0001 The present invention relates to novel imidazotriazinones, to processes for their preparation and to their use as medicaments, in particular as inhibitors of cGMP-metabolizing phosphodiesterases. 0002 The published specificiation DE-OS 2811780 describes imidazotriazines as broncho-dilators having spasmolytic activity and inhibitory activity against phosphodiesierases which metabolize cyclic adenosine monophosphate (cAMP-PDEs, nomenclature according to Beavo: PDE III and PDE IV). An inhibitory action against phosphodiesterases which metabolize cyclic guanosine monophosphate cGMP-PDEs, nomeclature according to Beavo and Reifsnyder (Trends in Pharmacol. Sci. 11, 150-155, 1990) PDE I, PDE II and PDE V has not been described. Furthermore, FR-22 13 058, CH-59 46 71, DE-22 55 172, DE-23 64 076 and EP-000 9384 describe imidazotriazinones which do not have a substituted aryl radical in the 2 position and are likewise said to be bronchodilatators having cAMP-PDE-inhibitory action. 0003 WO-A-99/24433 likewise describes imidazotriazinones as inhibitors of cGMP-metabolizing phosphodiesterase; however, these compounds, by definition, all have a sulfonamide group in the phenyl ring in the position para to the alkoxy group. 0004 An increase in the cGMP concentration can lead to beneficial antiaggregatory, antithrombotic, antiprolific, antivasospastic, vasodilative, natriuletic and diuretic effects. It can influence the short- or long-term modulation of vascular and cardiac inotropy, of the pulse and of cardiac conduction (J. C. Stoclet, T. Keravis, N. Komas and C. Kugnier, Exp. Opin. Invest. Drugs (1995), 4 (11), 1081-1100). Inhibition of cGMP-PDEs can also enhance erections. Accordingly, such compounds are suitable for treatings erectile dysfunction. 0005 The present invention accordingly relates to novel imidazotriazinones of the general formula (I) 1

0006 in which 0007 R1 represents (C1-C6)-alkyl, 0008 R2 represents (C3-C8)-cycloalkyl or (C1-C12)-alkyl, 0009 R3 represents (C1-C6)-alkyl, 0010 R4 represents a radical of the formulae 2

0011 in which 0012 R5, R6 and R7 are identical or different and represent vinyl or (C1-C6)-alkyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of trifluoromethyl, halogen, (C1-C6)-alkoxy or by radicals of the formulae 3

0013 in which 0014 R8 represents hydrogen or (C1-C4)-alkyl, 0015 or 0016 R5, R6 and/or R7 represents (C6-C12)-aryl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of halogen, trifluoromethyl, nitro, cyano, carboxyl, (C1-C6)-alkyl and (C1-C6)-alkoxy 0017 or 0018 R5 represents quinolyl or a 5- to 6-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, which heterocycle may optionally be substituted up to 3 times, in the case of an N function also via this N function, by identical or different substituents from the group consisting of halogen and (C1-C6)-alkyl 0019 or 0020 R5 represents a radical of the formulae 4

0021 or NR9R10 0022 in which 0023 R9 and R10 are identical or different and represent hydrogen. (C1-C6)-alkyl or phenyl, 0024 or 0025 R4 represents carboxyl or represents a radical of the formulae 5

0026 COR13 or OR14, 0027 in which 0028 R11 and R12 are identical or different and represent hydrogen or (C1-C4)-alkyl, 0029 R13 represents (C1-C6)-alkyl, 0030 R14 represents (C1-C6)-alkyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of hydroxyl, phenyl or by a radical of the formula NR15R16, 0031 in which 0032 R15 and R16 are identical or different and represent hydrogen, phenyl or (C1-C4)-alkyl which for its part may be substituted by phenyl, 0033 or 0034 R4 represents a radical of the formula NHCONR17R18, 0035 in which 0036 R17 and R18 are identical or different and represent hydrogen or (C1-C6)-alkyl which is optionally substituted by hydroxyl or by a radical of the formulae 6

0037 or NR19R20, 0038 in which 0039 R19 and R20 are identical or different and represent hydrooen, phenyl or (C1-C6)-alkyl 0040 or 0041 R17 and R18 together with the nitrogen atom to which they are attached form a heterocyclic ring of the formulae 7

0042 in which 0043 R21 represents hydrogen or (C1-C6)-alkyl, 0044 a represents either 1 or 2, 0045 R22 represents hydroxyl or (C1-C6)-alkyl which is optionally substituted by hydroxyl, 0046 or 0047 R17 and/or R18 represent (C6-C12)-aryl which is optionally substituted by halogen, trifluoroethyl or by SCF3 0048 or 0049 R17 represents hydrogen and 0050 R18 represents a radical of the formula SOR23, 0051 in which 0052 R23 represents (C1-C6)-alkyl or (C6-12)-aryl which is optionally substituted by halogen, 0053 or represents a radical of the formulae 8

0054 or 0055 R4 represents a radical of the formula 0056 NHCOR24, 0057 in which 0058 R24 represents a radical of the formula 9

0059 in which 0060 R25 and R26 are identical or different and represent hydrogen, (C1-C6)-alkyl or (C1-C6)-alkoxycarbonyl, 0061 or 0062 R24 represents (C1-C6)-alkyl which is optionally substituted by (C6-C12)-aryl which for its part may be substituted by hydroxyl or (C1-C6)-alkoxy or 0063 (C1-C6)-alkyl optionally substituted by a radical of the fornula (SO2)bR27, 0064 in which 0065 b represents either 0 or 1 and 0066 R27 represents a radical of the formulae 10

0067 or 0068 R4 represents (C1-C12)-alkyl which is optionally substituted up to 3 times by identical or different radicals from the group consisting of hydroxyl, azide, phenyl or by radicals of the formulae NR28R29, OCOR30 or P(O)O-(C1-C6)-alkyl2, 0069 in which 0070 R28 and R29 are identical or different and represent hydrogen, phenyl or (C1-C6)-alkyl which is optionally substituted by hydroxyl, (C1-C6)-alkoxy or phenyl, 0071 or 0072 R28 and R29 together with the nitrogen atom to which they are attached form a heterocyclic ring of the formulae 11

0073 in which 0074 R31 and R32 are identical or different and represent hydrogen or (C1-C6)-alkyl 0075 R33 represents (C1-C6)-alkyl, benzyl, (C1-C6)-alkoxycarbonyl, (C1-C6)-alkylcarbonyl, carboxyl, pyridyl, pyrimidyl or phenyl which is optionally substituted by (C1-C6)-alkoxy, 0076 and 0077 R30 represents (C1-C6)-alkyl, 0078 or 0079 (C1-C12)-alkyl optionally substituted by triazolyl which for its part may be substituted up to 2 times by identical or different substituents from the group consisting of halogen, phenyl, tetrahydrofuran), tetrahydropyranyl, (C1-C6)-alkoxycarbonyl, aminocarbonyl or by (C1-C6)-alkyl, where the latter may optionally be substituted by hydroxyl, (C1-C6)-alkoxy or by a radical of the formulae NR34R35 or OCOR36, 0080 in which 0081 R34 and R35 are identical or different and represent hydrogen or (C1-C6)-alkyl, 0082 R36 represents (C1-C6)-alkyl, 0083 or 0084 R4 represents a radical of the formula COR37, 0085 in which 0086 R37 represents a radical of the formulae 12

0087 (CH2)cNR39R40 or CH2P(O)(OR41 )(OR42), 0088 in which 0089 R38 represents hydroen or (C1-C6)-alkyl, 0090 c represents either 0 or 1, 0091 R39 and R40 are identical or different and represent hydrooen or (C1-C6)-alkyl which is optionally substituted by hydroxyl, 0092 R41 and R42 are identical or different and represent (C1-C6)-alkyl, 0093 or 0094 R4 represents a 5-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, which heterocycle is optionally substituted altogether up to 3 times, in the case of an N function also via this N function, by identical or different substituents from the group consisting of halogen, trifluoromethyl or by phenyl which for its part may be mono- or polysubstituted by halogen or trifluoromethyl, 0095 and/or is optionally substituted by (C3-C6)-cycloalkyl, pyrryl or by (C1-C12)-alkyl which for its part may be substituted by cyano, trifluoromethyl, (C1-C6)-alkoxycarbonyl, (C1-C6)-alkoxy, amino or by phenyl or nitro-substituted phenyl, 0096 and/or may optionally be substituted by NR43R44, NHCOCOR45, NHCOR46, 13

0097 in which 0098 R43 and R44 are identical or different and represent hydrogen, benzyl, (C1-C6)-alkyl or phenyl which is optionally substituted by halogen or trifluoromethyl, 0099 R45 represents (C1-C6)-alkoxy, 0100 R46 represents (C1-C6)-alkyl or phenyl, 0101 R47 represents hydroxyl, (C1-C6)-alkoxy or a radical of the formula OCOR49, 0102 in which 0103 R49 represents (C1-C4)-alkyl 0104 R48 represents a radical of the formula CH2CN or phenyl which is optionally substituted by halogen, trifluoromethyl or (C1-C6)-alkoxy, 0105 and their tautomers and their pharmaceutically acceptable salts, hydrates and prodrugs. 0106 Depending on the substitution pattern, the compounds of the general formula (I) according to the invention may exist in stereoisomeric forms which are either like image and mirror image (enantiomers), or which are not like image and mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemic forms can, just like the diastereomers, be separated in a known manner into the stereoisomerically uniform constituents. 0107 Certain compounds of the general formula (I) may furthermore be present in tautomeric forms. This is known to the person skilled in the art, and such compounds are also within the scope of the invention. 0108 Physiologically acceptable, i.e. pharmaceutically acceptable, salts can be salts of the compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid, or salts with organic carboxylic or sulfonic acids such as, for example, acetic acid, propionic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid or naphthalenedisulfonic acid. 0109 Pharmaceutically acceptable salts that may be mentioned are also salts with customary bases, such as, for example, alkali metal salts (for example sodium salts or potassium salts), alkaline earth metal salts (for example calcium salts or magnesium salts) or ammonium salts derived from ammonia or organic amines such as, for example, diethyl amine, triethlyamine, ethyldiisopropylamine, procaine, dibenzylamine, N-methylmorpholine, dihydroabietylamine or methylpiperidine. 0110 Hydrates according to the invention are those forms of the compounds of the above general formula (I) which, in solid or liquid state, form a molecular compound (solvate) with water by hydrataion. In the hydrates, the water molecules form an adduct by intramolecular forces, in particular hydrogen bonds. Solid hydrates contain water as water of crystallization in stoichiometric ratios, it not being necessary for the water molecules to be equivalent with respect to their binding state. Examples of hydrates are sesquihydrates, monohydrates dihydrates or trihydrates. Also suitable are the hydrates of salts of the compounds according to the invention. 0111 Prodrugs according to the invention are forms of the compounds of the above general formula (I) which, for their part, may be biologically active or inactive, but which can be converted into the corresponding biologically active form (for example metabolically, solvolytically or by other means). 0112 C1-C12)-Alkyl denotes a straight-chain or branched alkyl radical having 1 to 12 carbon atoms. Examples which may be mentioned are: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl and n-hexyl. Derived from this definition are, in an analogous manner, the corresponding alkyl groups having fewer carbon atoms, such as, for example, (C1-C6)-alkyl and (C1-C4)-alkyl. Generally, preference is given to (C1-C4)-alkyl. 0113 (C3-C8)-Cycloalkyl denotes a cyclic alkyl radical having 3 to 8 carbon atoms. Examples which may be mentioned are: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. Derived from this definition are, in an analogous manner, the corresponding cycloalkyl groups having fewer carbon atoms, such as, for example, (C3-C5)-cycloalkyl. Preference is given to cyclopropyl, cyclopentyl and cyclohexyl. 0114 (C1-C6)-Alkoxy denotes a straight-chain or branched alkoxy radical having 1 to 6 carbon atoms. Examples which may be mentioned are: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy and n-hexoxy. Derived from this definition are, in an analogous manner, the corresponding alkoxy groups having fewer carbon atoms, such as, for example, (C1-C6)-alkoxy and (C1-C4)-alkoxy. In general, preference is given to (C1-C4)-alkoxy. 0115 Also derived from this definition is the meaning of the corresponding component of other, more complex substituents, such as, for example, alkoxycarbonyl. 0116 (C6-C12-Aryl denotes an aromatic radical having 6 to 12 carbon atoms. Examples which may be mentioned are: phenyl and naphthyl. 0117 5- to 6-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O denotes either a heteroaromatic radical which is attached via a ring carbon atom of the heteroaromatic compound or, if appropriate, also via a ring nitrogen atom of the heteroaromatic compound; examples which may be mentioned are: pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl or isoxazolyl, preference being given to pyridyl, pyrimidyl, pyridazinyl, furyl and thienyl, or denotes a saturated heterocycle which is attached via a ring carbon atom or a ring nitrogen atom, or denotes a (C5-C6)-cycloalkyl radical as mentioned above: examples which may be mentioned are: tetrahydrofuryl, pyrrolidiyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, cyclopentyl and cyclohexyl, piperidinyl, morpholinyl and pyrrolidinyl being preferred. 0118 Preference is given to compounds of the general formula (I) according to the invention 0119 in which 0120 R1 represents (C1-C4)-alkyl, 0121 R2 represents cyclopentyl, cycloheptyl or (C1-C10)-alkyl, 0122 R3 represents (C1-C4)-alkyl, 0123 R4 represents a radical of the formulae 14

