3,9 Hz), 7.28 (dd, 2H, J6,9 Hz), 7.47 (d, 2H, J9 Hz), 7.81 (s, 0.5H), 7.90 (dd, 2H, J3,9 Hz), 8.12 (s, 0.5H), 9.56 (bs, 0.5H), 9.91 (bs, 0.5H); 1227 Anal. calcd for C18H18NO7SF3.0.25 ethyl acetate: C, 48.40; H, 4.27; N, 2.97. Found: C, 48.61; H, 4.33; N, 3.06.

EXAMPLE 136

(S)-N-hydroxy-N-1-(phenylmethoxy)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethylformamide 1228 The title compound was prepared from Example 108B following the procedures of Examples 108E and 108F. 1229 MS (ESI) 460 (MH); 1230 1H NMR (300 MHz, DMSO-d6) 3.58-3.73 (m, 2H), 4.0-4.2 (m, 2H), 4.28-4.35 (m, 0.5H), 4.55 (s, 2H), 4.8-4.9 (m, 0.5H), 7.03 (d, 2H, J9 Hz), 7.25-7.38 (m, 5H), 7.43 (d, 2H, J9 Hz), 7.63 (d, 2H, J9 Hz), 7.75 (d, 2H, J9 Hz), 8.06 (s, 0.5H), 8.42 (s, 0.5H), 9.62 (s, 0.5H), 10.03 (s, 0.5H); 1231 Anal. calcd for C24H22F3NO5: C, 62.47; H, 4.80; N, 3.03. Found: C, 62.29; H, 5.03; N, 2.92.

EXAMPLE 137

(S)-N-hydroxy-N-1-(hydroxymethyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethylformamide 1232 The title compound was prepared from Example 108B following the procedures of Examples 108C, 108E and 108F. 1233 MS (ESI) 370 (MH); 1234 1H NMR (300 MHz, DMSO-d6) 3.45-3.53 (m, 2H), 3.95-4.20 (m, 2.5H), 4.55-4.68 (m, 0.5H), 4.90-4.98 (m, 1H), 7.05 (d, 2H, J9 Hz), 7.42 (d, 9H), 7.64 (d, 2H, J9 Hz), 7.75 (d, 2H, J9 Hz), 7.98 (s, 0.5H), 8.39 (s, 0.5H), 9.47 (s, 0.5H), 9.89 (s, 0.5H); 1235 Anal. calcd for C17H16F3NO5: C, 54.99; H, 4.34; N, 3.77. Found: C, 54.77; H, 4.57; N, 3.54.

EXAMPLE 138

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1236 The title compound was prepared according to the procedures of Example 125, except substituting t-butyldimethylsilyloxy-acetaldehyde for 3-tert-butyldimethylsilyloxy-propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-tri-fluoromethylphenyl)phenyl methyl sulfone. 1237 mp 115-117 C.; 1238 MS (ESI) 436 (MH), 453 (MNH4), 458 (MNa); 1239 1H NMR (300 MHz, DMSO-d6) 3.30-3.62 (m, 4H), 3.93-4.03 (m, 0.5H), 4.51-4.61 (m, 0.5H), 4.95-5.06 (m, 1H), 7.22 (d, 2H, J9.0 Hz), 7.25-7.32 (m, 2H), 7.48 (d, 2H, J9.0 Hz), 7.76 (s, 0.5H), 7.86-7.94 (m, 2H), 8.13 (s, 0.5H), 9.41 (bs, 0.5H), 9.82 (bs, 0.5H); 1240 Anal. calcd for C17H16NO7SF3: C, 46.89; H, 3.70; N, 3.21. Found: C, 46.65; H, 3.71; N, 3.14.

EXAMPLE 139

S-(R*,S*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide

EXAMPLE 139A AND 139B

S-(R*,S*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylhydroxylamine

139B

S-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-r4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylhydroxylamine 1241 The title compounds were prepared as a diastereomeric mixture according to the procedures of Examples 75A, 75B and 75C, except substituting (R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. The two distereomers were separated via silica gel choromatography to give Example 139A and Example 139B.

EXAMPLE 139C

S-(R*,S*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1242 Example 139A was converted to the title compound following the formylation procedure described in Example 1E. 1243 mp 149-150 C.; 1244 MS (ESI) 506 (MH), 523 (MNH4), 528 (MNa); 1245 1H NMR (300 MHz, DMSO-d6) 1.04 (s, 1.5H), 1.13 (s, 1.5H), 1.20 (s, 1.5H), 1.23 (s, 1.5H), 3.57-4.11 (m, 5.5H), 4.39 (t, 0.5H, J9.80 Hz), 7.19-7.30 (m, 4H), 7.49 (d, 2H, J8.70 Hz), 7.86-7.97 (m, 2.5H), 8.15 (s, 0.5H), 9.71 (bs, 0.5H), 10.20 (s, 0.5H); 1246 Anal. calcd for C21H22NO8SF3: C, 49.90; H, 4.38; N, 2.77. Found: C, 49.90; H, 4.35; N, 2.52.

EXAMPLE 140

S-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1247 Example 139B was converted to the title compound following the formylation procedure described in Example 1 E. 1248 mp 127-128 C.; 1249 MS (ESI) 506 (MH), 523 (MNH4), 528 (MNa); 1250 1H NMR (300 MHz, DMSO-d6) 1.21 (s, 1.5H), 1.23 (s, 1.5H), 1.26 (s, 1.5H), 1.30 (s, 1.5H), 3.28-3.40 (m, 1H), 3.61-3.73 (m, 2H), 3.92-4.14 (m, 2.5H), 4.56 (t, 0.5H, J8.25 Hz), 7.20-7.31 (m, 4H), 7.48 (d, 2H, J8.70 Hz), 7.81 (s, 0.5H), 7.92 (t, 2H, J9.0 Hz), 8.13 (s, 0.5H), 9.63 (bs, 0.5H), 10.01 (bs, 0.5H); 1251 Anal. calcd for C21H22NO8SF3: C, 49.90; H, 4.38; N, 2.77. Found: C, 49.96; H, 4.46; N, 2.76.

EXAMPLE 141

S-(R*,R*)-N-(2,3-dihydroxy)-1-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylmethylpropyl-N-hydroxyformamide

EXAMPLE 141A

S-(R*,R*)-3-(hydroxyamino)-4-4-(trifluoromethoxy)phenoxyphenylsulfonyl-1,2-butanediol 1252 Example 139B (9.6 gm, 20 mmol) was dissolved in THF (300 mL) and treated with 3N HCl (40 mL) dropwise, and the clear solution was stirred at 45 C. for 1 hr. The reaction mixture was neutralized with a slow addition of NaHCO3 solution and extracted with ether. The organic layer was dried with MgSO4 and concentrated to white solid. Recrystallization from CH2Cl2 afforded pure title compound as a white powder (6.94 gm, 79%). 1253 MS (ESI) 439 (MH).

EXAMPLE 141B

S-(R*,R*)-N-(2,3-dihydroxy)-1-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylmethylpropyl-N-hydroxyformamide 1254 Example 141A was converted to the title compound following the formylation procedure described in Example 1E. 1255 mp 137-138 C.; 1256 MS (ESI) 466 (MH), 483 (MNH4), 488 (MNa); 1257 1H NMR (300 MHz, DMSO-d6) 3.30-3.60 (m, 3H), 3.65-3.78 (m, 1H), 3.90-3.99 (m, 0.5H), 4.53-4.62 (m, 0.5H), 4.78 (bs, 1H), 4.94 (bs, 1H), 7.21 (d, 2H, J9.0 Hz), 7.25-7.32 (m, 2H), 7.47 (d, 2H, J8.60 Hz), 7.70 (s, 0.5H), 7.84-7.92 (m, 2H), 8.09 (s, 0.5H), 9.30 (bs, 0.5H), 9.65 (bs, 0.5H); 1258 Anal. calcd for C18H18NO8SF3: C, 46.45; H, 3.89; N, 3.00. Found: C, 46.29; H, 3.88; N, 2.91; 1259 D4.2 (MeOH).

EXAMPLE 142

()-N-1-(dimethylamino)methyl-2-4-4-(trifluoromethoxy)phenoxyphenyl-sulfonylethyl-N-hydroxyformamide 1260 The title compound was prepared according to the procedures of Example 126, except substituting 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone and N,N-dimethylglycine ethyl ester for ethyl methoxyacetate. 1261 MS (ESI) 463 (MH), 485 (MNa); 1262 1H NMR (300 MHz, DMSO-d6) 2.04 (s, 3H), 2.10 (s, 3H), 2.21-2.39 (m, 2H), 3.40-3.48 (m, 1H), 3.53-3.63 (m, 1H), 4.05-4.17 (m, 0.5H), 4.62-4.72 (m, 0.5H), 7.19-7.30 (m, 4H), 7.47 (d, 2H, J9.0 Hz), 7.86 (s, 0.5H), 7.87-7.94 (m, 2H), 8.10 (s, 0.5H), 9.45 (bs, 0.5H), 9.85 (bs, 0.5H); 1263 Anal. calcd for C19H21N2O6F3S: C, 49.34; H, 4.57; N, 6.05. Found: C, 49.12; H, 4.72; N, 6.04.

EXAMPLE 143

S-(R*,R*)-N-2-(4-chloro1,1-biphenyl-4-yl)sulfonyl-1-(2,2-dimethyl-1,3-dioxol-4-yl)ethyl-N-hydroxyformamide 1264 The title compound was prepared according to the procedures described for Examples 139 and 140, starting with 4-(4-chlorophenyl)phenyl methyl sulfone and (R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde. 1265 MS (ESI) 440 (MH), 457 (MNH4); 1266 1H NMR (300 MHz, DMSO-d6) 1.20 (s, 1.5H), 1.22 (s, 1.5H), 1.26 (s, 1.5H), 2.30 (s, 1.5H), 3.32-3.40 (m, 1H), 3.62-3.78 (m, 2H), 3.93-4.15 (m, 2.5H), 4.64 (t, 0.5H, J8.4 Hz), 7.58 (d, 2H, J8.4 Hz), 7.77-7.83 (m, 2H), 7.89 (s, 0.5H), 7.93-8.02 (m, 4H), 8.13 (s, 0.5H), 9.62 (bs, 0.5H), 9.97 (bs, 0.5H); 1267 Anal. calcd for C20H22NO6SCI: C, 54.60; H, 5.04; N, 3.18. Found: C, 54.48; H, 5.30; N, 3.13.