0124 in which 0125 R5, R6 and R7 are identical or different and represent vinyl or (C1-C4)-alkyl which is optionally substituted up 3 times by identical or different substituents from the group consisting of trifluoromethyl, chlorine, (C1-C4)-alkoxy or by radicals of the formulae 15

0126 in which 0127 R8 represents hydrogen, methyl or ethyl, 0128 or 0129 R5, R6 and/or R7 represent phenyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of halogen, trifluoromethyl, nitro, cyano, carboxyl, (C1-C4)-alkyl and (C1-C4)-alkoxy 0130 or 0131 R5 represents quinolyl or a radical of the formulae 16

0132 which may optionally be substituted up to 2 times by identical or different substituents from the group consisting of chlorine and (C1-C4)-alkyl 0133 or 0134 R5 represents a radical of the formulae 17

0135 in which 0136 R9 and R10 are identical or different and represent hydrogen (C1-C6)-alkyl or phenyl, 0137 or 0138 R4 represents carboxyl or represents a radical of the formulae 18

0139 COR13 or OR14, 0140 in which 0141 R11 and R12 are identical or different and represent hydrogen or (C1-C4)-alkyl, 0142 R13 represents (C1-C4)-alkyl, 0143 R14 represents (C1-C4)-alkyl which is optionally substituted up 3 timnes by identical or different substituents from the group consisting of hydroxyl, phenyl or by a radical of the formula NR15R16, 0144 in which 0145 R15 and R16 are identical or different and represent hydrogen, phenyl or (C1-C4)-alkyl which for its part maay be substituted by phenyl, 0146 or 0147 R4 represents a radical of the formula NHCONR17R18, 0148 in which 0149 R17 and R18 are identical or different and represent hydrogen or (C1-C4)-alkyl which is optionally substituted by hydroxyl or by a radical of the formulae 19

0150 in which 0151 R19 and R20 are identical or different and represent hydrogen, phenyl or (C1-C4)-alkyl 0152 or 0153 R17 and R18 together with the nitrogen aton to which they are attached form a heterpcuc;oc ring of the formulae 20

0154 in which 0155 R21 represents hydrogen or (C1-C4)-alkyl, 0156 a represents either 1 or 2, 0157 R22 represents hydroxyl or (C1-C4)-alkyl which is optionally substituted by hydroxyl, 0158 or 0159 R17 and/or R18 represent phenyl which is optionally substituted by chlorine, trifluoroethyl or by SCF3 0160 or 0161 R17 represents hydrogen and 0162 R18 represents a radical of the formula SO2R23, 0163 in which 0164 R23 represents (C1-C4)-alkyl or phenyl which is optionally substituted by halogen, 0165 or represents a radical of the formulae 21

0166 or 0167 R4 represents a radical of the formula 0168 NHCOR24, 0169 in which 0170 R24 represents a radical of the formula 22

0171 in which 0172 R25 and R26 are identical or different and represent hydrogen, (C1-C4)-alkyl or (C1-C4)-alkoxycarbonyl, 0173 or 0174 R24 represents (C1-C4)-alkyl which is optionally substituted by phenyl which for its part may be substituted by hydroxyl or (C1-C4)-alkoxy or 0175 (C1 -C4)-alkyl optionally substituted by a radical of the formula (SO2)bR27, 0176 in which 0177 b represents either 0 or 1 and 0178 R27 represents a radical of the formulae 23

0179 or 0180 R4 represents (C1-C11)-alkyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of hydroxyl, azide, phenyl or by radicals of the formulae NR28R29, OCOR30 or P(O)O(C1-C6)-alkyl2, 0181 in which 0182 R28 and R29 are identical or different and represent hydrogen, phenyl or (C1-C4)-alkyl which is optionally substituted by hydroxyl (C1-C4)-alkoxy or phenyl, 0183 or 0184 R28 and R29 together with the nitrogen atom to which they are attached form a heterocyclic ring of the formulae 24

0185 in which 0186 R31 and R32 are identical or different and represent hydrogen or (C1-C4)-alkyl 0187 R33 represents (C1-C4)-alkyl, benzyl, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylcarbonyl, carboxyl, pynrdyl, pyrimidyl or phenyl which is optionally substituted by (C1-C4)-alkoxy, 0188 and 0189 R30 represents (C1-C6)-alkyl, 0190 or 0191 (C1-C11)-alkyl is optionally substituted by triazolyl which for its part may be substituted up to 2 times by identical or different substituents from the group consisting of halogen, phenyl, tetrahydrofuranyl, tetrahydropyranyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl or by (C1-C4)-alkyl, where the latter may optionally be substituted by hydroxyl, (C1-C4)-alkoxy or by a radical of the formulae NR34R35 or OCOR36, 0192 in which 0193 R34 and R35 are identical or different and represent hydrogen or (C1-C4)-alkyl, 0194 R36 represents (C1-C4)-alkyl, 0195 or 0196 R4 represents a radical of the formula OR37, 0197 in which 0198 R37 represents a radical of the formulae 25

0199 (CH2)cNR39R40 or CH2P(O)(OR4 1)(OR42), 0200 in which 0201 R38 represents hydrogen or (C1-C4)-alkyl, 0202 c represents either 0 or 1, 0203 R39 and R40 are identical or different and represent hydrogen or (C1-C4)-alkyl which is optionally substituted by hydroxyl, 0204 R41 and R42 are identical or different and represent (C1-C4)-alkyl, 0205 or 0206 R4 represents a radical of the formula 26

0207 which is optionally substituted altogether up to 3 times, in the case of the pyrazole also via the N function, by identical or different substitutents from the group consisting of chlorine, trifluoromethyl or by phenyl which for its part may be mono- or polysubstituted by chlorine or trifluoromethyl, 0208 and/or is optionally substituted by cyclopentyl, cyclohexyl, pyrryl or by (C1-C12)-alkyl which for its part may be substituted by cyano, trifluorornethyl, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkoxy, amino or by phenyl or nitro-substituted phenyl, 0209 and/or may optionally be substituted by NR43R44, NHCOCOR45, NHCOR46, 27

0210 in which 0211 R43 and R44 are identical or different and represent hydrogen, benzyl, (C1-C4)-alkyl or phenyl which is optionally substituted by halogen or trifluoromethyl, 0212 R45 represents (C1-C5)-alkoxy, 0213 R46 represents (C1-C5)-alkyl or phenyl, 0214 R47 represents hydroxyl, (C1-C4)-alkoxy or a radical of the formula OCOR49, 0215 in which 0216 R49 represents (C1-C3)-alkyl 0217 R48 represents a radical of the formula CH2CN or phenyl which is optionally substituted by chlorine, trifluoromethyl or (C1-C4)-alkoxy, 0218 and their tautomers and their pharmaceutically acceptable salts, hydrates and prodrugs. 0219 Particular preference is given to compounds of the general formula (I) according to the invention, 0220 in which 0221 R1 represents (C1-C4)-alkyl, 0222 R2 represents cyclopentyl, cyclohexyl, cycloheptyl or (C1-C10)-alkyl, 0223 R3 represents (C1-C4)-alkyl, 0224 R4 represents a radical of the formulae 28

0225 in which 0226 R5, R6 and R7 are identical or different and represent vinyl or (C1-C4)-alkyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of trifluoromnethyl, chlorine, (C1-C4)-alkoxy or by radicals of the formulae 29

0227 in which 0228 R8 represents hydrogen, methyl or ethyl, 0229 or 0230 R5, R6 and/or R7 represent phenyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of halogen, cyano, (C1-C4)-alkyl and (C1-C4)-alkoxy 0231 or 0232 R5 represents a radical of the formulae 30

0233 which may optionally be substituied up to 2 times by identical or different substituents from the group consisting of chlorine and (C1-C4)-alkyl 0234 or 0235 R5 represents a radical of the formula NR9R10, 0236 in which 0237 R9 and R10 are identical or different and represent hydrogen, (C1-C4)-alkyl or phenyl, 0238 or 0239 R4 represents carboxyl or represents a radical of the formulae 31

0240 or 0241 COR13 or OR14, 0242 in which 0243 R13 represents (C1-C4)-alkyl, 0244 R14 represents (C1-C4)-alkyl which is optionally substituted up to 3 times by identical or different substiuents from the group consisting of hydroxyl or by a radical of the formula NR15R16, 0245 in which 0246 R15 and R16 are identical or different and represent hydrogen or (C1-C4)-alkyl which for its part may be substituted by phenyl, 0247 or 0248 R4 represents a radical of the formula NHCONR17R18, 0249 in which 0250 R17 and R18 are identical or different and represent hydrogen or (C1-C4)-alkyl which is optionally substituted by hydroxyl, 0251 or 0252 R17 and R18 together with the nitrogen atom to which they are attached form a helerocyclic ring of the formulae 32

0253 in which 0254 R21 represents hydrogen or (C1-C4)-alkyl, 0255 or 0256 R17 and/or R18 represent phenyl which is optionally substituted by chlorine, trifluoroethyl or by SCF3 0257 or 0258 R17 represents hydrogen and 0259 R18 represents a radical of the formula SO2R23, 0260 in which 0261 R23 represents (C1-C4)-alkyl or phenyl which is optionally substituted by halogen, 0262 or represents a radical of the formulae 33

0263 or 0264 R4 represents a radical of the formula 0265 NHCOR24, 0266 in which 0267 R24 represents (C1-C4)-alkyl which is optionally substituted by phenyl which for its part may be substituted by hydroxyl or (C1-C4)-alkoxy or 0268 (C1-C4)-alkyl is optionally substituted by a radical of the formula (SO2)bR27, 0269 in which 0270 b represents either 0 or 1 and 0271 R27 represents a radical of the formulae 34

0272 or 0273 R4 represents (C1-C6)-alkyl which is optionally substituted up to 3 times by identical or different substituents from the group consisting of hydroxyl, phenyl or by radicals of the formulae NR28R29 or OCOR30, 0274 in which 0275 R28 and R29 are identical or different and represent hydrogen, phenyl or (C1-C4)-alkyl which is optionally substituted by hydroxyl, (C1-C4)-alkoxy or phenyl, 0276 or 0277 R28 and R29 together with the nitrogen atom to which they are attached form a heterocyclic ring of the formulae 35