EXAMPLE 144

()-N-1-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyl-N-hydroxyformamide 1268 The title compound was prepared according to the procedures described in Example 134, except substituting saccharin for 5,5-dimethyloxazolidinine-2,4-dione. 1269 MS (ESI) 535 (M1); 1270 1H NMR (300 MHz, DMSO-d6) 3.9-4.2 (m, 2H), 4.2-4.3 (m, 2H), 4.45-4.55 (m, 0.5H), 5.0-5.1 (m, 0.5H), 7.0-7.1 (m, 2H), 7.42 (d, 2H, J8.4 Hz), 7.64 (d, 2H, J8.4 Hz), 7.74 (d, 2H, J9.0 Hz), 8.0-8.2 (m, 3.5H), 8.3-8.4 (m, 1.5H), 9.78 (s, 0.5H), 10.14 (s, 0.5H); 1271 Anal. calcd for C24H19F3N2O7S: C, 53.73; H, 3.56; N, 5.22. Found: C, 53.81; H, 3.78; N, 5.07.

EXAMPLE 145

R-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide

EXAMPLE 145A AND 145B

R-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylhydroxylamine

145B

R-(S*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylhydroxylamine 1272 The title compounds were prepared as a diastereomeric mixture according to the procedures of Examples 126A, 126B,75A and 75B and 75C, starting with 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone and methyl (S)-2,2-dimethyl-1,3-dioxolane-4-carboxylate. The two distereomers were separated via silica gel chromatography to give Example 145A and Example 145B.

EXAMPLE 145C

R-(R*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1273 Example 145A was converted to the title compound following the formylation procedure described in Example 1E. 1274 MS (ESI) 506 (M1), 523 (M18); 1275 1H NMR (300 MHz, DMSO-d6) 1.21 (s, 1.5H), 1.23 (s, 1.5H), 1.26 (s, 1.5H), 1.30 (s, 1.5H), 3.3-3.4 (m, 1H), 3.60-3.75 (m, 2H), 3.9-4.1 (m, 2.5H), 4.5-4.6 (m, 0.5H), 7.2-7.3 (m, 4H), 7.48 (d, 2H, J8.7 Hz), 7.81 (s, 0.5H), 7.85-7.95 (m, 2H), 8.13 (s, 0.5H), 9.63 (br s, 0.5H), 10.0 (br s, 0.5H); 1276 Anal. calcd for C21H22F3NO8S: C, 49.90; H, 4.38; N, 2.77. Found: C, 49.90; H, 4.51; N, 2.66.

EXAMPLE 146

R-(S*,R*)-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1277 Example 145B was converted to the title compound following the formylation procedure described in Example 1E. 1278 MS (ESI) 506 (MH), 523 (M18); 1279 1H NMR (300 MHz, DMSO-d6) 1.05 (s, 1.5H), 1.14 (s, 1.5H), 1.20 (s, 1.5H), 1.23 (s, 1.5H), 3.3-3.4 (m, 1H), 3.5-4.1 (m, 4.5H), 4.3-4.4 (m, 0.5H), 7.2-7.3 (m, 4H), 7.48 (d, 2H), 7.8-8.0 (m, 2.5H), 8.15 (s, 0.5H), 9.68 (br s, 0.5H), 10.10 (br s, 0.5H).

EXAMPLE 147

S-(R*,R*)-N-1-(2,2-diethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxy-phenylsulfonylethyl-N-hydroxyformamide 1280 The title compound was prepared according to the procedures described for Examples 139 and 140, except substituting (R)-2,2-diethyl-1,3-dioxolane-4-carboxaldehyde for (R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde. 1281 MS (ESI) 534 (MH), 551 (M18); 1H NMR (300 MHz, DMSO-d6) 0.7-0.8 (m, 6H), 1.4-1.6 (m, 4H), 3.2-3.3 (m, 1H), 3.45-3.55 (m, 1H), 3.69 (dd, 1H, J8.7,15.6 Hz), 3.95-4.15 (m, 2.5H), 4.5-4.6 (m, 0.5H), 7.2-7.3 (m, 4H), 7.47 (d, 2H, J8.4 Hz), 7.81 (s, 0.5H), 7.85-7.95 (m, 2H), 8.14 (s, 0.5H), 9.66 (br s, 0.5H), 10.11 (br s, 0.5H); 1282 Anal. calcd for C23H26NO8SF3: C, 51.77; H, 4.91; N, 2.62. Found: C, 51.98; H, 5.12; N, 2.63.

EXAMPLE 148

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylsulfonyl)1,1-biphenyl-4-ylsulfonylethylformamide 1283 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxy-acetaldehyde for 3-tert-butyldimethylsilyloxy-propionaldehyde and 4-(4-methylsulfonylphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1284 mp 165-167 C.; 1285 MS (ESI()) 412 (MH), 825 (2MH), 847 (2MNa2H); 1286 1H NMR (300 MHz, DMSO-d6): 8.23 (s, 1/2H), 7.97-8.13 (m, 9H), 7.93 (s, 1/2H), 4.75-4.84 (m, 1H), 4.17-4.35 (m, 1H), 3.57-3.84 (m, 3H), 3.41-3.53 (m, 1H), 3.18 (s, 3H); 1287 HRMS: calc: 414.0681, Found: 414.0668; 1288 Anal. calcd for C17H19NO7S2: C, 49.38; H, 4.63; N, 3.38;S, 15.50. Found: C, 34.24; H, 3.47; N, 2.32; S, 14.61.

EXAMPLE 149

()-N-1-4-(1,3-benzodioxol-5-yl)phenylsulfonylmethyl-2-hydroxyethyl-N-hydroxyformamide 1289 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxyacetaldehyde for 3-tert-butyldimethyl-silyloxypropionaldehyde and 4-(3,4-methylenedioxyphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1290 mp 160-161 C.; 1291 MS (APCI) 380 (MH), 397 (MNH4); 1292 1H NMR (300 MHz, DMSO-d6): 9.42-9.83 (m, 1H), 8.19 (s, 1/2H), 7.85-8.00 (m, 4.5H), 7.49 (s, 1H), 7.41 (d, 1H, J8 Hz), 7.08 (d, 1H, J8 Hz), 6.13 (s, 2H), 4.96-5.27 (m, 1H), 4.52-4.62 (m, 1/2H), 4.04-4.14 (m, 1/2H), 3.60-3.70 (m, 2H), 3.38-3.46 (m, 2H); 1293 Anal. calcd for C17Hl7NO7S: C, 53.82; H, 4.51; N, 3.69;S, 8.45. Found: C, 53.49; H, 4.54; N, 3.58; S, 8.32.

EXAMPLE 150

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylthio)1,1-biphenyl-4-ylsulfonylethylformamide 1294 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxyacetaldehyde for 3-tert-butyldimethyl-silyloxypropionaldehyde and 4-(4-thiomethylphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1295 mp 161-162 C.; 1296 MS (DCI): 382 (MH), 399 (MNH4); 1297 1H NMR (300 MHz, DMSO-d6) 9.77-10.05 (m, 1/2H), 9.27-9.68 (m, 1/2H), 8.15 (s, 1/2H), 7.89-7.99 (m, 4H), 7.84 (s, 1/2H), 7.72 (s, 1H), 7.70 (s, 1H), 7.58 (s, 1H), 7.56 (s, 1H), 4.98-5.12 (m, 1H), 4.58-4.70 (m, 1/2H), 4.01-4.10 (m, 1/2H), 3.57-3.67 (m, 1.5H), 3.35-3.44 (m, 2H), 3.09-3.19 (m, 1/2H); 1298 HRMS: calc: 382.0783. Found: 382.0784; 1299 Anal. calcd for C17H19NO5S2.0.25 C4H8O2: C, 53.58; H, 5.25; N, 3.47; S, 15.90. Found: C, 53.77; H, 5.50; N, 3.63; S, 16.02.

EXAMPLE 151

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethylformamide 1300 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxyacetaldehyde for 3-tert-butyldimethyl-silyloxypropionaldehyde and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1301 mp 167-168 C.; 1302 MS (APCI) 420 (MH), 437 (MNH4); 1303 1H NMR (300 MHz, DMSO-d6): 9.85-9.98 (m, 1/2H), 9.41-9.58 (m, 1/2H), 8.18 (s, 1/2H), 7.98-8.07 (m, 3.5H), 7.86-7.97 (m, 3H), 7.56 (s, 1H), 7.53 (s, 1H), 5.03-5.14 (m, 1H), 4.62-4.73 (m, 1H), 4.06-4.17 (m, 1H), 3.64-3.74 (m, 1H), 3.40-3.47 (m, 2H); 1304 HRMS: calc: 420.0729. Found: 420.0722; 1305 Anal. calcd for C17H16F3NO6S: C, 48.68; H, 3.84; F, 13.59; N, 3.33; S, 7.64. Found: C, 48.54; H, 4.00; F, 13.67; N, 3.20; S, 7.95.

EXAMPLE 152

()-N-hydroxy-N-1-(hydroxymethyl)-2-(4chloro1,1-biphenyl-4-yl)sulfonylethylformamide 1306 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxyacetaldehyde for 3-tert-butyldimethyl-silyloxypropionaldehyde and 4-(4-chlorophenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1307 mp 153-154 C.; 1308 MS (ESI()) 370 (MH), 387 (MNH4), 392 (MNa); 1309 1H NMR (300 MHz, DMSO-d6): 9.34-9.92 (m, 1H), 8.19 (s, 1/2H), 7.95-8.09 (m, 4H), 7.78-7.93 (m, 2.5H), 7.56-7.68 (m, 2H), 4.94-5.21 (m, 1H), 4.62-4.73 (m, 1H), 4.05-4.16 (m, 1H), 3.62-3.74 (m, 2H), 3.52-3.56 (m, 1H); 1310 HRMS: calc: 370.0516. Found: 370.0526; 1311 Anal. calcd for C16H16ClNO5S.0.25 H2O: C, 51.33; H, 4.44; Cl, 9.47; N, 3.74; S, 8.56. 1312 Found: C,51.30; H, 4.37; Cl, 9.33; N, 3.72; S, 8.43.

EXAMPLE 153

()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoromethyl)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1313 The title compound was prepared according to the procedures of Example 61, except substituting 4-(4-trifluoromethylphenoxy)benzenethiol in place of 4-thiol-4-biphenylcarbonitrile in Example 61A. 1314 mp 141-143 C.; 1315 MS (ESI()) 544 (MH), 561 (MNH4), 566 (MNa), 1104 (2MN H4), 1109 (2MNa); 1316 1H NMR (300 MHz, DMSO-d6): 9.78 (bs, 1/2H), 9.58 (bs, 1/2H), 8.15 (s, 1/2H), 7.96-8.03 (m, 2H), 7.84-7.90 (m, 2H), 7.74 (s, 1/2H), 7.34-7.41 (m, 4H), 4.86-4.95 (m, 1/2H), 4.49-4.58 (m, 1/2H), 4.10 (s, 1/2H), 3.50-3.82 (m, 3.5H), 2.82 (s, 3H), 1.36-1.44 (m, 6H); 1317 Anal. calcd for C23H24F3N3O7S.0.25 C4H8O2: C, 50.97; H, 4.63; N, 7.43; S, 5.66; 1318 Found: C, 50.75; H, 4.73; N, 7.27; S, 5.60.;

EXAMPLE 154

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylsulfonyl)phenoxyphenylsulfonylethylformamide

EXAMPLE 154A

()-1-(1,1-dimethylethyl)dimethylslyloxy-3-4-4-(methylthio)phenoxyphenylthiol-2-propanone 1319 Reaction of 4-(4methylsulfonephenoxy)benzenethiol with 3-(tert-butyldimethylsilyloxy)propan-1,2oxirane followed by Dess Martin oxidation as described in Examples 2B and 2C afforded the title compound.

EXAMPLE 154B

()-N-hydroxy-N-1-(hydroxymethyl)-2-4-(methylsulfonyl)phenoxy-phenylsulfonylethylformamide 1320 The title compound was prepared from Example 154A, following the procedures described in Examples 61B and 61C. 1321 MS (ESI) 430 (MH), 447 (MNH4), 452 (N4Na), 428 (MH); 1322 1H NMR (300 MHz, DMSO-d6) 9.84 (br, 0.5H), 9.40 (br, 0.5H), 8.12 (s, 0.5H), 8.02-7.91 (m, 4H), 7.75 (s, 0.5H), 7.38-7.29 (m, 4H), 5.09-4.94 (m, 1H), 4.61-4.52 (m, 0.5H), 4.06-3.95 (m, 0.5H), 3.67-3.34 (m, 4H), 3.24 (s, 3H).

EXAMPLE 155

()-N-1-methyl-3-(4-chloro 1,1-biphenyl-4-yl)-3-oxopropyl-N-hydroxyformamide

EXAMPLE 155A

(E)-1-(4-chloro1,1-biphenyl-4-yl)but-2-en-1-one 1323 A solution of 4-chlorodiphenyl (3.94 g, 0.02mol) and crotonyl chloride (2 mL, 0.02 mol) in CH2Cl2 (50 mL) was treated with AlC13 (2.78 g, 0.02 mol) at rt, stirred overnight, quenched with H2O, extracted with CH2Cl2, washed with brine, dried over MgSO4, filtered, and concentrated. Purification on silica gel with 5% CH2Cl2/hexanes provided 2.6 g (51%) of the desired compound.

EXAMPLE 155B

()-3-(hydroxyamino)-1-(4-chloro1,1-biphenyl-4-yl)-1-butanone 1324 A solution of Example 155A (0.1 g, 0.39 mmol), N H2OH.HCl (0.13 g, 1.95 mmol), and K2CO3 (0.27 g, 1.95 mmol) in THF (50 mL) was refluxed for 5h, quenched with H2O, extracted with ethyl acetate, dried over MgSO4, filtered, and concentrated. Purification on silica gel with 1% methanol/CH2Cl2 provided 0.009 g (8%) of the desired compound.

EXAMPLE 155C

()-N-1-methyl-3-(4-chloro1,1-biphenyl-4-yl)-3-oxopropyl-N-hydroxyformamide 1325 Example 155C was formylated according to the procedure of Example 1E to give the title compound. 1326 MS (ESI) 318 (MH), 335 (MNH4), 340 (MCl), 316 (MH); 1327 1H NMR (300 MHz, DMSO-d6-) 9.80 (s, 0.5H), 9.32 (s, 0.5H), 8.20 (s, 0.5H), 8.04 (d, 2H, J8.2 Hz), 7.82 (dd, 4H, J14.9, 8.4 Hz), 7.57 (d, 2H, J8.5 Hz), 4.91-4.79 (m, 0.5H), 4.50-4.36 (m, 0.5H), 3.54 (dd, 1H, J17.6, 8.1 Hz), 3.10 (dd, 1H, J17.0, 4.1 Hz), 1.26 (d, 1.5H, J6.7 Hz), 1.18 (d, 1.5H, J6.5 Hz); 1328 Anal. calcd for C17H16NO3Cl.0.25 H2O: C, 63.35; H, 5.16; N, 4.34. Found: C, 63.01; H, 5.42; N, 4.08.

EXAMPLE 156

()-N-F 1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-butylphenoxy)phenylsulfonylethyl-N-hydroxyformamide 1329 The title compound was prepared according to the procedures of Example 61, except substituting 4-(4-n-butylphenoxy)benzenethiol in place of 4-thiol-4-biphenyl-carbonitrile in Example 61A. 1330 MS (ESI) 532 (MH), 549 (MNH4), 554 (MNa), 530 (MH); 1331 1H NMR (300 MHz, DMSO-d6) 9.69 (s, 0.5H), 9.52 (s, 0.5H), 8.09 (s, 0.5H), 7.87 (dd, 2H, J8.8, 3.0 Hz), 7.68 (s, 0.5H), 7.28 (d, 2H, J8.5 Hz), 7.14-7.04 (m, 4H), 4.90-4.78 (m, 0.5H), 4.51-4.40 (m, 0.5H), 3.74-3.40 (m, 4H), 2.76 (s, 0.5H), 2.76 (s, 1.5H), 2.61 (t, 2H, J7.5 Hz), 1.63-1.52 (m, 2H), 1.39-1.26 (m, 2H), 1.26-1.22 (m, 6H), 0.91 (t, 3H, J7.2 Hz); 1332 Anal. calcd for C26H33N3O7S: C, 58.74; H, 6.25; N, 7.90. Found: C, 58.50; H, 6.43; N, 7.76.

EXAMPLE 157

()-N-3-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)-1-4-4-(trifluoromethyl)phenoxyphenylsulfonylmethylpropyl-N-hydroxyformamide 1333 The title compound was prepared according to the procedures of Example 61, except substituting 4-(4-trifluoromethylphenoxy)-benzenethiol in place of 4-thiol-4-biphenylcarbonitrile and Example 47A in place of Example 16B. 1334 MS (ESI) 544 (MH), 566 (MNa), 542 (MH); 1335 1H NMR (300 MHz, DMSO-d6) 9.97 (s, 0.5H), 9.60 (s, 0.5H), 8.32 (s, 0.5H), 8.23 (s, 0.5H), 8.11 (s, 0.5H), 7.95-7.89 (m, 2H), 7.82 (d, 2H, J8.8 Hz), 7.76 (s, 0.5H), 7.35-7.28 (m, 4H), 4.54-4.42 (m, 0.5H), 4.06-3.95 (m, 0.5H), 3.68-3.22 (m, 4H), 2.04-1.62 (m, 2H), 1.26 (s, 3H), 1.23 (s, 3H).

EXAMPLE 158

()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1336 The title compound was prepared according to the procedures of Example 61, except substituting 4-(4-trifluoromethoxyphenoxy)-benzenethiol in place of 4-thiol-4-biphenylcarbonitrile and Example 26A in place of Example 16b. 1337 MS (ESI) 546 (MH), 568 (MNa), 544 (MH); 1338 1H NMR (300 MHz, DMSO-d6) 9.64 (s, 0.5H), 9.45 (s, 0.5H), 8.35 (d, 1H, J12.2 Hz), 8.10 (s, 0.5H), 7.91 (dd, 2H, J8.9, 2.8 Hz), 7.68 (s, 0.5H), 7.47 (d, 2H, J9.2 Hz), 7.30-7.21 (m, 4H), 4.88-4.77 (m, 0.5H), 4.51-4.40 (m, 0.5H), 3.73-3.38 (m, 4H), 1.24 (s, 3H), 1.22 (s, 3H); 1339 Anal. calcd for C22H22N3O8SF3: C, 48.44; H, 4.06; N, 7.70. Found: C, 48.34; H, 4.29; N, 7.54.

EXAMPLE 159

()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-3-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methylpropyl-N-hydroxyformamide 1340 The title compound was prepared according to the procedures of Example 61, except substituting 4-(4-chlorophenoxy)-benzenethiol in place of 4-thiol-4-biphenylcarbonitrile and 1-bromo-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butan-2-one in place of Example 16b. 1341 MS (ESI) 524 (MH), 541 (MNH4), 546 (MNa), 522 (MH); 1342 1H NMR (300 MHz, DMSO-d6) 9.97 (s, 0.5H), 9.60 (s, 0.5H), 8.10 (s, 0.5H), 7.89-7.84 (m, 2H), 7.76 (s, 0.5H), 7.53 (d, 2H, J8.9 Hz), 7.25-7.16 (m, 4H), 4.50-4.38 (m, 0.5H), 4.04-3.92 (m, 0.5H), 3.64-3.24 (m, 4H), 2.79 (s, 1.5H), 2.75 (s, 1.5H), 2.02-1.86 (m, 1H), 1.74-1.61 (m, 1H), 1.27 (s, 3H), 1.24 (s, 3H); 1343 Anal. calcd for C23H26N3O7SCl.0.5 H2O: C, 51.83; H, 5.10; N, 7.88. Found: C, 51.84; H, 4.95; N, 7.92.

EXAMPLE 160

()-N-2-4-(4-cyano1,1-biphenyl-4-yl)oxycyclohexyl-N-hydroxyformamide 1344 The title compound was prepared from 2-chlorocyclohexanone first by alkylating with 4hydroxy-4-biphenylcarbonitrile as descibed in Example 16C, then converting the resulting ketone to the title compound through the oxime formation, reduction and formylation procedures described in examples 2D, 2E and 2F. 1345 MS(ESI): 337(MH), 354(M18), 359(M23), 673(2MH), 695(2M23); 1346 1H NMR (300 MHz, DMSO-d6): 9.90(s, 0.2H), 9.69(s, 0.3H), 9.48(s, 0.5H), 8.27(s, 0.2H), 8.05 (s, 0.3H), 8.01(s, 0.5H), 7.93-7.78(m, 4H), 7.67(m, 2H), 7.06(m, 2H), 4.55-4.17(m, 1H), 3.80-3.68(m, 1H), 2.30-2.00(m, 1H), 1.88-1.22(m, 7H).