0278 in which 0279 R31 and R32 are identical or different and represent hydrogen or (C1-C4)-alkyl 0280 R33 represents (C1-C4)-alkyl, benzyl, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylcarbonyl carboxyl, pyridyl, pyrimidyl or phenyl which is optionally substituted by (C1-C4)-alkoxy, 0281 and 0282 R30 represents (C1-C6)-alkyl, 0283 or 0284 (C1-C6)-alkyl is optionally substituted by triazolyl which for its part may optionally be substituted up to 2 times by identical or different substituents from the group consisting of (C1-C4)-alkyl, where the latter may optionally be substituted by hydroxyl or (C1-C4)-alkoxy, 0285 in which 0286 or 0287 R4 represents a radical of the formula COR37, 0288 in which 0289 R37 represents a radical of the formulae 36

0290 or (CH2)cNR39R40, 0291 in which 0292 R38 represents hydrogen or (C1-C4)-alkyl, 0293 c represents either 0 or 1, 0294 R39 and R40 are identical or different and represent hydrogen or (C1-C4)-alkyl which is optionally substituted by hydroxyl, 0295 or 0296 R4 represents a radical of the formula 37

0297 which is optionally substituted altogether up to 3 times, in the case of the pyrazole also via the N function, by identical or different substituents from the group consisting of trifluoromethyl or by phenyl which for its part may be mono- or polysubstituted by chlorine or trifluoromethyl, 0298 and/or is optionally substituted by cyclopentyl, cyclohexyl or by (C1-C6)-alkyl which for its part may be substituted by (C1-C4)-alkoxy, amino or by phenyl, 0299 and/or may optionally be substituted by NR43R44, NHCOR46, NHCOCH2R47 or COR48, 0300 in which 0301 R43 and R44 are identical or different and represent hydrogen, benzyl, (C1-C4)-alkyl or phenyl which is optionally substituted by halogen or trifluoromethyl, 0302 R46 represents (C1-C4)-alkyl or phenyl, 0303 R47 represents hydroxyl or (C1-C4)-alkoxy, 0304 R48 represents phenyl which is optionally substituted by chlorine, trifluoromethyl or (C1-C4)-alkoxy, 0305 and their tautomers and their pharmaceutically acceptable salts, hydrates and prodrugs. 0306 Very particular preference is given to the compounds according to the invention having the structures below: 38

0307 and their tautomers and their pharmaceutically acceptable salts, hydrates and prodrugs. 0308 The compounds of the general formula (I) according to the invention are obtained when 0309 A in the case that R4 is a radical as defined above which is attached via a nitrogen atom, compounds of the general formula (II) 43

0310 in which 0311 R1, R2 and R3 are as defined above 0312 are initially converted, by reaction with HNO3/CF3CO2H, into the compounds of the general formula (III) 44

0313 in which 0314 R1, R2 and R3 are as defined above, 0315 in a next step reduced with H2/PdC to give amines of the general formula (IV) 45

0316 in which 0317 R1, R2 and R3 are as defined above, 0318 and 0319 finally reacted with compounds of the general formula (V)

AD(V),

0320 in which 0321 if 0322 A represents the radicals R5, R6 or R7 listed above under R4, 0323 D represents the radical SO2Cl, 0324 and if 0325 A represents the radical R24 listed above under R4, 0326 D represents the radical COCl 0327 and if 0328 A represents the radicals R17 or R18 listed above under R4, 0329 D represents the radicals NHCOCl, NCO or SO2NCO, 0330 in inert solvents, if appropriate in the presence of a base and/or an auxiliary, 0331 or 0332 B if R4 represents a radical as defined above which is attached via NHCO, alternatively compounds of the general formula (IV) are initially reacted with a bifunctional spacer B and then with compounds of the general formula (VI)

HNR49R50(VI),

0333 in which 0334 if 0335 B denotes a radical of the formula ClCH2COCl, 0336 R49 and R50 together with the nitrogen atom to which they are attached are within the scope of the meaning of R27 given above, 0337 and if 0338 B denotes a radical of the formula ClCOOCCl3, 0339 R49 and R50 are within the scope of the meanings of R17 and R18 given above, 0340 and if 0341 B denotes a radical of the formula ClSO2NCO, 0342 R49 and R50 together with the nitrogen atom to which they are attached are within the scope of the meaning of R23 given above, 0343 if appropriate in an inert solvents, 0344 or 0345 C if R4 represents a radical as defined above which is attached via a carbon atom, compounds of the general formula (II) are initially converted by reaction with formaldehyde/HCl into the compounds of the general formula (VII) 46

0346 in which 0347 R1, R2 and R3 are as defined above, 0348 and then, by methods familiar to the person skilled in the art, reacted 0349 with amines to give the corresponiding benzylamines, 0350 with phosphites to give the corresponding phosphonates, 0351 with azide and subsequently alkynes to give the corresponding triazoles, 0352 or 0353 D if R4 represents a radical as defined above which is attached via CO or represents one of the heterocycles listed above, 0354 initially compounds of the general formula (II) are, by reaction with BrCH2COBr in the presence of AlCl3, converted into compounds of the general formula (VIII) 47

0355 in which 0356 R1, R2 and R3 are as defined above, 0357 and then, by methods familar to the person skilled in the art, reacted 0358 with SmJ2 lo give the corresponding acetophenones, 0359 with Br2/NaOH to give carboxylic acids and then with amines to give the corresponding amides, 0360 with NaBH4/NaOH to give epoxides and then with amines to give the corresponding -hydroxyamines. 0361 with KCN and then hydrazines to give the corresponding aminopyrazoles, 0362 with thioureas to give the corresponding 2-aminothiazoles, 0363 with thiomides to give the corresponding thiazoles 0364 with phosphates to give the corresponding -ketophosphonates, 0365 with amines to give the corresponding -aminoketones 0366 or 0367 E in the case that R4 is a radical as defined above which is attached via an oxygen atom, compounds of the general formula (IX) 48

0368 in which 0369 R1, R2 and R3 are as defined above 0370 are initially converted, by reaction with meta-chloroperbenzoic acid (m-CPBA) into compounds of the general formula (X) 49

0371 in which 0372 R1, R2 and R3 are as defined above, 0373 and then reacted with the corresponding amines of the general formula (XI)

HNR15R16(XI),

0374 in which 0375 R15 and R16 are as defined above. 0376 The processes according to the invention can be illustrated in an exemplary manner by the formula schemes below: 50

0377 Solvents which are suitable for the individual steps are the customary organic solvents which do not change under the reaction conditions. These preferably include ethers, such as diethyl ether, dioxane, tetrahydrofuran, dimethlyl ether, or hydrocarbons, such as benzene, toluene, xylene, hexane, cyclolhexane or mineral oil fractions, or halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane, trichloroethylene or chlorobenzene, or ethyl acetate, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone, dimethoxyethane or pyridine. It is also possible to use mixtures of the solvents mentioned. 0378 The reaction temperatures can generally be varied within a relatively wide range. In general, the reactions are carried out in a range of from 20 C. to 200 C., preferably from 0 C. to 70 C. 0379 The process steps according to the invention are generally carried out at atmospheric pressure. However, it is also possible to operate under elevated pressure or reduced pressure (for example in a range of from 0.5 to 5 bar). 0380 The reactions can be carried out, for example, in a temperature range of from 0 C. to room temperature and at atmospheric pressure. 0381 The compounds of the general formula (II) can be prepared by converting compounds of the general formula (XII) 55

0382 in which 0383 R3 is as defined above 0384 by reaction of the nitrile group into the corresponding amidines, reacting these initially with hydrazine and then with compounds of the general formula (XIII) 56

0385 in which 0386 R1 and R2 are as defined above, 0387 to the compounds of the general formula (XIV) 57

0388 in which 0389 R1, R2 and R3 are as defined above 0390 and then cyclizing these by action of POCl3 to give compounds of the general formula (II). For details of this process, reference can be made to WO-A-99/24433, the content of which is hereby included in its entirety by reference. 0391 Most of the compounds of the general formulae (III), (IV), (VII), (VIII), and (X) are novel and can be prepared as described above. 0392 The compounds of the general formulae (V), (VI), (XI), (XII), (XIII) and (XIV) are known per se or can be prepared by customary methods. 0393 Some of the compounds of the general formula (IX) are novel, and they can be prepared by converting compounds of the general formula (XV) 58