EXAMPLE 161

()-N-2-4-4-(trifluoromethoxy)1,1-biphenyl-4-yl)oxy cyclohexyl-N-hydroxyformamide

EXAMPLE 161A 1347 To a solution of 100 mg (0.434 mmol) of (1S*,2S*)-2-((tert-butyldimethyl)silyl)oxy)-cyclohexanol, 132mg (0.521 mmol) of 4-(p-trifluoromethoxyphenyl)phenol and 342 mg (1.302 mmol) of triphenylphosphine in 5 ml THF under nitrogen at room temperature was added 171 ml (1.085 mmol) diethyl azodicarboxylate (DEAD). The resulting mixture was stirred at room temperature for 18h and then under reflux for 2 days. The solvent was removed under reduced pressure and the residue was chromatographed on silica gel with hexanes/ethyl acetate (24:1) to give 55 mg (27%) of the title compound as colorless oil. 1348 MS(ESI): 467(MH), 484 (MNH4).

EXAMPLE 161B

()-N-2-4-4-(trifluoromethoxy)1,1-biphenyl-4-yl)oxycyclohexyl-N-hydroxyformamide 1349 The title compound was prepared from Example 161 A, by first deprotecting the silyl ether as in Example 4D, then applying the sequence of reactions described in Examples 1C, 1D and 1E. 1350 MS(ESI): 396 (MH), 413 (M18), 418 (M23), 813 (2M23); 1351 1H NMR (CD3OD): 8 8.29 (s, 0.3H), 8.05 (s, 0.7H), 7.63 (d, J7.5 Hz, 2H), 7.52 (d, J7.5 Hz, 2H), 7.29 (d, J7.5 Hz, 2H), 7.02 (d, J7.5 Hz, 2H), 4.55-4.30 (m, 1.3H), 3.72 (m, 0.7H), 2.38-2.28 (m, 1H), 2.00-1.72 (m, 3H), 1.52-1.20 (m, 4H).

EXAMPLE 162

()-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3-methyl-6-oxo-1 (6H)-pyridazinyl)ethyl-N-hydroxyformamide

EXAMPLE 162A

()-1-3-4-(4-chlorophenoxy)phenylthio-2-hydroxypropyl-3-methyl-1H-pyridazin-6-one 1352 The title compound was prepared following the procedures of Example 1A and 1B, except substituting 6-methyl-3-2H-pyridazinone for phenol in Example 1A and 4-(4-chlorophenoxy)benzene thiol for 4-hydroxy-4-biphenylcarbonitrile in Example 1B.

EXAMPLE 162B

()-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3-methyl-6-oxo-1 (6H)-pyridazinyl)ethyl-N-hydroxyformamide 1353 Example 162A was converted to the title compound follwing the procedures described in Examples 2C-2F (inclusive) and 46D. 1354 MS (ESI) m/z 478 (MH); 1355 1H NMR (300 MHz, DMSO-d6) 9.79 (br, 0.5H), 9.52 (br, 0.5H); 8.04 (s, 0.5H), 7.89-7.84 (m, 2H), 7.66 (s, 0.5H), 7.55-7.52 (m, 2H), 7.32 (d, 1H), 7.23-7.16 (m, 4H), 6.86 (d, 1H), 5.04-4.95 (m, 0.5H), 4.58-4.49 (m, 0.5H), 4.26-4.18 (m, 1H), 4.12-4.05 (m, 1H), 3.79-3.66 (m, 1H), 3.56-3.51 (m, 1H), 2.22-2.20 (m, 3H); 1356 Anal. calcd for C21H20ClN3O6S: C, 52.78; H, 4.22; N, 8.79. Found: C, 52.71; H, 4.45; N, 8.49.

EXAMPLE 163

()-N-hydroxy-1-(6-oxo-1(6H)-pyridazinyl)methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyethyformamide 1357 The title compound was prepared following the procedures of Example 134 except subtituting 3-2H-pyridazinone for 5,5-dimethyloxazolidin-2,4-dione. 1358 MS (ESI) m/z 450 (MH); 1359 1H NMR (300 MHz, DMSO-d6) 9.97 (br, 0.5H), 9.61 (br, 0.5H), 8.28 (s, 0.5H), 7.96-7.92 (m, 1H), 7.87 (s, 0.5H), 7.76-7.72 (m, 2H), 7.65-7.61 (m, 2H), 7.46-7.40 (m, 3H), 7.04-6.94 (m, 3H), 5.09-5.00 (m, 0.5H), 4.59-4.50 (m, 0.5H), 4.46-4.11 (m, 4H); 1360 Anal. calcd for C21H18F3N3O6: C, 56.13; H, 4.04; N, 9.35. Found: C, 56.23; H, 3.79; N, 9.36.

EXAMPLE 164

()-N-1-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1361 The title compound was prepared following the procedures of Example 162 except substituting 1-methyluracil for 6-methyl-3-2H-pyridazinone and 4-(4-trifluoromethoxyphenoxy)benzene thiol for 4-(4-chlorophenoxy)benzene thiol. 1362 MS (ESI) m/z 544 (MH); 1363 1H NMR (300 MHz, DMSO-d6) 9.52 (br, 0.5H), 9.42 (br, 0.5H), 8.04 (s, 0.5H), 7.89-7.85 (m, 2H), 7.73 (s, 0.5H), 7.70-7.66 (m, 1H), 7.49-7.46 (m, 2H), 7.31-7.26 (m, 2H), 7.22-7.18 (m, 2H), 5.64 (d, 1H), 4.99-4.90 (m, 0.5H), 4.43-4.34 (m, 0.5H), 4.03-3.87 (m, 2H), 3.75-3.63 (m, 1H), 3.52-3.41 (m, 1H), 3.17 (s, 3H); 1364 Anal. calcd for C22H20F3N3O8S: C, 48.62; H, 3.71; N, 7.73. Found: C, 48.84; H, 3.99; N, 7.55.

EXAMPLE 165

()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-bromophenoxy) phenylsulfonylethyl-N-hydroxyformamide 1365 The title compound was prepared following the procedures of Example 61, except substituting 4-(4-bromophenoxy)benzene thiol in place of 4-thiol-4-biphenylcarbonitrile. 1366 MS (ESI) m/z 573 (MH); 1367 1H NMR (300 MHz, DMSO-d6) 9.70 (br, 0.5H), 9.51 (br, 0.5H), 8.09 (s, 0.5H), 7.91-7.88 (m, 2H), 7.68 (s, 0.5H), 7.66-7.62 (m, 2H), 7.22-7.19 (m, 2H), 7.16-7.12 (m, 2H), 4.88 (m, 0.5H), 4.49-4.42 (m, 0.5H), 3.71-3.42 (m, 4H), 2.77 (s, 1.5H), 2.76 (s, 1.5H), 1.25-1.23 (m, 6H); 1368 Anal. calcd for C22H24brN3O7S: C, 47.66; H, 4.36; N, 7.58. Found: C, 48.21; H, 4.79; N, 7.23.

EXAMPLE 166

()-N-1-(2,5-dioxo-4,4-dimethyl-1-imidazolidinyl)methyl-2-methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxypropyl-N-hydroxyformamide

EXAMPLE 166A

3-bromo-3-methyl-2-butanone 1369 A solution of 3-methyl-2-butanone (5 mL, 4.67 mol) in 70 mL of THF at 0 C. was treated with phenyltirmethylammonium tribromide, stirred 30 min at 0 C., quenched with NaHCO3, filtered, and concentrated to provide 7.5 g (97%) of the title compound. 1370 1H NMR (300 MHz, CDCl3) 2.45 (s, 3H), 1.87 (s, 6H).

EXAMPLE 166B

3-methyl-3-4-(trifluoromethoxy)1,1-biphenyl-4-yloxy-2-butanone 1371 A soln of 4-(4-trifluoromethoxyphenyl)phenol (6 g, 23.6 mmol) in 23 mL of DMF was treated with potassium carbonate (4 g) and Example 166A (5 g), stirred at rt for 16 h, filtered, and concentrated to provide 4.4 g (55%) of the title compound. 1372 MS (ESI) m/z 356 (M18).

EXAMPLE 166C

1-bromo-3-methyl-3-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyl-2-butanone 1373 A soln of Example 166B (4.4 g, 13.2 mmol) in 40 mL of CHCl3 at 0 C. was treated with bromine (1 mL), stirred at rt for 30 min, quenched with 2:1 satd NaUCO3/10% NaHSO3, extracted with ethyl acetate (250 mL), washed with brine, dried over Na2SO4, filtered, and concentrated to provide 5.5 g (100%) of the title compound. 1374 MS (ESI) m/z (M18).

EXAMPLE 166D

()-1-(2,5-dioxo-4,4-dimethyl-1-imidazolidinyl)-3-methyl-3-4-(trifluoromethoxy)1,1-biphenyl-4-yloxy-2-butanone 1375 A soln of Example 166C (5.5 g, 13.2 mmol) in 26 mL of DMF was treated with 5,5-dimethylhydantoin (1.69 g) and potassium carbonate (1.82 g), stirred at rt for 16 h, diluted wtih 150 mL of CHCl3, filtered, and concentrated. Purification on silica gel with 1:1 hexanes/ethyl acetate provided 4.05 g (66%) of the title compound. 1376 MS (ESI) m/z 463 (M1).

EXAMPLE 166E

()-N-1-(2,5-dioxo-4,4-dimethyl-1-imidazolidinyl)-2-methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxyhydroxylamine 1377 A soln of Example 166D (550 mg, 1.18 mmol) in 6 mL of 1:1 THF/ethanol was treated with hydroxylamine.HCl (99 mg) and pyridine (115 L), heated at 75-80 C. for 8 h, cooled to 0 C., treated with borane-pyridine (359 L) and HCl (1.78 mL, 4N in dioxane), stirred 16 h at rt, quenched with satd NaHCO3, extracted with ethyl acetate (320 mL), washed with brine, dried over Na2SO4, filtered, and concentrated. Purification on silica gel with 1:2 hexanes/ethyl acetate provided 230 mg (40%) of the title compound. 1378 MS (ESI) m/z 482 (MH).

EXAMPLE 166F

()-N-1-(2,5-dioxo-4,4-dimethyl-1-imidazolidinyl)methyl-2-methyl-2-4-(trifluoromethoxy)1,1-biphenyl-4-yloxypropyl-N-hydroxyformamide 1379 Example 166E was converted to the title compound following the formylation procedure described in Example 1E. 1380 MS (ESI) m/z 510 (M1); 1381 1H NMR (300 MHz, DMSO-d6) 9.56 (br, 0.5H), 9.39 (br, 0.5H), 8.40 (br, 0.5H), 8.38 (br, 1H), 8.32 (s, 0.5H), 7.94 (s, 0.5H), 7.80-7.76 (m, 2H), 7.65-7.60 (m, 2H), 7.45-7.42 (m, 2H), 7.24-7.16 (m, 2H), 4.70 (dd, 0.5H), 4.26 (dd, 0.5H), 4.12-3.98 (m, 1H), 3.91-3.79 (m, 1H), 1.38-1.25 (m, 12H).

EXAMPLE 167

()-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)ethyl-N-hydroxyformamide 1382 The title compound was prepared following the procedures of Example 162 except substituting 1-methyluracil for 6-methyl-3-2H-pyridazinone. 1383 MS (ESI) m/z 511 (M18); 1384 1H NMR (300 MHz, DMSO-d6) 9.52 (br, 0.5H), 9.43 (br, 0.5H), 8.04 (s, 0.5H), 7.87-7.83 (m, 2H), 7.73 (s, 0.5H), 7.70 (d, 0.5H), 7.66 (d, 0.5H), 7.55-7.50 (m, 2H), 7.22-7.15 (m, 4H), 5.64 (d, 1H), 4.99-4.90 (m, 0.5H), 4.42-4.34 (m, 0.5H), 4.04-3.86 (m, 2H), 3.74-3.62 (m, 1H), 3.52-3.40 (m, 1H), 3.26 (s, 3H); 1385 Anal. calcd for C21H20ClN3O7S: C, 51.07; H, 4.08; N, 8.51. Found: C, 51.35; H, 4.29; N, 8.40.

EXAMPLE 168

()-N-hydroxy-N-1-(3-methyl-6-oxo-1(6H)-pyridazinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1386 The title compound was prepared following the procedures of Example 162 except subtituting 4-(4-trifluoromethoxyphenoxy)benzene thiol for 4-(4-chlorophenoxy)benzene thiol. 1387 MS (ESI) m/z 528 (MH); 1388 1H NMR (300 MHz, DMSO-d6) 9.78 (br, 0.5H), 9.50 (br, 0.5H), 8.03 (s, 0.5H), 7.91-7.86 (m, 2H), 7.65 (s, 0.5H), 7.49 (d, 2H), 7.34-7.26 (m, 3H), 7.22-7.18 (m, 2H), 6.86 (d, 1H), 5.06 (m, 0.5H), 4.60-4.48 (m, 0.5H), 4.27-4.18 (m, 1H), 4.13-4.06 (m, 1H), 3.80-3.66 (m, 1H), 3.59-3.49 (m, 1H), 2.22 (d, 3H); 1389 Anal. calcd for C22H20F3N3O7S: C, 50.10; H, 3.82; N, 7.97. Found: C, 50.21; H, 3.97; N, 7.96.

EXAMPLE 169

()-N-hydroxy-N-1-(1-methyl-1H-indol-4-yl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1390 The title compound was prepared according to the procedures of Example 126, except substituting methyl 1-methyl-4-indolecarboxylate for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenyl)-phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1391 MS (ESI) 533 (MH); 1392 1H NMR (300 MHz, DMSO-d6) 9.95 (s, 0.5H), 9.56 (s, 0.5H), 8.13 (s, 0.5H), 7.90-7.85 (d, 2H, J8.9 Hz), 7.50-7.40 (m, 4H), 7.2-7.0 (m, 6H), 6.53 (s, 1H), 6.1 (s, 0.5H), 5.70 (s, 0.5H), 4.15 (m, 2H), 3.7-3.65 (m, 4H); 1393 Anal. calcd for C25H21N206SF3: C, 56.17; H, 3.96; N, 5.24. Found: C, 56.33; H, 4.38; N, 4.78.

EXAMPLE 170

()-N-hydroxy-N-1-(1-methyl-1H-indol-2-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1394 The title compound was prepared according to the procedures of Example 126, except substituting methyl 1-methyl-2-indolecarboxylate for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenyl) phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1395 MS (ESI) 533 (MH); 1396 1H NMR (300 MHz, DMSO-d6) 9.9 (s, 0.5H), 9.6 (s, 0.5H), 7.9-7.85 (d, 2H, J8.8 Hz), 7.52-7.48 (d, 2H, J8.8 Hz), 7.4-7.35 (m, 2H), 7.25-7.20 (d, 2H, J8.67 Hz), 7.15-7.00 (m, 4H), 6.40 (s, 0.5H), 6.1 (s, 0.5H), 4.2 (s, 1H), 4.05-3.90 (m, 2H), 3.75 (s, 3H); 1397 Anal. calcd for C25H21N2O6SF3.0.25 ethyl acetate: C, 56.11; H, 4.16; N, 5.03. Found: C, 56.62; H, 4.49; N, 4.80.

EXAMPLE 171

()-N-1-(4-chlorophenyl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1398 The title compound was prepared according to the procedures of Example 75, except substituting 4-chlorobenzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1399 MS (ESI) 548 (MH); 1400 1H NMR (300 MHz, DMSO-d6) 10.25 (s, 0.5H), 9.70 (s, 0.5H), 8.25-8.1 (m, 1H), 7.90-7.85 (d, 2H, J8.6 Hz), 7.77-7.7.70 (d, 2H, J8.8 Hz), 7.65 (s, 1H), 7.52-7.46 (d, 2H, J8.7 Hz), 7.23-7.10 (d, 2H, J8 Hz), 5.87 (s, 0,5H), 5.55 (s, 0.5H), 4.20-4.00 (m, 3H); 1401 Anal. calcd for C23H17NO6SF6.1.25 ethyl acetate: C, 48.29; H, 3.43; N, 2.44. Found: C, 48.01; H, 3.00; N. 2.00.

EXAMPLE 172

()-N-hydroxy-N-2-4-(trifluoromethoxy)phenoxyphenylsulfonyl-1-4-(trifluoromethyl)phenylethylformamide 1402 The title compound was prepared according to the procedures of Example 75, except substituting 4-trifluoromethylbenzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in Example 75A. 1403 MS (ESI) 514 (MH), 516 (MH); 1404 1H NMR (300 MHz, DMSO-d6) 10.01 (s, 0.5H), 9.65 (s, 0.5H), 8.25-8.15 (m, 1H), 7.90-7.80 (d, 2H, J8.9 Hz), 7.55-7.49 (d, 8.7H), 7.4 (m, 3H), 7.34-7.25 (m, 3H), 7.20-7.15 (d, 2H, J8.9 Hz), 5.7 (s, 0.5H), 5/48 (s, 0.5H), 4.25-4.0 (m, 3H); 1405 Anal. calcd for C22H17NO6SF3Cl: C, 51.22; H, 3.32; N, 2.71. Found: C, 51.30; H, 3.35; N, 2.53.

EXAMPLE 173

()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1406 The title compound was prepared following the procedures of Example 162, except using hydantoin on place of 6-methyl-3-2H-pyridazinone and 4-(4-trifluoromethoxyphenyl)benzenethiol in place of 4-(4-chlorophenyl)benzenethiol. 1407 MS (ESI) 518 (MH), 535 (MNH4), 540 (MNa), 516 (MH); 1408 1H NMR (300 MHz, DMSO-d6) 9.79 (s, 0.5H), 9.53 (s, 0.5H), 8.15 (d, 1H, J6.6 Hz), 8.10 (s, 0.5H), 7.93-7.88 (m, 2H), 7.73 (s, 0.5H), 7.48 (d, 2H, J9.2 Hz), 7.32-7.20 (m, 4H), 4.88-4.77 (m, 0.5H), 4.48-4.34 (m, 0.5H), 3.94-3.40 (m, 6H).

EXAMPLE 174

()-N-hydroxy-N-1-(2-thienylthio)methyl-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide

EXAMPLE 174A

methyl 2-(2-thienylthio)acetate 1409 To a solution of thiophene-2-thiol (1.2 g, 10.3 mmol) in anhydrous DMF (30 mL) was added cesium carbonate (3.9 g, 12 mmol) and the resulting suspension was stirred for 15 min at ambient temperature, then treated with methyl bromoacetate (1.53 g, 10 mmol). The purple suspension was stirred for 1 h, then poured into water (30 mL) and extracted twice with 300 mL EtOAc. The combined organic extracts were washed with brine, dried, filtered, concentrated and the residue was purified via column chromatography eluting with 10% EtOAc/Hexanes to give 1.48 g (79%) of the title compound.

EXAMPLE 174B

()-N-hydroxy-N-1-(2-thienylthio)methyl-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1410 The title compound was prepared according to the procedures of Example 126, except substituting Example 174A for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1411 mp 120-122 C.; 1412 MS (ESI()) 533 (MNH4H2O), 550 (MNH4), 555 (MNa); 1413 1H NMR (300 MHz, DMSO-d6): 10.12 (bs, 1/2H), 9.80 (bs, 1/2H), 8.35 (s, 1/2H), 7.89-7.98 (m, 2.5H), 7.73-7.79 (m, 1H), 7.55-7.63 (m, 2H), 7.34-7.42 (m, 2H), 7.23-7.32 (m, 3H), 7.11-7.20 (m, 1H), 4.72-4.82 (m, 1/2H), 4.04-4.13 (m, 1/2H), 3.63-3.88 (m, 2H), 2.99-3.19 (m, 2H); 1414 Anal. calcd for C21H18F3NO6S3: C, 47.27; H, 3.40; N, 2.62;S, 18.02, F, 10.68. Found: C, 47.05; H, 3.43; N, 2.82; S, 17.83, F, 10.37.

EXAMPLE 175

()-N-hydroxy-N-1-(4-methylphenyl)sulfonylmethylaminomethyl-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide

EXAMPLE 175A

ethyl 2-methyl(4-methylphenyl)sulfonylaminoacetate 1415 An ice cold suspension of sarcosine ethyl ester hydrochloride salt (3.1 g, 20 mmol) in CH2Cl2 (150 mL) was sequentially treated with triethyl amine (4.45 g, 44 mmol) and tosyl chloride (4.19 g, 22 mmol) and stirred for 1 h, after which time the ice bath was removed, and the reaction was allowed to stir for an additional 1 h. The reaction mixture was then partitioned between water and CH2Cl2 and the organic extract was washed with brine, dried, filtered, and concentrated to give 5.7 g of the title compound as a white solid.