0394 in which 0395 R3 is as defined above 0396 by reaction of the nitrile group into the corresponding amidines, which are then reacted with hydrazine and subsequently with compounds of the general formula (XII) and finally cyclized with POCl3 to give the corresponding compounds of the general formula (IX). 0397 The compounds of the general formula (XV) are known per se or can be prepared by customary methods. 0398 The compounds of the general formula (I) according to the invention have an unforeseeable, useful spectrum of pharmacological action. 0399 They inhibit either one or more of the cGMP-metabolizing phosphodiesterases(PDE I, PDE II and PDE V). This results in an increase of cGMP. The differentiated expression of the phosphodiesterases in different cells, tissues and organs and the differentiated subcelluloar localization of these enzymes allows, in combination with the selective inhibitors according to the invention, the different cGMP-regulated processes to be addressed selectively. 0400 The compounds accordiong to the invention moreover intensify the action of substances, such as, for example, EDRF (endothelium-derived relaxing factor), ANP (atrial natriuretic peptide), of nitrovasodilators and other substances which increase the cGMP concentration by a mode different to that of phosphadiesterase inhibitors. 0401 Accordingly, the compounds of the general formula (I) according to the invention are suitable for the prophylaxis and/or treatment of disorders in which an increase of the cGMP concentration is beneficial, i.e. cGMP-related diseases. These include cardiovascular disorders, disorders of the urogenital system and cerebrovascular disorders. 0402 In the context of the present invention, the term cardiovascular disorders includes disorders such as, for example, hypertension, neuronal hypertonia, stable and unstable angina, peripheral and cardial vasculopathies, arrhythmiae, thromboembolic disorders and ischemias such as myocardial infarction, stroke, transitory and ischemic attacks, angina pectoris, obstruction of peripheral circulation, prevention of restenoses after thrombolysis therapy, percutaneous transluminal angioplasty (PTA), percutaneous transluminal coronary angioplasties (PTCA) and bypass. 0403 Furthermore, the compounds of the general formula (I) according to the invention may also be of importance for cerebrovascular disorders, cerebral ischemia, stroke, reperfusion damage, cerebral trauma, edema or cerebral thrombosis. 0404 In addition, the present compounds are also suitable for improving perception, concentration power, learning power or memory power after cognitive disorders, such as occur, for example, in situations/illnesses/syndromes such as mild cognitive impairment, age-associated learning and memory disorders, age-associated memory loss, vascular dementia, craniocerebral trauma, stroke, dementia which occurs after strokes (post-stroke dementia), post-traumatic craniocerebral trauma, general concentration disorders, concentration disorders in children with learning and memory problems, Alzheimier's disease, vascular dementia, dementia with Lewy bodies, dementia with degeneration of the frontal lobes including Pick's disease, Parkinson's disease, progressive nuclear palsy, dementia with corticobasal degeneration, amyolateral sclerosis (ALS). Huntington's disease, multiple sclerosis, thalamic degeneration, Creutzfeld-Jacob dementia, HIV dementia, schizophrenia with dementia or Korsakoff psychosis. 0405 Owing to their relaxing action on smooth muscles, they are suitable for treating disorders of the urogenital system such as hypertrophy of the prostate, incontinence and in particular for the treatment of erectile dysfunction and female sexual dysfunction. 0406 Activity of the phosphordiesterases (PDEs) 0407 The cGMP-stimulable PDE II, the cGMP-inhibitable PDE II and the cAMP-specific PDE IV were isolated either from porcine or bovine heart myocardium. The Ca2-calmodulin-stimulable PDE I was isolated from porcine aorta, porcine brain or preferably from bovine aorta. The cGMP-specific PDE V was obtained from porcine small intestine, porcine aorta, human blood platelets and preferably from bovine aorta. Purification was carried out by anionic exchange chromatography on MonoQR Pharmacia essentially according to the method of M. Hoey and Miles D. Houslay, Biochemical Pharmacology, Vol. 40, 193-202 (1990) and C. Lugman et al. Biochemical Pharmacology, Vol.35 1743-1751 (1986). 0408 The enzyme activity was determined in a test batch of 100 l in 20 mM tris/HCl buffer pH 7.5 which contains 5 mM MgCl2, 0.1 mg/ml bovine serum albumin and either 800 Bq of 3HcAMP or 3HcGMP. The final concentration of the corresponding nucleotides is 106 mol/l. The reaction is started by addition of the enzyme and the amount of enzyme is proportioned such that about 50% of the substrate is converted during the incubation time. To test cGMP-stimulate PDE II, 3HcAMP is used as substrate and 106 mol/l unlabeled cGMP are added to the mixture. To test Ca2-calmodulin-dependent PDE I, 1 M of CaCl2 and 0.1 M of calmodulin are additionally added to the reaction mixture. The reaction is stopped by addition of 100 l of acetonitrile which contains 1 mM of cAMP and 1 mM of AMP. 100 l of the reaction mixture are separated by HPLC, and the products of the separation are determined on-line in a quantitative manner using a flow scintillation counter. What is measured is the substance concentration at which the reaction rate is reduced by 50%. Additionally, the phosphodiesterase 3H cAMP-SPA enzyme assay and the phosphodiesterase 3H cGMP-SPA enzyme assay from Amersham Life Science were used for tesling. The test was carried out according to the test protocol of the manufacturer. To detemine the activity of PDE II, the 3H cAMP SPA assay was used, and 106 M cGMP were added to the reaction mixture to activate the enzyme. To measure PDE I, 107 M calmodulin and 1 M CaCl2 were added to the reaction mixture. PDE V was measured using the 3H cGMP SPA assay. 0409 In principle, innhibition of one or more phosphodiesterases of this type results in an increase of the cGMP concentration. Thus, the compounds are of interest for all therapies in which an increase in the cGMP concentration is considered to be beneficial. 0410 The cardiovascular effects were investigated using normotensive and SH rats and dogs. The substances were administered intravenously or orally. 0411 The study for erection-triggering action was carried out using awake rabbitsH. Naganuma, T. Egashira, J. Fuji. Clinical and Experimental Pharmacology and Physiology 20, 177-183 (1993). The substances were administered orally or parenterally. 0412 The novel active compounds and their physiologically acceptable salts (for example hydrochlorides, maleates or lactates) can be converted in a known manner into the customary formulations, such as tablets, coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert non-toxic, pharmaceutically suitable excipients or solvents. In this case, the therapeutically active compound should in each case be present in a concentration of from approximately 0.5 to 90% by weight of the total mixture, i.e. in amounts which are sufficient in order to achieve the dosage range indicated. 0413 The formulations are prepared, for example, by extending the active compounds using solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, it optionally being possible, for example, to use organic solvents as auxiliary solvents if the diluent used is water. 0414 Administration is carried out in a customary manner, preferably orally, transdermally or parenterally, for example perlingually, buccally, intravenously, nasally, rectally or inhalatively. 0415 For human use, in the case of oral administration, doses of from 0.001 to 50 mg/kg, preferably 0.01 mg/kg-20 mg/kg, are generally administered. In the case of parenteral administration, for example nasally, buccally or inhalatively via mucosa, it is eood practice to use doses of 0.001 mg/kg-0.5 mg/kg. 0416 In spite of this, if appropriate it may be necessary to depart from the amounts mentioned, namely depending on the body weight or the administration route, on the individual response toward the medicament, the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it may be adequate to manage with less than the abovementioned minimum amounts, while in other cases the upper limit mentioned has to be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these into several individual doses over the course of the day. 0417 The compounds according to the invention are also suitable for use in veterinary medicine. For use in veterinary medicine, the compounds or their non-toxic salts can be administered in a suitable formulation in accordance with general veterinary practice. Depending on the kind of animal to be treated, the veterinary surgeon can determine the administration route and the dosage. 0418 The present invention is illustrated by the examples below, however, the invention is by no means limited by these examples. 0419 In the structural formulae given below which contain the radical 59

0420 this always denotes 60

0421 Preparation of the precursors

EXAMPLE 1A

2-Butyrylaminopropionic acid 0422

0423 22.27 g (250 mmol) of D,L-alanine and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0 C. 59.75 g (550 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred at room temperature for 1 hour and at 40 C. for one hour. After cooling to 10 C., 26.64 g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred at 10 C. for 2 hours and at room temperature for one hour. With ice-cooling, 125 ml of water are added dropwise, and the reaction mixture is stirred at room temperature for 15 minutes. The aqueous phase is evaporated to dryness, the residue is triturated with acetone and the mother liquor is filtered off with suction. Following removal of the solvent, the residue is chromatographed. The resulting product is dissolved in 3N aqueous sodium hydroxide solution, and the resulting solution is evaporated to dryness. The residue is taken up in conc. HCl and again evaporated to dryness. The residue is triturated with acetone, the precipitated solid is filtered off with suction and the solvent is removed under reduced pressure. This gives 28.2 g (71%) of a viscous oil which crystallizes after some time. 0424 200 MHz 1H-NMR (DMSO-d6): 0.84 (t, 3H); 1.22 (d, 3H); 1.50 (hex, 2H); 2.07 (t, 2H); 4.20 (quin., 1H); 8.09 (d, 1H).

EXAMPLE 2A

2-Butyrylaminobutyric acid 0425

0426 25.78 g of 2-aminobutyric acid (250 mmol) and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0 C. 59.75 g (550 mmol) of trimethlylsilyl chloride are added dropwise, and the solution is stirred at room temperature for 1 hour and at 40 C. for one hour. After cooling to 10 C., 26.64 g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred at 10 C. for 2 hours and at room temperature for one hour. With ice-cooling, 125 ml of exhaler are added dropwise, and the reaction mixture is stirred at room temperature for 15 minutes. Aqueous sodium hydroxide solution is added to the organic phase, and the organic solvent is removed under reduced pressure. The residue is acidified and the precipitated solid is triturated once with water and twice with petroleum ether and dried under reduced pressure at 45 C. 29.1 g (67%) of a colorless solid. 0427 200 MHz 1H-NMR (DMSO-d6):0.88 ( 2t, 6H); 1.5 (quart., 2H); 1.65 (m, 2H); 2.09 (t, 2H); 4.10 (m, 1H) 8.01 (d, 1H); 12.25 (s,m 1H).

EXAMPLE 3A

2-(2-Ethyl)butanoylaminopropionic acid 0428

0429 24.5 g (0.275 mol) of D,L-alanine are initially charged in 250 ml of dichloromethane, and 61.2 g (0.605 mol) of triethylamine are added. The mixture is cooled to 0 C., and 65.7 g (0.605 mol) of trimetlhylsilyl chloride are added. The mixture is stirred at room temperature for one hour and at 40 C. for one hour. The mixture is cooled to 10 C., and 37 g (0.275 mol) of 2-ethylbutyryl chloride are slowly added dropwise. The mixture is stirred at 10 C. for two hours and at room temperature overnight. The mixture is cooled in an ice bath, and 150 ml of water are added. 50 g (1.25 mol) of NaOH, dissolved in 100 ml of water, are added and the aqueous phase is separated off and concentrated. The residue is again taken up in water and acidified with concentrated hydrochloric acid, the aqueous solution is extracted repeatedly with dichloromethane and the organic phase is dried over Na2SO4 and concentrated. 0430 Yield: 43.55 g (84.6% of theory) 0431 200 MHz 1H-NMR (CDCl3): 0.91 (t, 6H); 1.5 (d, 3H); 1.52-1.73 (m, 4H); 1.99 (m, 1H); 4.61 (quin, 1H); 6.25 (d, 1H); 6.76 (bs, 1H).

EXAMPLE 4A

2-(2,2-Dimethy)pentanoylaminopropionic acid 0432

0433 48.04 g (344.2 mmol) of D,L-alanine methyl ester hydrochloride and 76.67 g (757.2 mmol) of triethylamine are dissolved in 600 ml of dichloromethane, and 56 g (344.2 mmol) of 2,2-dimethylpentanoyl chloride in 50 ml of dichloromethane are added dropwise at 0 C. The mixture is stirred at RT for 2 h, filtered off and washed with 10% strength HCl solution, saturated sodium bicarbonate solution and saturated sodium chloride solution. The mixture is dried over sodium sulfate and then concentrated. The residue is taken up in methanol, and a solution of 55 g (1377 mmol) of sodium hydroxide in 300 l of waler is added. The mixture is stirred at RT for 2 hours and then filtered off, and the methanol is evaporated under reduced pressure. The aqueous phase is acidified using concentrated hydrochloric acid solution and extracted with ethyl acetate (2). The combined ethyl acetate phases are dried over sodium sulfate and concentrated. The residue is crystallized from ether. 0434 Yield: 30 g (40.5%) 0435 M.p.: 168 C.

EXAMPLE 5A

2-Heptanoylaminopropionic acid 0436

0437 30 g (291 mmol) of D,L-alaninie methyl ester hydrochloride and 64.77 g (640 mmol) of triethylamine are initially charged in 300 ml of dry methylene chloride at 0 C. 43.24 g (291 mmol) of heptanoyl chloride in 50 ml of methylene chloride are added dropwise. The mixture is allowed to warm to RT and stirred at this temperature for 2 h. The precipitate is filtered off and the methylene chloride phase is extracted with saturated sodium bicarbonate solution and with saturated sodium chloride solution and dried over sodium sulfate. The solvent is removed under reduced pressure and the residue is dissolved in 300 ml of methanol. 300 ml of water, in which 46.55 g (1164 mmol) sodium hydroxide are dissolved, are added to this solution, and the mixture is stirted at RT for 2 h. The mixture is filtered, the methanol is evaporated using a rotary evaporator and the aqueous phase that remains is acidified to pH 1-2 using conc. Hcl. The precipitated product is filtered off and dried. Extraction of the aqueous phase with ethyl acetate gives a second product fraction. 0438 Yield: 50 g (85.4%) 0439 1H-NMR (CD3OD): 0.9 (t, 3H); 1.2-1.4 (m, 9H); 1.6 (quin., 2H); 2.2 (t, 2H); 4.38 (quar., 1H).

EXAMPLE 6A

2 -Octanoylaminopropionic acid 0440

0441 The preparation is carried out analogously to the procedure of example 1A using 16.5 g (0.185 mol) of D,L-alanine. 41.23 g (0.407 mol) of triethylamine, 44.27 g (0.407 mol) of trimethylsily)l chloride and 30.12 g (0.185 mol) of octanoyl chloride. The product crystallizes from toluene/n-hexane. 0442 Yield: 34.3 g (86%) 0443 1H-NMR (CD3OD): 0.9 (t, 3H); 1.2-1.4 (m, 11H); 1.6 (quin. 2H); 2.2 (t, 2H); 4.35 (quar 1H).

EXAMPLE 7A

2-Decanoylaminopropionic acid 0444

0445 The preparation is carried out analogously to the procedure of example 4A using 19.0 o (184 mmol) of D,L-alaninie methyl ester hydrochloride and 35.14 g (184 mmol) of decanoyl chloride. 0446 Yield: 37.3 g (83.2%) 0447 1H-NMR (CD3OD): 0.9 (t, 3H); 1.2-1.4 (m, 15H); 1.6 (m, 2H); 2.2 (t, 2H); 4.35 (quar., 1H).

EXAMPLE 8A

2-(2-Ethyl)octanoylaminopropionic acid 0448

0449 18.6 g (0.211 mol) of D,L-alaninie and 46.6 g (0.41 mol) of triethylamine are initially charged in 300 ml of dichloromethane. At 0 C., 50.09 g (0.461 mol) of trimethylsilyl chloride are added dropwise, and the mixture is stirred at room temperature for 1 h and then at 40 C. for 1 h. The solution is cooled to 10 C., and 40 g (0.21 mol) of 2-ethyloctanoyl chloride in 50 ml of dichloromethane are added dropwise. The mixture is stirred at room temperature overnight, 100 ml of water are then added dropwise with ice-cooling and the mixture is stirred for 10 minutes. The phases are separated, the aqueous phase is reextracted twice with in each case 100 ml of dichloromethane and the combined organic phases are dried over sodium sulfate and concentrated under reduced pressure. The residue is crystallized from toluene by addino n-hexane and is dried at 60 C. 0450 Yield: 3.9 g (78.2%) 0451 1H-NMR (CDCl3): 0.9 (m, 6h); 1.25 (pseudo s, 8H); 1.45 (d, 3H); 1.4-1.7 (m, 4H); 2.0 (m, 1H); 4.6 (quin. 1H); 6.1 (d, 1H).

EXAMPLE 9A

2-Cyclopentanoylaminopropionic acid 0452

0453 16.8 g (0.189 mol) of D,L-alanine and 41.98 g (0.415 mol) of triethylamine are initially charged in 200 ml of dichloromethane. At 0 C., 45.07 g (0.415 mol) of trimethylsilyl chloride are added dropwise, and the mixture is stirred at room temperature for 1 h and then at 40 C. for 1 h. The solution is cooled to 100 C., and 25 g (0.189 mol) of cyclopentanecarbonyl chloride are added dropwise. The mixture is stirred at 10 C. for 2 h and at room temperature for 1 h. With ice-cooling, 100 ml of water are added dropwise, the mixture is stirred for 10 min. and the resulting precipitate is filtered off with suction. The precipitate is washed with 300 ml of water and then with 300 ml of diethyl ether and subsequently dried at 60 C. 0454 Yield: 25.8 g (73.9% of theory) 0455 1H-NMR (CD3OD): 1.35 (d, 3H); 1.5-1.9 (m, 8H); 2.7 (quin, 1H); 4.5 (quar., 1H):

EXAMPLE 10A

2-Cyclopentanoylaminobutyric acid 0456

0457 10.31 g of 2-aminobutyic acid (100 mmol) and 22.26 g (220 mmol) of triethylamine are dissolved in 100 ml of dichloromethane, and the solution is cooled to 0 C. 23.90 g (220 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred at room temperature for 1 hour and at 40 C. for one hour. After cooling to 10 C., 13.26 g (100 mmol) of cyclopentanecarbonyl chloride are added dropwise, and the resulting mixture is stirred at 10 C. for 2 hours and at room temperature for one h. 0458 With ice-cooling, 50 ml of water are added dropwise, and the reaction mixture is stirred at room temperature for 15 minutes. The mixture is diluted with water and dichloromethane and the resulting precipitate is filtered off with suction: 11.1 g (55%) ol a colorless solid. The dichloromethane phase is dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is triturated with toluene and the precipitate is filtered off with suction: 5.75 g (28%) of a colorless solid. 0459 200 MHz 1H-NMR (DMSO-d6): 0.88 (t, 3H); 1.61 (m, 10H); 2.66 (m, 1H); 4.09 (hex., 1H); 7.97 (d, 1H); 12.44 (s, 1H).

EXAMPLE 11A

2-Cycloheptanoylaminopropionic acid 0460

0461 The preparation is carried out analogously to the procedure of example 4A using 20 g (143 mmol) of D,L-alanine methyl ester hydrochloride and 23.02 g (143 mmol) of cycloheptanoyl chloride. 0462 Yield: 16 g (52.4%) 0463 1H-NMR (CD3OD): 1.35 (d, 3H); 1.45-1.65 (m, 8H); 1.7-1.95 (m, 4H); 2.35 (m, 1H); 4.25 (quar., 1H).

EXAMPLE 12A

2-Ethoxybenzonitrile 0464

0465 25 g (210 mmol) of 2-hydroxybenzonitrile, 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide are refluxed in 500 ml of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colorless liquid. 0466 200 MHz 1H-NMR (DMSO-d6): 1.48 (t, 3H); 4.15 (quart., 2H); 6.99 (dt, 2H); 7.51 (dt, 2H).

EXAMPLE 13A

2-Ethoxybenzamidine hydrochloride 0467

0468 21.4 g (400 mmol) of ammonium chloride are suspended in 375 ml of toluene, and the suspension is cooled to 0 C. 200 ml of a 2 M solution of trimethylaluminum in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. Following addition of 29.44 g (200 mmol) of 2-ethoxybenzonitrile, the reaction mixture is stirred at 80 C. (bath) overnight. The cooled reaction mixture is, with ice-cooling, added to a suspension of 100 g of silica gel and 950 ml of chloroform, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction and the filter cake is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is triturated with a mixture of dichloromethane and methanol (9:1), the solid is filtered off with suction and the mother liquor is concentrated. This gives 30.4 g (76%) of a colorless solid. 0469 200 MHz 1H-NMR (DMSO-d6): 1.36 (t, 3H); 4.12 (quart., 2H); 7.10 (t, 1H); 7.21 (d, 1H); 7.52 (m, 2H); 9.30 (s, broad, 4H).

EXAMPLE 14A

2-Propoxybenzonitrile 0470

0471 75 g (630 mmol) of 2-hydroxybenzonitrile, 174 g (1.26 mol) of potassium carbonate and 232.3 g (1.89 mol) of n-propyl bromide in 1 l of acetone are refluxed overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. 0472 B.p.: 89 C. (0.7 mbar) 0473 Yield: 95.1 g (93.7% of theory)

EXAMPLE 15A

2-Propoxybenzamidine hydrochloride 0474

0475 21.41 g (400 ml) of ammonium chloride are suspended in 400 ml of toluene and cooled to 0-5 C. 200 ml of a 2 M solution of trimethylaluminum in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. Following addition of 32.2 g (200 mmol) of 2-propoxybenzonitrile, the reaction mixture is stirred at 80 C. (bath) overnight. The cooled reaction mixture is, with ice-cooling, added to a suspension of 300 g of silica gel and 2.85 ml of ice-cooled chloroform and stirred for 30 minutes. The mixture is filtered off with suction and the filter cake is washed with the same amount of methanol. The solvent is distilled off under reduced pressure, the residue is triturated in 500 ml of a mixture of dichloromethane and methanol (9:1), the solid is filtered off and the mother liquor is concentrated. The residue is triturated with petroleum ether and filtered off with suction. This gives 22.3 g (52%) of product. 0476 200 MHz 1H-NMR (CD3OD): 1.05 (t, 3H); 1.85 (sex. 2H); 4.1 (t, 2H); 7.0-7.2 (m, 2H); 7.5-7.65 (m, 2H).

EXAMPLE 16A

2-(2-Ethoxyphenyl)-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0477

0478 7.16 g (45 mmol) of 2-butanoylaminopropionic acid (example 1A) and 10.7 g of pynidine are dissolved in 45 ml of tetrahydrofuran and, after addition of a spatula tip of 4-dimethylaminopyridine, heated at reflux. 12.29 g (90 mmol) of monoethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted 3 times with ethyl acetate, and the extracts are dried over sodium sulfate and concentrated. The residue is taken up in 15 ml of ethanol and refluxcd with 2.15 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered. 0479 With ice-cooling, 2.25 g (45 mmol) of hydrazne monohydrate are added dropwise to a solution of 9.03 g (45 mol) of 2-ethoxybenzamidine hydrochloride (example 13A) in 45 ml of ethanol, and the mixture is stirred at room temperature for 10 minutes. The ethanolic solution described above is added dropwise to this suspension, and the mixture is stirred at 70 C. for 4 hours. The mixture is filtered, the solution is concentrated, the residue is partitioned between dichloromethane and water and the organic phase is, after drying over sodium sulfate, concentrated. 0480 The residue is taken up in 60 ml of 1,2-dichloroethane, and 7.5 ml of phosphorus trichloride are added dropwise. After 2 hours of stirring under reflux, the mixture is cooled, diluted with dichloromethane and extracted twice with saturated sodium bicarbonate solution. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography with ethyl acetate and crystallization give 4.00 g (28.0% of theory) of a white solid. 0481 1H-NMR (200 MHz, CDCl3): 1.02 (t, 3H), 1.56 (t, 3H), 1.89 (hex, 2H), 2.67 (s, 3H), 3.00 (t, 2H), 4.26 (quar, 2H), 7.05 (m, 2H), 7.50 (dt, 1H), 8.17 (dd, 1H), 10.00 (s, 1H); 0482 TLC: Rf0.42 (dichloromethane:methanol95:5).

EXAMPLE 17A

2-(2-Ethoxyphenyl)-5-ethyl-7-propyl-3H-imidazo5,1-f1,2,4triazin-4-one 0483

0484 The preparation is carried out analogously to the procedure of example 16A using 29.06 g (167.8 mmol) of 2-butanoylaminobutyric acid (Example 2A) and 33.6 (167.8 mmol) of 2-ethoxybenzamidine hydrochloride (Examlpe 13A). Purification is carried out by silica gel chromatography (mobile phase: CH2Cl2/CH3OH 50:1). 0485 Yied: 7.4 g (12.4%) 0486 Rf0.46 (CH2Cl2/CH3OH20:1) 0487 1H-NMR (200 MHz, CDCl3): 1.32 (t, 3H); 1.57 (t, 32H); 1.94 (m, 8H); 3.03 (quart, 2H); 3.64 (quin, 1H); 4.27 (quart, 2H); 7.06 (d, 1H); 7.12 (t, 1H); 7.50 (dt, 1H); 8.16 (dd, 1H); 9.91 (s, 1H).

EXAMPLE 18A

2-(2-Ethoxyphenyl)-5-methyl-7-(1-ethylpropyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0488

0489 The preparation is carried out analooouslv to the procedure of example 16A using 21.45 g (0.1 mol) of 2-(2-ethylbutyrlaminopropionic acid (example 3A) and 20.6 g (0.1 mol) of 2-ethoxybenzamidine hydrochloride (example 13A). Purification is carried out by silica gel chromatography using the mobile phase dichloromethane/methanol 60:1. 0490 Yield: 7.22 g (21.3% of theory). 0491 1H-NMR (200 MHz, CDCl3): 0.87 (t, 6H), 1.57 (t, 3H), 1.88 (m, 4H), 2.67 (s, 3H), 3.28 (m, 1H), 4.28 (quar, 2H), 7.05 (d, 1H), 7.13 (dt, 1H), 8.15 (dd, 1H).

EXAMPLE 19A

2-(2-Ethoxyphenyl)-5-METHYL-7-(1,1-dimethyLbutyl)-3H-imidazo5,1-f1,2,4triazine-4-one 0492

0493 The preparation is carried out analogously to the procedure of example 16A using 22.85 g (0.1 mol) of 2-(2,2-dimethyl)pentanoylaminopropionic acid (example 4A) and 20.6 g (0.1 mol) of 2-ethoxybenzamidine hydrochloride (example 13A). Purification is carried out by silica gel chromatography (mobile phase: CH1Cl2/CH3OH50:1). 0494 Yield: 6.56 g (I 8.5%) 0495 1H-NMR (200 MHz, CD3OD): 0.82 (t, 3H); 1.1 (m, 2H); 1.45 (t, 3H); 1.5 (s, 6H); 1.95 (m, 2H); 2.57 (s, 3h); 4.2 (quar., 2H); 7.1 (t, 1H); 7.18 (d, 1H); 7.52 (dt, 1H); 7.72 (dd, 1H).