EXAMPLE 175B

()-N-hydroxy-N-1-(4-methylphenyl)sulfonylmethylaminomethyl-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1416 The title compound was prepared according to the procedures of Example 126, except substituting Example 175A for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1417 mp 160.7-162.5 C.; 1418 1H NMR (300 MHz, DMSO-d6): 9.97 (bs, 1/2H), 9.72 (bs, 1/2H), 8.18 (s, 1/2H), 7.88-7.98 (m, 2H), 7.82 (s, 1/2H), 7.59-7.68 (m, 2H), 7.37-7.50 (m, 4H), 7.20-7.32 (m, 4H), 4.76-4.85 (m, 1/2H), 4.25-4.36 (m, 1/2H), 3.62 (dd, 1H, J14, 8 Hz), 3.44-3.56 (m, 1H), 3.25 (dd, 1/2H, J8, 14 Hz), 3.07 (d, 1/2H, J8 Hz), 2.90 (dd, 1/2H, J14, 8 Hz), 2.59-2.66 (m, 1.5H), 2.54-2.59 (m, 1H), 2.48-2.54 (m, 1H), 2.40 (s, 3H); 1419 MS (ESI()) 600.8 (MH), 636.9 (MCl), 1203.4 (2MH); 1420 Anal. calcd for C25H25F3N2O8S2: C, 49.82; H, 4.18; N, 4.65;S, 10.64; F, 9.46. Found: C, 49.67; H, 4.19; N, 4.50;S, 10.59; F, 9.38.

EXAMPLE 176

()-N-hydroxy-N-2-(methoxyethoxy)methyl-1-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1421 The title compound was prepared according to the procedures of Example 126, except substituting ethyl (2-methoxy)ethoxyacetate for methyl methoxyacetate and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1422 MS (ESI) 492 (MH); 1423 1H NMR (DMSO-d6) 3.22 (s, 3H), 3.42-3.66 (m, 8H), 4.14-4.25 (m, 0.5H), 4.68-4.79 (m, 0.5H), 7.23 (d, 2H, J9 Hz), 7.28 (d, 2H, J9 Hz), 7.48 (d, 2H, J9 Hz), 7.83 (s, 0.5H), 7.93 (d, 2H, J9 Hz), 8.14 (s, 0.5H), 9.55 (bs, 0.5H), 9.96 (bs, 0.5H); 1424 Anal. calcd for C20H22NO8SF3: C, 48.68; H, 4.49; N, 2.83. Found: C, 48.61; H, 4.60; N, 2.80.

EXAMPLE 177

()-N-1-(1,6-dihydro-3-methyl-2,6-dioxo-1(6H)-pyrimidinyl)methyl-2-(4-phenoxyphenylsulfonylethyl-N-hydroxyformamide 1425 The title compound was prepared following the procedures of Example 162, except using 4-(phenoxy)-benzenethiol in place of 4-(4-chlorophenoxy)-benzenethiol. 1426 MS (ESI) m/z 460 (MH); 1427 1H NMR (300 MHz, DMSO-d6) 9.55 (br, 0.5H), 9.47 (br, 0.5H), 8.05 (s, 0.5H), 7.86-7.83 (m, 2H), 7.74 (s, 0.5H), 7.71-7.67 (m, 2H), 7.52-7.47 (m, 2H), 7.30-7.25 (m, 2H), 7.19-7.11 (m, 4H), 5.64 (d, 1H), 4.99-4.91 (m, 0.5H), 4.42-4.34 (m, 0.5H), 4.05-3.85 (m, 2H), 3.73-3.62 (m, 1H), 3.51-3.39 (m, 1H), 3.27 (s, 3H); 1428 Anal. calcd for C21H21N3O7S: C, 54.90; H, 4.61; N, 9.15. Found: C, 55.01; H, 4.91; N, 8.90.

EXAMPLE 178

()-N-hydroxy-N-1-(4-hydroxyphenyl)-2-4-(trifluoromethyl)1,1-biphenyl-4-ylsulfonylethylformamide 1429 A suspension of Example 129 (186 mg, 0.366 mmol) in dichloromethane (20 mL) at 78 C. was treated with boranetrifluoride diethyl etherate (55.6 mL, 0.439 mmol), stirred at 0 C. for 3 hours and left at room temperature overnight, treated with water, extracted with ethyl acetate, dried (Na2SO4), filtered, concentrated and purified on silica gel with 80% ethyl acetate/hexanes to provide 45 mg (26%) of the title compound as an orange solid. 1430 mp 225 C. decomposed; 1431 MS (ESI) m/z 466 (MH), 483 (MNH4), 464 (MH), 488 (MNa); 1432 1H NMR (300 MHz, DMSO-d6) 3.90-4.22 (br, 2H), 5.32 (br, 0.5H), 5.66 (br, 0.5H), 6.61-6.64 (d, 2H, J9 Hz), 7.00-7.20 (2H), 7.84-8.23 (m, 1OH), 9.50 (s, 1H); 1433 Anal. calcd for C22H18NF3O5S 0.25 H2O: C, 56.22; H, 3.96; N, 2.98. Found: C, 56.09; H, 4.00; N, 2.83.

EXAMPLE 179

()-N-hydroxy-N-1-(2,2-dimethyl-1,3-dioxan-5-yl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide

EXAMPLE 179A

()-N-1-(2,2-dimethyl-1,3-dioxan-5-yl)-2-4 (trifluoromethoxy)phenoxyphenylsulfonylethylhydroxylamine 1434 The title compound was prepared according to the procedures of Example 126A, 126B, 75C except substituting 2,2-dimethyl-5-ethylcarboxylate-1,3-dioxane (Tetrahedron 1991, 47, 1001) for methyl methoxyacetate and 4-(4-trifluoromethoxyphenyl)-phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)-phenyl methyl sulfone.

EXAMPLE 179B

()-N-hydroxy-N-1-(2,2-dimethyl-1,3-dioxan-5-yl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1435 Example 179A was converted to the title compound following the fomylation procedure of Example 75D. 1436 mp 139.5-140.7 C.; 1437 MS (ESI) m/z 520 (MH), 542 (MNa), 518 (MH), 554 (MCl); 1438 1H NMR (300 MHz, DMSO-d6) 1.17-1.30 (6H), 3.36-3.77 (m, 5H), 3.79-3.92 (0.75H), 4.03 (0.25H), 4.15-4.24 (m, 0.75H), 6.57-4.68 (0.25H), 7.19-7.28 (m, 4H), 7.42-7.50 (d, 2H, J9 Hz), 7.76 (s, 0.75H), 7.88-7.96 (m, 2H), 8.12 (s, 0.25H), 9.71 (br, 0.75H); 1439 Anal. calcd for C22H24NF3O8S: C, 50.86; H, 4.65; N, 2.69. Found: C, 50.99; H, 4.97; N, 2.73.

EXAMPLE 180

()-N-hydroxy-N-3-hydroxy-2-(hydroxymethyl)-1-4-(trifluoromethoxy)phenoxyphenylsulfonylmethylpropylformamide 1440 Example 179A was converted to the title compound following the procedures of Example 141A and B. 1441 mp 129.2-131.3 C.; 1442 MS (ESI) m/z 480 (MH), 502 (MNa), 478 (MH); 1443 1H NMR (300 MHz, DMSO-d6) 1.69-1.79 (m, 1H), 3.57-3.80 (m, 2H), 3.24-3.51 (m, overlapped w/solventH), 4.13-4.19 (dt, 1H, J1.5, 8.4 Hz), 4.64-4.70 (1H), 7.19-7.30 (m, 4H), 7.45-7.48 (d, 2H, J9 Hz), 7.678 (s, 0.7H), 7.86-7.90 (m, 2H), 8.04 (s, 0.3H); 1444 Anal. calcd for C19H20NF3O8S.0.25 H2O: C, 47.15; H, 4.26; N, 2.89. Found: C, 47.29; H, 4.44; N, 2.56.

EXAMPLE 181

()-N-hydroxy-N-1-(hydroxymethyl)-2-(4-chlorophenyl)thiophenylsulfonylethylformamide 1445 The title compound was prepared according to the procedures of Example 125, except substituting tert-butyldimethylsilyloxy-acetaldehyde for 3-tert-butyldimethyl-silyloxypropionaldehyde and 4-(4-chlorophenylthio)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1446 mp 148.5-150.0 C.; 1447 MS (ESI) m/z 402 (MH), 424 (MNa), 400 (MH); 1448 1H NMR (300 MHz, DMSO-d6) 3.30-3.62 (m, overlaped w/solventH), 3.90-4.01 (m, 0.5H), 4.47-4.60 (m, 0.3H, J1.5), 5.01 (br, 0.7H), 7.36-7.39 (d, 2H, J9 Hz), 7.73-7.85 (m, 2.7H), 8.11 (s, 0.3H), 9.41 (brs, 0.7H), 9.83 (brs, 0.3H); 1449 Anal. calcd for C16H16NClO5S2: C, 47.81; H, 4.01; N, 3.48. Found: C, 47.55; H, 4.14; N, 3.28.

EXAMPLE 182

()-N-hydroxy-N-1-(4-morpholinylmethyl)-2-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1450 The title compound was prepared according to the procedures of Example 126, except substituting methyl morpholinoacetate for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1451 mp 160.9-162.7 C.; 1452 MS (ESI) m/z 505 (MH), 527 (MNa), 503 (MH), 539(MCl); 1453 1H NMR (300 MHz, DMSO-d6) 2.10-2.42 (m, 6H), 3.48-3.65 (m, 6H), 4.13 (br, 0.6H), 4.68 (br, 0.4H), 7.18-7.32 (m, 4H), 7.46-7.49 (d, 2H, J9 Hz),7.84-7.95 (2.6H), 8.14 (s, 0.4H), 9.46 (s, 0.6H), 9.88 (s, 0.4H); 1454 Anal. calcd for C21H23N2F3O7S: C, 49.99; H, 4.59; N, 5.55. Found: C, 49.77; H, 4.62; N, 5.39.