EXAMPLE 20A

2-(2-Ethoxyphenyl)-5-methyl-7-hexyl-3H-imidazo5,1-f1,2,4triazin-4-one 0496

0497 The preparation is carried out analogously to the procedure of example 16A using 14.1 g (70 mmol) of 2-heptanoylaminopropionic acid (example 5A) and 14.05 g (70 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). The purification of the product is carried out by silica gel chromatography using the mobile phase petroleum ether/ethyl acetate 1:1. 0498 Yield: 3.5 g (14.1%) 0499 1-NMR (CD3OD): 0.9 (t, 3H); 1.3-1.45 (m, 6H); 1.4 (t, 3H); 1.7-1.9 (m, 2H); 2.15 (s, 3H); 3.1 (t, 2H); 4.2 (quar., 2H); 7.1 (t, 1H); 7.15 (d, 1H); 7.05 (td, 1H); 7.7 (dd, 1H).

EXAMPLE 21A

2-(2-Ethoxyphenyl)-5-methyl-7-heptyl-3H-imdazo-5,1-f1,2,4triazin-4-one 0500

0501 The preparaTion is carried out analogously to the procedure of example 16A using 14.7 g (68.1 mmol) of 2-octanoylaminopropionic acid (example 6A) and 13.66 g (68.1 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). The purification of the product is carried out by silica gel chromatoraphy using the mobile phase dichloromethane/methanol 50:1. 0502 Yield: 4.65 g (18.5%), oil 0503 1H-NMR (CD3OD): 0.85 (t, 3H); 1.2-1.4 (m, 8H); 1.45 (t, 3H); 2.8 (quin, 2H); 2.6 (s, 3H); 3.0 (t, 2H), 4.2 (quar, 2H); 7.1 (t, 1H); 7.2 (d, 1H); 7.55 (td, 1H), 7.7 (dd, 1H).

EXAMPLE 22A

2-(2-Ethoxyphenyl)-5-methyl-7-nonyl-3H-imidazo5,1-f1,2,4--triazin-4-one 0504

0505 The preparation is carried out analogously to the procedure of example 16A using 7.0 g (70 mmol) of 2-decanoylaminopropionic acid (example 7A) and 14.05 g (70 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). The purification of the product is carried out by silica gel chromatography using the mobile phase petroleum ether/ethyl acetate 1:1. 0506 Yield: 3.5 g (14.1%) 0507 1H-NMR (CD3OD): 0.9 (t, 3H); 1.3-1.45 (m, 6H); 1.4 (t, 3H); 1.7-1.9 (m, 2H); 2.15 (s, 3H); 3.1 (t, 2H); 4.2 (quar., 2H); 7.1 (t, 1H); 7.15 (d, 1H); 7.05 (td, 1H), 7.7 (dd, 1H).

EXAMPLE 23A

2-(2-Ethoxyphenyl)-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0508

0509 The preparation is carried out analogously to the procedure of example 16A using 10.95 g (45 mnmol) of 2-(2-ethyl)octanoylaminopropionic acid (example 8A) and 9.03 g (45 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). Purification is carried out by silica gel chromatography using cyclohexane/ethyl acetate. 0510 Yield: 7.22 g (21.3% of theory) 0511 1H-NMR (200 MHz, CDCl3): 0.75-0.90 (m, 6H), 1.10-1.40 (m, 8H), 1.50 (t, 3H), 1.80-2.05 (m, 4H), 2.70 (s, 3H), 3.40 (quin., 1H), 4.30 (t, 2H), 7.05-7.20 (pseudo quar, 2H), 7.50 (td, 1H), 8.20 (dd, 1H), 10.40 (s, 1H).

EXAMPLE 24A

2-(2-Propoxyphenyl)-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4triazin-4-one 0512

0513 The preparation is carried out analogously to the procedure of example 16A using 10.95 g (45 mmol of 2-(2-ethyl)octanoylaminopropionic acid (example 8A) and 9.66 g (45 mmol) of 2-propoxybenzamidine hydrochloride (example 13A). Purification of the product is carried out by silica gel chromatography using the mobile phase dichloromethane/methanol 60:1. 0514 Yield: 3.7 g (20%), yellow oil 0515 1H-NMR (CDCl3): 0.75-0.9 (m, 6H); 1.15 (t, 3h); 1.1-1.35 (m, 8H); 1.75-2.1 (m, 6h); 2.7 (s, 3H); 3.4 (quin, 1H); 4.2 (t, 2H); 7.05-7.2 (pseudo quar, 2H); 7.5 (td, 1H), 8.2 (dd, 1H); 10.2 (broad, 1H).

EXAMPLE 25A

2-(2-Ethoxyphenyl)-5-methyl-7-cyclopentyl-3H -imidazo5,1-f1,2,4-triazin-4-one 0516

0517 The preparaion is carried out analogously to the procedure of example 16A using 19.9 g (100 mmol) of 2-cyclopentanoylaminopropionic acid (example 9A) and 20 g (100 mmol) of ethoxybenzamidine hydrochloride (example 13A). Purification is carried out by silica gel chromatography using methylene chloride/methanol 50:1. 0518 Yield: 7.1 g (20.9%) 0519 1H-NMR (200 MHz, CD3OD): ,45 (t, 3H); 1.65-1.80 (m, 2H); 1.80-2.00 (m, 4H); 2.05-2.20 (m, 2H); 2.60 (s, 3H); 3.65 (quin., 1H); 4.20 (quar., 2H); 7.10 (t, 1H); 7.15 (d, 1H); 7.50 (t, 1H); 7.70 (d, 1H).

EXAMPLE 26A

2-(2-Propoxyphenyl)-5-methyl-7-cyclopentyl-3H -imidazo5,1-f1,2,4-triazin-4-one 0520

0521 The preparation is carried out analogously to the procedure of example 16A using 8.33 g (45.0 mmol) of 2-cyclopentanoylaminopropionic acid (example 9A) and 9.65 g (45.0 mmol) of 2-propoxybenzamidine hydrochloride (example 15A). Purification is carried out by silica gel chromatography using the mobile phase dichloromethane/methanol 50:1. The product can be crystallized from ethyl acetate/petroleum ether. 0522 Yield: 1.82 g (11.5% of theory) white solid. 0523 1H-NMR (200 MHz, CDCl3): 1.15 (t, 3H), 1.70 (m, 2H), 1.95 (m, 4H), 2.15 (m, 2H), 2.65 (s, 3H), 3.65 (quin., 1H), 4.15 (t, 2H), 7.05 (d, 1H), 7.10 (t, 1H), 7.50 (td, 1H), 8.20 (dd, 1H).

EXAMPLE 27A

2-(2-Ethoxyphenyl)-5-ethyl-7-cyclopentyl)-3H -imidazo5,1-f1,2,4triazin-4-one 0524

0525 The preparation is carried out analogously to the procedure of example 16A using 8.77 g (44 mmol) of 2-cyclopentanoylaminobutyric acid (example 10A) and 8.83 g (44 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). The product is purified by silica gel chromatography using the mobile phase cyclohexane/ethyl acetate (6:4). 0526 Yield: 0.355 g (6.7%), white solid 0527 1H-NMR (CDCl3): 1.32 (t, 3H); 1.57 (t, 3H); 1.94 (m, 8H); 3.03 (quar, 2H)); 3.64 (quin, 1H); 4.27 (quar, 2H), 7.06 8d, 1H); 7.12 (t, 1H); 7.50 (t, 1H); 8.16 (dd, 1H); 9.91 (s, 1H).

EXAMPLE 28A

2-(2-Ethoxyphenyl)-5-methyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0528

0529 The preparation is carried out analogously to the procedure of example 16A using 14.9 g (70 mmol) of 2-cycloheptanoylaminopropionic acid (example 11A) and 14 g (70 mmol) of 2-ethoxybenzamidine hydrochloride (example 13). Purification of the product is carried out by silica gel chromatography using the mobile phase methylene chloride/methanol 10:1, then 50:1. 0530 Yield: 5.35 g (20.9%) 0531 1H-NMR (CD3OD): 1.45 (t, 3H); 1.6-2.0 (m, 10H); 2.1-2.2 (m, 2H); 2.7 (s, 3H); 3.65 (quin., 1H), 4.2 (quar., 2H); 7.1 (t, 1H); 7.2 (d, 1H); 7.6 (td, 1H); 7.75 (dd, 1H).

EXAMPLE 29A

2-(2-Ethoxyphenyl)-5-ethyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0532

0533 The preparation is carried out analogously to the procedure of example 16A using 1.02 g (4.5 mmol) of 2-cycloheptanoylaminobutyric acid (example 12A) and 0.98 g (4.9 mmol) of 2-ethoxybenzamidine hydrochloride (example 13A). Purification is carried out by silica gel chromatography using ethyl acetate/cyclohexane 1:1. 0534 Yield: 0.391 mg (14%) 0535 1H-NMR (200 MHz, D6-DMSO): 1.21 (t, 3H, CH3), 1.30 (t, 3H, CH3), 1.40-2.01 (m, 12H, CH2), 2.86 (g, 2H, CH2), 3.32 (m, 1H, CH), 4.10 (g, 2H, CH2), 7.05 (t, 1H), 7.15 (d, 1H), 7.51 (m, 2H), 11.50 (bs, 1H, NH).

EXAMPLE 30A

4-Benzyloxy-2-bromophenol 0536

0537 183 g of 4-benzyloxyphenol (914 mmol) are brominated according to the literature (J. C. S Perkin 1, 1981, 223). Following recrystallization from petroleum ether (with 5% ether), the product is obtained as a colorless solid. 0538 Yield: 189 g (74.1% of theory) 0539 MS (DCl, NH3): m/z (%)296/298 (M18) (100) 0540 1H-NMR (200 MHz, CDCl3): 4.96 (s, 2H); 5.19 (s, 1H); 6.70-6.95 (m, 2H); 7.10 (d, 1H); 7.39-7.45 (m, 5H).

EXAMPLE 31A

5-Benzyloxy-2-ethoxybrombenzene 0541

0542 186.18 of 4-benzyloxy-2-bromophenol (667 mmol) (example 30A) and potassium carbonate (276.56 g, 2 mol) are initially charged in 2 l of acetone. 74.7 ml of bromoethane (1 mol) are added dropwise, and the mixture is stirred at reflux for 24 h. The mixture is filtered off and concentrated. The resulting oily residue is dissolved in 1200 ml of ethanol. With vigorous stirring, the product is crystallized by slowly adding 900 ml of water. The product is filtered off with suction and the light-beige crystals are dried under high vacuum. 0543 Yield 178.9 g (95.1% of theory) 0544 MS (DCl, NH3): m/z (%)326/328 (M18) (100) 0545 1H-NMR (200 MHz, CDCl3): 1.45 (t, 3H); 4.05 (q, 2H); 4.98 (s, 2H), 6.79-6.90 (m, 2H); 7.18-7.46 (m, 6H).

EXAMPLE 32A

5-Benzyloxy-2-ethoxybenzonitrile 0546

0547 178.17 g of 5-benzyloxy-2-ethoxybromobenzene (580 mmol) (example 31A) are added to 57.14 g of copper cyanide (638 mmol), and the two components are mixed by shaking. Following addition of 65 ml of dry pyridine, the mixture is heated to 160 C. The mixture melts and forms a homogeneous solution. The solution is stirred at 160 C. for 6 h. After cooling to about 100 C., toluene is added and the mixture is stirred until the reaction mixture has cooled. The mixture is filtered through kieselguhr, and the kieselguhr is washed repeatedly with toluene. The filtrate is then washed with dilute ammonia solution until the aqueous phase is no longer blue. The mixture is washed with saturated sodium chloride solution, dried and concentrated. The resulting residue is recrystallized from 500 ml of ethanol, complete crystallization is achieved by addition of 100 ml of water. The crystals are filtered off with suction and washed repeatedly with petroleum ether. The brownish crystals are dried at 45 C. under reduced pressure. 0548 Yield 140.4 g (92.5% of theory) 0549 MS (DCl, NH3): m/z (%): 271 (M18) (100) 0550 1H-NMR (200 MHz, CDCl3): 1.45 (t, 3 H), 4.08 (q, 2H); 5.01 (s, 2H); 6.85-6.90 (1H); 7.10-7.18 (2H), 7.31-7.42 (m, 5H).

EXAMPLE 33A

3-Benzyloxy-6-ethoxybenzamidine hydrochloride 0551

0552 46.46 g of ammonium chloride (868.5 mol) are suspended in 650 ml of toluene, and the mixture is cooled to 0-5 C. Trimethylaluminum is added dropwise as a 2M solution in hexane (445 ml, 888.3 mmol), and the mixture is then stirred at room temperature unitil the evolution of gas has ceased. 5-Benzyloxy-2-ethoxybenzoitrile (100 g, 394.8 mmol) (example 32A) is added, and the mixture is stirred at 80 C. overnight. The cooled reaction mixture is, with ice-cooling, added to a suspension of 200 g of silica gel and 2 l of dichloromethane, and the mixture is stirred for 30 min. The mixture is filtered off with suction and the filter cake is washed with methanol. The organic phases are combined and concentrated. The resulting residue is triturated using a mixture of dichloromethane/methanol 9:1. filtered and concentrated using a rotary evaporator. The residue is then triturated with ether, and the colorless solid is filtered off with suction. 0553 Yield 59.4 g (49% of theory) 0554 1-NMR (300 MHz, D6-DMSO): 1.32 (t, 3H); 4.09 (q, 2H); 5.15 (s, 2H); 7.10-7.49 (m, 8H); 9.1-9.5 (m, 3).

EXAMPLE 34A

2-5-(benzyloxy)-2-ethoxyphenyl-7-cyclopentyl-5-methyl-3H-imidazo5,1-f1,2,4triazin-4-one 0555

0556 4.07 g of 2-cyclopentanoylaminopropionic acid (22 mmol) (example 9A) are initially charged in 22 ml of dry tetrahydrofuran and 5.3 ml of pyridine (66 mmol), 0.13 g of 4-DMAP are added and the mixture is is heated under reflux. Ethyl oxalyl chloride (6.7 ml, 44 mmol) is slowly added dropwise, and the resulting suspension is heated under reflux for two hours and then, after cooling, diluted with ethyl acetate and filtered, and the aqueous phase is ashed with 1N hydrochloric acid (2), saturated sodium bicarbonate solution (2) and saturated sodium chloride solution, dried over sodium sulfate and concentrated. After drying under high vacuum, a yellow oil is obtained which is, dissolved in 13 ml of ethanol, added to a solution which is prepared as follows: 0557 3.37 g of 3-benzyloxy-6-ethoxybenzamidine hydrochloride (11 mmol) (example 33A) are initially charged in 13 ml of ethanol, the mixture is cooled to 0 C. and 1.13 g of hydrazine hydrate (16.5 mmol) are added dropwise. The mixture is warmed to 40 C. and stirred for 10 min. 0558 After the ethanolic solution has been added, the mixture is stirred at 70 C. for 3.5 h. The mixture is concentrated and dried under high vacuum, and the yellow foam is dissolved in 100 ml of 1,2-dichloroethane, 2 ml of phosphorus oxychloride are added and the mixture is heated at reflux for 1.5 h. After cooling, the mixture is diluted with dichloromethane and washed with saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phase is dried with magnesium sulfate and concentrated. The dark residue is taken up in ethyl acetate, and after addition of petroleum ether precipitation occurs. The mixture is filtered off and the filtrate is then concentrated and the residue is cromatographed (cyclohexane/ethyl acetate 3:2). The product is recrystallized from ethyl acetate/petroleum ether. 0559 Yield 632 mg (12.9% of theory) 0560 MS (DCl, NH3): m/z (%)445 (MH) (100) 0561 1H-NMR (200 MHz, CDCl3): 1.55 (t, 3 H); 1.20-2.21 (m, 8H); 2.55 (s, 3H); 0562 3.61 (qui, 1H); 4.21 (q, 2H); 5.12 (s, 2H); 6.98 (d, 1H); 7.11 (dd, 1H); 7.32-7.50 (m, 5H); 7.78 (d, 1H); 10.10 (s, 1H).

EXAMPLE 35A 0563

0564 611 mg of the compound from example 34A (1.37 mmol) are suspended in 13 ml of ethanol. 13 ml of ether and a few drops of acetic acid are added (dissolution incomplete). Under an atmosphere of argon, 200 mg of 10% Pd/C are added to the suspension and the suspension is repeatedly flushed with hydrogen, then stirred vigorously under an H2 atmosphere (1 atm) for 2 h and finally filtered off through Celite. The filtrate is concentrated and dried under high vacuum and the residue is treated with ether/petroleum ether, filtered and dried under high vacuum. 0565 Yield 395 mg (81.5% of theory) 0566 MS (DCl, NH3): m/z (%)355 (MH) (100)

EXAMPLE 36A

Ethoxy-5-hydroxybenzonitrile 0567

0568 40.02 g of 5-benzyloxy-2-ethoxybenzonitrile (158 mmol) (example 32A) and 5% Pd/C (4.0 g) are initially charged in 1 l of methanol. The mixture is then hydrogenated under an atmosphere of hydrogen (1 atm) for about 4 h. The mixture is filtered through kieselguhr and evaporated and the crystalline residue is dried under reduced pressure. 0569 Yield 25.5 g (99.6% of theory) 0570 1H-NMR (200 MHz, CDCl3): 1.43 (t, 3H); 4.05 (q, 2H), 6.75-6.88 (m, 1H); 7.0-7.07 (m, 2H).

EXAMPLE 37A

5-Allyloxy-2-ethoxybenzonitrile 0571

0572 25 g of 2-ethoxy-5-hydroxybenzonitril (153.2 mmol) (example 36A) and potassium carbonate (63.52 g, 459.6 mmol) are initially charged in 750 ml of acetone. 19.9 ml of allyl bromide (229.8 mmol) are added, and the mixture is stirred under reflux overnight. The mixture is filtered off and concentrated giving a mobile orange oil. 0573 Yield 31 g (99.6% of theory) 0574 1H-NMR (200 MHz, D6-DMSO): 1.45 (t, 3H); 4.10 (q, 2H); 5.28-5.95 (m, 2H); 5.92-6.11, m 1H); 6.85-6.92 (m, 1H); 7.06-7.13 (m, 2H).

EXAMPLE 38A

3-Allyloxy-6-ethoxybenzamidine hydrochloride 0575

0576 17.95 g of ammonium chloride (335.56 mmol) are suspended in toluene and cooled to 0-5 C. Trimethylaluminum (2M solution in hexane, 172 ml, 343.2 mmol) are added dropwise, and the mixture is then stirred at room temperature until the evolution of gas has ceased. 5-Allyloxy-2-ethloxybenzonitrile (31 g, 152.5 mmol) (example 37A) is then added and the mixture is stirred at 80 C. overnight. The cooled mixture is then added to a mixture of 100 g of silica gel and 1 l of dichloromethane and stirred for 30 min. The mixture is filtered off with suction, the filter cake is washed twice with methanol and the filtrate is concentrated. The residue that is obtained is stirred with dichloromethane/methanol 9:1, filtered off and concentrated using a rotary evaporator. The residue consists of a red-brownish semicrystalline material. Using acetone, 10 g of a colorless solid are obtained after filtration. The mother liquor gives, after concentration using a rotary evaporator, 21 g of a viscous reddish oil which is dissolved in a little dichloromethane. The solution is seeded with a little product and allowed to stand overnight. Filtration with suction and washiing with a little acetone gives a further 6 g of solid. 0577 Yield 16 g (38.6% of theory) 0578 MS (DCI, NH3): m/z (%)221 (MCl) (100) 0579 1H-NMR (200 MHz, D6-DMSO): 1.32 (t, 3H); 4.08 (q, 2H); 4.60 (d, 2H); 5.35-5.97 (m, 2H); 5.94-6.15 (m, 1H); 7.13-7.22 (m, 3H); 9.2/9.35 (2 s, in total 4H).

EXAMPLE 39A

2-5-(Allyloxy)-2-ethoxyphenyl-7-cyclopentyl-5-methyl-3H-imidazo5,1-f1,2,4triazin-4-one 0580

0581 14.82 g of 2-cycloentanoylaminopropionic acid (example 9A) (80 mmol) are initially charged in 80 ml of dry tetrahydrofuran and 19.4 ml of pyridine (240 mmol), 0.49 g of 4-DMAP is added and the mixture is is heated under reflux. Ethyl oxalyl chloride (17.9 ml, 160 mmol) is slowly added dropwise, and the resulting suspension is heated under reflux for two hours. The mixturee is poured into ice-water and extracted three times with ethyl acetate. The extracts are dried and concentrated. The resulting oily residue is taken up in methanol, sodium bicarbonate is added and the mixture is boiled for 2.5 hours. After cooling, the mixture is filtered. The filtrate is added to a solution which was prepared as follows: 15 g of 3-allyloxy-6-ethoxybenzamidine hydrochloride (58.4 mmol) (example 38A) are initially charged in ethanol with ice-cooling. Over a period of 10 min, hydrazine hydrage (3.07 g, 61.3 mmol) is added dropwise, and the mixture is then stirted at room temperature for another 30 min. After 4 h at 70 C. the mixture is concentrated and the residue is taken up in 80 ml of 1,2-dichloroethane, mixed with 110 ml of phosphorus oxychloride and stirred under reflux for 1 h. The mixture is diluted with dichloromethane and neutralized using sodium bicarbonate. The mixture is once more washed with water and then dried and concentrated using a rotary evaporator. The crude product is pre-purified by silica gel flash chromatography using cyclohexane/ethyl acetate 1:1. The resulting oily residue is crystallized using ether. Another crystallization from cyclohexane/ethyl acetate 1:1 gives 3.34 g of a solid. The mother liquor is concentrated using a rotary evaporator and chromatographed using dichloromethane/acetone 95:5. This gives a further 2.9 g of product. 0582 Yield 6.24 g (27.1% of theory) 0583 MS (DCl, NH3): m/z (%)395 (MH) (100) 0584 1H-NMR (200 MHz, CDCl3): 1.56 (t, 3H); 1.69-2.21 (m, 8H); 2.65 (s, 3H); 3.65 (qui, 1H); 4.21 (q, 2H); 4.59 (dd, 2H) 5.30-5.51 (m, 2H); 5.99-6.28 (m, 1H); 6.95-7.09 (m, 2H); 7.75 (d, 1H); 10.10 (s, 1H).

EXAMPLE 40A

7-Cyclopentyl-2-2-ethoxy-5-(2-oxiranylmethoxy)phenyl-5-methyl-3H-imidazo5,1-f1,2,4triazin-4-one 0585

100

0586 4.26 g (10.8 mmol) of the compound from example 39A are dissolved in dichloromethane. Meta-chloroperbenzoic acid (7.64 g, technical grade, about 50%, 22.1 mmol) is added, and the mixture is stirred at room temperature for 7 h. The mixture is filtered, the filter cake is washed with dichloromethane and the filtrate is then washed with thiosulfite solution and 3 times with sodium bicarbonate solution, dried and concentrated. Flash chromatography using ethyl acetate/cyclohexane 6:4 gives 1.6 g of the starting material LMP 45-1 and 460 mg of product. 0587 Yield 460 mg (9.3% of theory) 0588 MS (DCl, NH3): m/z (%)411 (MH) (100) 0589 1H-NMR (200 MHz, CDCl3): 1.55 (t, 3H); 1.68-2.21 (m, 8H); 2.67 (s, 3H); 2.80 (dd, 1H); 2.95 (t, 1H); 3.38-3.41 (m, 1H); 3.67 (qui, 1H); 3.98 (dd, 1H); 4.12-4.32 (m, 3H); 6.92-7.13 (m, 2H); 7.78 (d, 1H).