EXAMPLE 183

()-N-hydroxy-N-4-hydroxy-1-4-(trifluoromethoxy)phenoxyphenylsulfonylmethylbutylformamide 1455 The title compound was prepared according to the procedures of Example 125, except substituting 4-tert-butyldimethylsilyloxy-butanaldehyde for 3-tert-butyldimethylsilyloxy-propionaldehyde and 4-(4-trifluoromethoxyphenyl)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1456 mp 92.0-93.9 C.; 1457 MS (ESI) m/z 464 (MH), 486 (MNa), 462 (MH); 1458 1H NMR (300 MHz, DMSO-d6) 1.13-1.40 (m, 2H), 1.40-1.68 (m, 2H), 3.22-3.47 (m, overlaped w/solventH), 3.53-3.68 (m, 1H), 4.02-4.13 (m, 0.5H), 4.37-4.49 (m, 1H), 4.49-4.58 (m, 0.45H), 7.20-7.23 (d, 2H, J9 Hz), 7.25-7.32 (dd, 2H, J3, 9 Hz), 7.46-7.49 (d, 2H, J9 Hz), 7.81 (s, 0.6H), 7.88-7.91 (d, 2H, J9 Hz), 8.12 (s, 0.4H), 9.46 (s, 0.6H), 9.83 (s, 0.4H); 1459 Anal. calcd for Cl9H20NF3O7S: C, 49.24; H, 4.35; N, 3.02. Found: C, 49.22; H, 4.49; N, 2.95.

EXAMPLE 184

()-N-1-(1H-isoindole-1,3 (2B)-dione)methyl-2-4-(4-chlorophenoxy)phenylsulfonylethyl-N-hydroxyformamide

EXAMPLE 184A

2-(3-bromo-2-oxopropyl)-1H-isoindole-1,3(2H-dione 1460 The title compound was prepared following the procedures of examples 16A and 16B, except substituting phthalimide for 1,5,5-trimethylhydantoin in example 16A.

EXAMPLE 184B

()-N-1-(1H-isoindole-1,3(2H)-dione)methyl-2-4-(4-chlorophenoxy)phenylsulfonylethyl-N-hydroxyformamide 1461 Alkylation of example 184A with 4-(4-chlrophenoxy)benzene thiol as described in example 61 A followed by the synthetic transformations described in example 61B and 61 C gave the title compound. 1462 1H NMR (300 MHz, d6-DMSO) 9.96 (br, 0.5H), 9.67 (br, 0.5H), 8.06 (s, 0.5H), 7.91-7.84 (m, 6H), 7.75 (s, o0.5H), 7.55-7.51 (m, 2H), 7.22-7.13 (m, 4H), 5.01-4.91 (m, 0.5H), 4.56-4.46 (m, 0.5H), 3.89-3.62 (m, 4H); 1463 MS (ESI) m/e 532 (M18); 1464 Anal. calcd for C24H19ClN2O7S: C, 55.98; H, 3.72; N, 5.44. Found: C, 56.09; H, 3.71; N, 5.31.

EXAMPLE 185

()-N-1-(2,5-dioxo-3,4,4-trimethyl-1-imidazolidinyl)methyl-2-4-(4-cyanophenoxy)phenylsulfonylethyl-N-hydroxyformamide 1465 The title compound was prepared according to the procedures of example 61, except substituting 4-(4-cyanophenoxy)-benzene thiol for 4-thiol-4-biphenylcarbonitrile. 1466 1H NMR (300 MHz, d6-DMSO) 9.74 (br, 0.5H), 9.52 (br, 0.5H), 8.10 (s, 0.5H), 7.97-7.90 (m, 4H), 7.68 (s, 0.5H), 7.36-7.28 (m, 4H), 4.89-4.79 (m, 0.5H), 4.52-4.42 (m, 0.5H), 3.76-3.37 (m, 4H), 2.76 (s, 1.5H), 2.76 (s, 1.5H), 1.26-1.23 (m, 6H); 1467 MS (ESI) m/e 501 (MH); 1468 Anal. calcd for C23H24N4O7S: C, 55.19; H, 4.83; N, 11.19. Found: C, 55.39; H, 5.19; N, 10.96.

EXAMPLE 186

()-N-hydroxy-N-1-(2-pyridinyl)-2-4-(trifluoromethoxy)1,1-biphenyl-4-ylsulfonylethylformamide 1469 The title compound was prepared according to the procedures of example 75, except substituting 2-pyridine carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in example 75A. 1470 m.p.116.4-117.6 C.; 1471 1H NMR (300 MHz, DMSO-d6) 3.88-4.04 (m, 1H), 4.28-4.36 (dd, 1H, J4.5, 15 Hz), 5.50 (br, 0.5H), 5.84 (br, 0.5H), 7.12-7.44 (m, 6H), 7.44-7.50 (d, 2H, J9 Hz), 7.74-7.95 ( 2H), 8.18 (s, 0.5H), 8.25 (s, 0.5H), 8.47 (1H), 9.66 (s, 0.5H); 1472 MS (ESI) m/e 483 (MH), 505 (MNa), 481 (MH). 517 (MCl); 1473 Anal. calcd for C21H17N2F3O6S: C, 52.28; H, 3.55; N, 5.80. Found: C, 51.95; H, 3.24; N, 5.63.

EXAMPLE 187

()-N-1-(4-chlorophenoxy)phenylsulfonylmethyl-4-hydroxybutyl-N-hydroxyformamide 1474 The title compound was prepared according to the procedures of example 125, except substituting 4-tert-butuldimethylsilyloxy-butanaldehyde for 3-tert-butuldimethyl-silyloxypropionaldehyde and 4-(4-chloro-phenoxy)phenyl methyl sulfone for 4-(4- trifluoromethylphenyl)phenyl methyl sulfone 1475 m.p.126.9-128.8 C.; 1476 1H NMR (300 MHz, DMSO-d6) 1.20-1.38 (m, 2H), 1.41-1.65 (m, 2H), 3.35-3.44 (dd, 1H, J3, 12 Hz), 3.52-3.67 (m, 1H), 4.01-4.13 (br, 0.4H), 4.33-4.58 (0.6H), 7.15-7.23 (dd, 4H, J3, 9 Hz), 7.48-7.56 (d, 2H, J9 Hz), 7.81 (s, 0.6H), 7.85-7.92 (d, 2H, J9 Hz), 8.12 (s, 0.4H), 9.44 (br, 0.6H), 9.82 (br, 0.4H); 1477 MS (ESI) m/e 414 (MH), 431 (MNH4), 436 (MNa), 412 (MH); 1478 Anal. calcd for C18H20NClO6S: C, 52.23; H, 4.87; N, 3.38. Found: C, 52.21; H, 4.93; N, 3.21.

EXAMPLE 188

()-N-1-(4-trifluoromethoxyphenoxy)phenylsulfonylmethyl-3-hydroxypropyl-N-hydroxyformamide 1479 The title compound was prepared according to the procedures of example 125, except substituting 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1480 m.p. 119.5-122.6 C.; 1481 1H NMR (300 MHz, DMSO-d6) 1.52-1.80 (m, 2H), 3.18-3.31 (m, 1H), 3.47-3.50 (1H), 3.54-3.72 (m, 1H), 4.20-4.32 (m, 0.7H), 4.43-4.49 (t, 0.3H, J6 Hz), 4.55-4.61 (t, 0.7H, J6 Hz), 4.64-4.76 (m, 0.3H), 7.17-7.26 (d, 2H, J9 Hz), 7.26-7.32 (2H), 7.43-7.51 (d, 2H, J9 Hz), 7.74 (s, 0.7H), 7.86-7.93 (d, 2H, J9 Hz), 8.09 (s, 0.3H), 9.46 (s, 0.7H), 9.81 (s, 0.3H); 1482 MS (ESI) m/e 450 (MH), 467 (MNH4), 472 (MNa), 448 (MH); 1483 Anal. calcd for C18H18NF3O7S: C, 48.10; H, 4.03; N, 3.11. Found: C, 48.47; H, 4.10; N, 2.97.

EXAMPLE 189

()-N-hydroxy-N-1-(4-trifluoromethoxyphenoxy)methyl-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1484 The title compound was prepared according to the procedures of example 126, except substituting ethyl 4-trifluomethoxyphenoxy-acetate (prepared from ethyl bromoacetate and 4-trifluoromethoxy phenol as in example 174A) for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1485 1H NMR (DMSO-d6) 3.55-3.79 (m, 2H), 3.96-4.15 (m, 2H), 4.38-4.50 (m, 0.5H), 4.86-4.97 (m, 0.5H), 6.95 (dd, 2H, J3,9 Hz), 7.23 (d, 2H, J9 Hz), 7.24-7.35 (m, 4H), 7.47 (d, 2H, J9 Hz), 7.93 (d, 2H, J6 Hz), 7.96 (s, 0.5H), 8.18 (s, 0.5H), 9.68 (bs, 0.5H), 10.08 (bs, 0.5H); 1486 MS (ESI) 594 (MH); 1487 Anal. Calcd for: C24H19NO8SF6 C, 48.40; H, 3.21; N, 2.35. Found: C, 48.35; H, 3.42; N, 2.35.

EXAMPLE 190

S-(R*,R*)-N-hydroxy-N-1-(2,2-dimethyl-1,3-dioxol-4-yl)-2-4-(4-phenyl-1-piperidinyl)phenylsulfonylethylformamide 1488 The title compound was prepared following the procedures described in example 145 starting with 4-(4-phenylpiperidine)phenylmethyl sulfone (prepared by addition of 4-phenylpiperidine to (4-fluorophenyl)methyl sulfone) and commercially available methyl (R)-2,2-dimethyl-1,3-dioxolane-4-carboxylate. 1489 1H NMR (300 MHz, DMSO-d6) 1.15-1.35 (m, 6H), 1.6-1.9 (m, 4H), 2.7-3.3 (m, 4H), 3.5-3.6 (m, 2H), 3.9-4.2 (m, 4.5H), 4.5-4.6 (t, 0.5H, J5.6 Hz), 7.12 (d, 2H, J9.3 Hz), 7.15-7.35 (m, 5H), 7.6-7.7 (m, 2H), 7.82 (s, 0.5H), 8.18 (s, 0.5H), 9.65 (s, 0.5H), 10.00 (br s, 0.5H); 1490 MS (ESI) 489 (MH); 1491 Anal. Calcd for C25H32N2O6S: C, 61.45; H, 6.60; N, 5.73. Found: C, 61.54; H, 6.53; N, 5.57.

EXAMPLE 191

()-N-hydroxy-N-1-(4-trifluoromethoxyphenyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1492 The title compound was prepared according to the procedures of example 75, except substituting 4-trifluoromethoxy)benzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in example 75A. 1493 1H NMR (300 MHz, DMSO-d6) 4.0-4.2 (m, 4H), 5.45-5.55 (br m, 0.5H), 5.7-5.8 (br m, 0.5H), 7.14 (d, 2H, J8.1 Hz), 7.20-7.35 (m, 4H), 7.35-7.60 (m, 4H), 7.84 (d, 2H, J7.5 Hz), 8.1-8.3 (m, 1H), 9.66 (br s, 0.5H), 10.10 (br s, 0.5H); 1494 MS (ESI) 566 (MH), 588 (M23); 1495 Anal. Calcd for C23H17NO7SF6: C, 48.85; H, 3.03; N, 2.47. Found: C, 48.96; H, 3.17; N, 2.45.

EXAMPLE 192

S-(R*,R*,R*)-N-1-(2,2,5-trimethyl-1,3-dioxol-4-yl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethyl-N-hydroxyformamide 1496 The title compound was prepared following the procedures described in example 145 except substituting commercially available methyl 3,4-isopropylidene-L-threonate for methyl (S)-2,2-dimethyl-1,3-dioxolane-4-carboxylate. 1497 1H NMR (300 MHz, DMSO-d6) 1.2-1.3 (m, 9H), 3.3-3.5 (m, 2H), 3.6-3.9 (m, 3H), 4.1-4.2 (apparent t, 0.5H, J5.0 Hz), 4.6-4.7 (apparent t, 0.5H, J5.0 Hz), 7.2-7.3 (m, 4H), 7.48 (d, 2H, J9.0 Hz), 7.85-8.00 (m, 2.5H), 8.15 (s, 0.5H), 9.69 (s, 0.5H), 9.95 (s, 0.5H); 1498 MS (ESI) 520 (MH), 537 (M18); 1499 Anal. Calcd for C22H24NO8SF3: C, 50.86; H, 4.65; N, 2.69. Found: C, 51.01; H, 4.38; N, 2.47.

EXAMPLE 193

()-N-hydroxy-N-1-(2-trifluoromethylphenyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1500 The title compound was prepared according to the procedures of example 75, except substituting 2-trifluoromethylbenzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in example 75A. 1501 1H NMR (DMSO-d6) 9.8 (bs, 0.5H), 8.17 (s, 0.5H), 8.10 (s, 0.5H), 7.5-7.98 (mm, 8H), 7.15-7.35 (mm, 4H), 6.05-6.15 (m, 0.5H), 5.48-5.50 (m, 0.5H), 4.39-4.44 (m, 1.0H), 3.90-4.15 (m, 2H); 1502 MS (ESI) 550 (MH), 567 (MNH4), 548 (MH); 1503 Anal. Calcd for: C23H17NO6SF6.0.25EtOAc; C, 50.44; H, 3.35; N, 2.454. Found: C, 50.50; H, 3.48; N, 2.32.

EXAMPLE 194

()-N-hydroxy-N-1-(4-fluorophenyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1504 The title compound was prepared according to the procedures of example 75, except substituting 4-fluorobenzaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in example 75A. 1505 1H NMR (DMSO-d6) 9.65 (s, 0.5H), 8.11-8.20 (m, 1H), 7.81-7.89 (d, 2H, 7.9 Hz), 7.46-7.51 (d, 8.OH), 7.40-7.50 (m, 1H), 7.24-7.30 (d, 2H, 7.8 Hz), 7.11-7.19 (d, 4H, J8.0 Hz), 5.70-5.73 (bs, 0.5H), 5.48-5.51 (bs, 0.5H), 3.98-4.10 (m, 2H); 1506 MS (ESI) 498 (MH), 500 (MH), 517 (MNH4); 1507 Anal. Calcd for: C22H17NO6SF4; C, 52.90; H, 3.43; N, 2.80. Found: C, 52.63; H, 3.60; N, 2.59.

EXAMPLE 195

()-N-hydroxy-N-1-(cyclohexyl)-2-4-4-(trifluoromethoxy)phenoxyphenylsulfonylethylformamide 1508 The title compound was prepared according to the procedures of example 75, except substituting cyclohexane carboxaldehyde for propionaldehyde and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-methoxylphenyl)phenyl methyl sulfone in example 75A. 1509 1H NMR (DMSO-d6) 9.86 (s, 0.5H), 9.50 (s, 0.5H), 8.13 (s, 0.5H), 7.89-7.97 (m, 2H), 7.75 (s, 0.5H), 7.47-7.51 (d, 2H, J7.8 Hz), 7.26-7.48 (m, 4H),4.21-4.26 (m, 0.5H), 4.01-3.97 (m, 0.5H), 3.56-3.41 (m, 4H), 0.56-1.7(m, 11H); 1510 MS (ESI) 486 (MH), 488 (MH), 505 (MNH4); 1511 Anal. Calcd for: C22H24NO6SF3.0.25H2O: C, 53.70; H, 5.01; N, 2.84. Found: C, 54.67; H, 5.35; N, 2.69.

EXAMPLE 196

()-(S) N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide

EXAMPLE 196A

(S)-4-4-(4-chlorophenoxy)phenylthiomethyl-2-oxazolidinone 1512 A 0 C. solution of 4-(4-chlorophenoxy)-benzenethiol (25.5 g, 108 mmol) in DMF (250 mL) was treated with K2CO3 (14.9 g, 108 mmol) followed by (S)-()-4-(4-toluene-sulfonyloxymethyl)-2-oxazolidinone (22.09 g, 83 mmol) J Chem. Soc. Perkin Trans. 1. 1994, 13, 1675. The reaction was allowed to stir overnight at ambient temperature, then partitioned between ethyl acetate and brine. The organics were washed with brine twice, dried, filtered, concentrated and purified via silica gel chromatography eluting with 5 to 20 % ethyl acetate/hexane to give 22.08 g (81% yield) of the title compound. 1513 MS (ESI) m/e 353 (MNH4).

EXAMPLE 196B

(S)-4-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-oxazolidinone 1514 A 0 C. mixture of 196A (3.6 g, 10 mmol) and NaHCO3 (2.26 g, 26 mmol) in 200 mL of methanol and 50 mL of water was treated with oxone (9.6 g, 27 mol), then stirred at room temperature for 3h, after which time the reaction was quenched with water and extracted with ethyl acetate. The organics were dried, filtered, and concentrated to give 3.53 g (96%) of the title compound. 1515 MS (ESI) m/e 368 (MH), 385 (MNH4), 390 (MNa).

EXAMPLE 196C

(S)-2-amino3-4-(4-chlorophenoxy)phenylsulfonyl-1-propanol 1516 A mixture of 196B (3.53 g, 9.6 mmol) and NaOH (0.62 g, 15 mmol) in ethanol (20 mL) was stirred at reflux for 30 h, then concentrated and partinioned between brine and CH2Cl2. The aqueous layer was back extracted with CH2Cl2 twice and the combined organics were washed with brine, dried, filtered, and concentrated to give 3.0 g (92% ) of the title compound. 1517 MS (ESI) m/e 342 (MH), 364 (MNa).

EXAMPLE 196D

()(S)-N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethylhydroxylamine 1518 A solution of 196C (9.89 g, 29 mmol) and 4-methoxybenzaldehyde (3.53 g, 29 mmol) in toluene (300 mL) was refluxed for 18 h in a Dean-Stark apparatus. The reaction was then concentrated and the crude product was dissolved in THF (200 mL), sequentially treated with triphenyl phosphine (9.1 g, 35 mmol), 1,5,5-trimethyl hydantoin (4.9 g, 35 mmol) and diethyl azodicarboxylate (5.5 g, 35-mmol). The reaction was concentrated and the residue was dissolved in chloroform (100 mL), cooled to 0 C., treated with 69 mL of sat. aq. NaHCO3, and benzyltriethylammonium chloride (0.726 g, 3.18 nunol) followed by dropwise addition of a solution of m-chloroperbenzoic acid (11 g, 32 mmol, 50%-Aldrich) in 100 mL CH2Cl2. The reaction was stirred at 0 C. for 7 h then partitioned between water and CH2Cl2. The organics were washed with aq. NaHSO3, water, brine, dried, filtered, and concentrated. The crude product was dissolved in 200 mL of methanol, treated with hydroxylamine hydrochloride (4 g, 58 mmol) and stirred at room temperature for 3 days. The reaction was then concentrated and the residue was partitioned between sat. aq. NaHCO3 and ethyl acetate. The organics were dried, filtered, concentrated and purified via silica gel chromatography eluting with 1 to 5% methanol/methylene chloride to give 1.29 g (9%) of the title compound. 1519 MS (ESI) m/e 482 (MH), 504 (MNa).

EXAMPLE 196E

() N-1-4-(4-chlorophenoxy)phenylsulfonylmethyl-2-(3,4,4-trimethyl-2,5-dioxo-1-imidazolidinyl)ethyl-N-hydroxyformamide 1520 Example 196E was converted to the title compound following the procedure of example 2F. 1521 mp 111 C.; 1522 D6.4 (c0.25).

EXAMPLE 197

()-N-hydroxy-N-1-4-4-(trifluorophenoxy)phenylsulfonylmethyl-2-(3,4,5-trimethoxyphenyl)ethylformamide 1523 The title compound was prepared according to the procedures of example 126, except substituting ethyl 3,4,5-trimethoxyphenoxyacetate (prepared from ethyl bromo-acetate and 3,4,5-trimethoxyphenol as in example 174A) for ethyl methoxyacetate and 4-(4-trifluoromethoxyphenoxy)phenyl methyl sulfone for 4-(4-trifluoromethylphenyl)phenyl methyl sulfone. 1524 1H NMR (DMSO-d6) 3.53-3.62 (m, 4H), 3.65-3.77 (m, 7H), 3.92-4.0 (m, 1H), 4.02-4.15 (m, 1H), 4.35-4.46 (bs, 0.5H), 4.85-4.97 (bs, 0.5H), 6.16 (d, 2H, J4 Hz), 7.16-7.30 (m, 4H), 7.47 (d, 2H, J9 Hz), 7.91 (d, 2H, J12 Hz), 7.96 (s, 0.5H), 8.21 (s, 0.5H), 9.68 (s, 0.5H), 10.08 (s, 0.5H); 1525 MS (ESI) 600 (MH); 1526 Anal. Calcd for: C26H26NO10SF3C, 51.91; H, 4.35; N, 2.32. Found: C, 51.90; H, 4.41; N, 2.26.