EXAMPLE 41A

2-(2-Ethoxy-5-nitrophenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0590

101

0591 Using an ice-acetone bath, 48.6 ml of trifluoroacetic acid (TFA) and 12.1 ml of 70% strength nitric acid are cooled to 10 C, 3.0 g (8.86 mmol) of the compound from example 25A, dissolved in 7 ml of TFA are added dropwise, and the mixture is stirred at 0 C. for 20 hours. The reaction solution is stirred into 400 ml of ice-water and 200 ml of dichloromethane and neutralized using about 200 ml of saturated sodium bicarbonate solution. The aqueous phase is separated off and extracted 3 times with dichloromethane, and the combined organic phases are dried and concentrated. The residue is chromatographed on silica gel using toluene with added ethyl acetate in a gradient from 11 to 60%. 0592 Yield: 2.56 g (75.5% of theory) 0593 1H-NMR (200 MHz, DMSO): 1.37 (t, 3H), 1.58-2.00 (m, 8H), 2.49 (s, 3H), 3.50 (quin., 1H), 4.26 (quar, 2H), 7.39 (d, 1H), 8.39-8.47 (m, 2H), 11.77 (s, 1H).

EXAMPLE 42A

2-(5-Amino-2-ethoxyphenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0594

102

0595 In 86 ml of ethanol and 86 ml of tetrahydrofuran 2.56 g (6.68 mmol) of the compound from example 41A are stirred in the presence of 288 mg of Pd/C (10%) under an H2 atmosphere for 20 hours. The reaction solution is filtered with suction through 30 ml of silica gel, the filter cake is washed with ethanol/tetrahydrofuran and the filtrate is concentrated and dried under high vacuum overnight. The crude product is chromatographed on 500 ml of silica gel using toluene and ethyl acetate in a gradient system. 0596 Yield: 2.1 g (92.8% of theory) 0597 1H-NMR (200 MHz, DMSO): 1.25 (t, 3H), 1.58-2.0 (m, 8H), 2.48 (s, 3H), 3.41-3.58 (quin., 1H), 3.97 (quar, 2H), 4.92 (s, 2H), 6.69-6.90 (dd and d, 3H), 11.34 (s, 1H).

EXAMPLE 43A

2-(5-Nitro-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0598

103

0599 Analogously to the procedure of example 41A, 10.0 g (28.4 mmol) of the compound from example 26A are nitrated in 160 ml of trifluoroacetic acid and 40 ml of 70% strength nitric acid. The product is purified by silica gel chromatography using toluene and ethyl acetate in a gradient system. 0600 Yield: 5.15 g (45.7% of theory). 0601 1H-NMR (200 MHz, DMSO): 0.95 (t, 3H), 1.60-1.93 (m, 8H), 1.93-2.10 (m, 2H), 2.50 (s, 3H), 3.50 (quin., 1H), 4.17 (t, 2H), 7.40 (dd, 1H), 8.38-8.46 (m, 2H), 11.62 (s, 1H).

EXAMPLE 44A

2-(5-Amino-2-propoxyphenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0602

104

0603 Analogously to the procedure of example 42A 5.13 g (12.96 mmol) of the compound from example 43A are hydrogenated in tetrahydrofurane/ethanol (1:1) using 1.11 g of 10% Pd/C. The product is purified by silica gel chromatography using toluene and ethyl acetate as solvent gradient. 0604 Yield: 4.39 g (92.1% of theory). 0605 1H-NMR (200 MHz, DMSO): 0.91 (t, 3H), 1.57-2.00 (mm, 10H), 2.45 (s, 3H), 3.41-3.58 (quin., 1H), 3.88 (t, 2H), 4.93 (s, 2H), 6.72 (dd, 1H), 6.80 (d, 1H), 6.90 (d, 1H), 11.30 (s, 1H).

EXAMPLE 45A

2-(2-Ethoxy-3-nitrophenyl)-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0606

105

0607 Anagously to the procedure of example 41A, 1.5 g (4.80 mmol) of the compound from example 16A are nitrated in 27 ml of triflouroacetic acid and 6.6 ml of 70% strength nitric acid. 0608 Yield: 1.73 g (83.7% of theory). 0609 MS (ESI): 358 (MH), 0610 HPLC (analytic): 83.0% RT: 5.86 min, column: Nucleosil C18 (1254mm), solvent: 0.01 m H3PO4/acetonitrile (gradient), flow rate: 2 ml/min, 200-400nm, 0611 TLC: Rf0.43 (toluene:ethyl acetate2:8).

EXAMPLE 46A

2-(5-Amino-2-ethoxyphenyl)-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0612

106

0613 Analogously to the procedure of example 42A, 1.72 g (4.63 mmol) of the compound from example 45A are hydrogenated in 150 ml of ethanol using 200 mg of 10% Pd/C. 0614 Yield: 862 mg (56.9% of theory). 0615 1H-NMR (200 MHz, DMSO): 0.92 (t, 3H), 1.25 (t, 3H), 1.64-1.82 (hex, 2H), 2.50 (s, 3H), 2.82 (t, 2H), 3.90-4.01 (quar, 2H), 4.93 (s, 2H), 6.72 (dd, 1H), 6.80 (d, 1H), 6.90 (d, 1H), 11.35 (s, 1H); 0616 MS (DCI): 354 (MH). 0617 TLC: Rf0.33 (toluene:ethyl acetate 1:9).

EXAMPLE 47A

2-(2-Ethoxy-5-nitrophenyl)-5-methyl-7-(1-ethylpropyl)-3H-imidazo5,1-f1,2,4-tiazin-4-one 0618

107

0619 Analogously to the procedure of example 41A, 2.0 g (5.88 mmol) of the compound from example 18A are nitrated in 33 ml of trifluoroacetic acid and 8.3 ml of 70% strength nitric acid. The product is purified by chromatography on 1000 ml of silica gel using toluene and ethyl acetate in a gradient system. 0620 Yield: 1.84 g (81.3% of theory). 0621 1H-NMR (200 MHz, DMSO): 0.73 (t, 6H), 1.16 (t, 3H), 1.61-1.82 (m, 4H), 2.50 (s, 3H), 3.01-3.18 (m, 1H), 4.00 (quar, 2H), 7.49 (t, 1H), 7.91 (dd, 1H), 8.12 (dd, 1H), 12.92 (s, 1H).

EXAMPLE 48A

2-(5-Amino-2-ethoxyphenyl)-5-methyl-7-(1-ethylpropyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0622

108

0623 Analogously to the procedure of example 42A, 1.84 g (4.77 mmol) of the compound from example 47A are hydrogenated in 150 g of ethanol using 200 mg of 10% Pd/C. 0624 Yield: 1.57 g (92.4% of theory). 0625 1-NMR (200 MHz, DMSO): 0.75 (t, 6H), 1.24 (t, 3H), 1.66-1.84 (m, 4H), 2.50 (s, 3H), 3.11 (quin., 1H), 3.98 (quar, 2H), 4.93 (s, 2H), 6.71 (dd, 1H), 6.78 (d, 1H), 6.90 (d, 1H), 11.33 (s, 1H).

EXAMPLE 49A

2-(2-Ethoxy-5-nitrophenyl)-5-methyl-7-(2-ethylheptyl)-3H -imidazo5,1-f1,2,4-triazin-4-one 0626

109

0627 Analogously to the procedure of example 41A, 3.0 g (7.57 mmol) of the compound from example 23A are nitrated in 42.5 ml of trifluoroaceiic acid and 10.7 ml of 70% strength nitric acid. The product is purified by chromatography on 500 ml of silica gel using cyclohexane and ethyl acetate in a gradient system of from 95:5 to 40:60. 0628 Yield: 1.95 g (58.4% of theory). 0629 TLC: Rf0.65 (cyclohexane:ethyl acetate2:8).

EXAMPLE 50A

2-(5-Amino-2-ethoxyphenyl)-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0630

110

0631 Analogously to the procedure of example 42A, 1.95 g (4.42 mmol) of the compound from example 49A are hydrogenated in 120 g of ethanol using 200 mg of 10% Pd/C. Chromatography on 400 ml of silica gel using cyclohexane and ethyl acetate in a gradient system from 90:10 to 40:60 gives 1.26 g (69.4% of theory). 0632 1H-NMR (200 MHz, DMSO): 0.70-0.83 (m, 6H), 1.11-1.80 (m, 12H), 1.62-1.81 (m, 3H), 2.50 (s, 3H), 3.11-3.25 (quin., 1H), 3.97 (quar. 2H), 4.95 (s, 2H), 6.70-6.80 (m, 2H), 6.90 (d, 1H), 11.35 (s, 1H).

EXAMPLE 51A

2-(2-Ethoxy-5-chloromethylphenyl)-5-methyl-7-n-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0633

111

0634 A suspension of 1.50 g (4.8 mmol) of the compound from example 16A and 0.43 g (4.8 mmol) of paraformaldehyde in 25 ml of conc. HCl was heated at 120 C. for 2 h. The reaction mixture was poured into ice-water and extracted twice with ethyl acetate and then twice with CH2Cl2. The CH2Cl2 phase was dried over MgSO4 and concentrated under reduced pressure. This gave 1.22 g (70.4%) of the desired product. 0635 MS (DCl, NH3): m/z (%)361 MH (100) 0636 1H-NMR (200 MHz, D6-DMSO): 0.94 (t, 3H, CH3); 1.32 (t, 3H, CH3); 1.82 (g, 2H, CH2); 2.61 (s, 3H, CH3); 3.02 (t, 2H, CH2); 4.12 (g, 2H, CH2); 4.81 (s, 2H, CH2); 7.21 (d, 1H); 7.57-7.65 (m, 2H), 12.22 (bs, 1H, NH).

EXAMPLE 52A

2-(2-Ethoxy-5-chloromethylphenyl)-5-ethyl -7-n-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0637

112

0638 The preparation is carried out analogously to the procedure of example 51A using 1 g (3.06 mmol) of the compound from example 17A and 276 mg (3.06 mmol) of paraformaldehyde. 0639 Yield: 732 mg (59.6%)

EXAMPLE 53A

2-(2-Ethoxy-5-chloromethylphenyl)-5-methyl-7-(1,1-dimethylbutyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0640

113

0641 The preparation is carried out analogously to the procedure of example 51A using 1.5 g (4.2 mmol) of the compound from example 19A and 380 mg (4.2 mmol) of paraformaldehyde. 0642 Yield: 850 ng (49.8%) 0643 1H-NMR (200 MHz, CDCl3): 0.83 (t, 3H), 1.05-1.2 (m, 2H), 1.55 (s, 6H); 1.6 (t, 3H); 1.95-2.1 (m, 2H); 2.65 (s, 3H); 4.3 (quar., 2H); 4.62 (s, 2H); 7.05 (d, 1H); 7.53 (dd, 1H); 8.12 (d, 1H); 9.9 (s, 1H).

EXAMPLE 54A

2-(2-Ethoxy-5-chloromethylphenyl)-5-ethyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0644

114

0645 A suspension of 1.0 g (2.8 mmol) of the compound from example 27A and 256 mg (2.8 mmol) of paraformaldehyde in 20 ml of conc. HCl was heated at 120 C. for 2 h, giving a homogeneous solution. This solution was poured into ice-water and extracted twice with CH2Cl2, and the organic phase was dried over MgSO4 and concentrated under reduced pressure. Recrystallization from CH2Cl2/ether gave 314 mg (27.6%) of the desired product. Concentration of the mother liquor gave a further 806 mg (70.9%) of product. 0646 MS (EI): m/z (%)400 M (28) 0647 1H-NMR (200 MHz, CDCl3): 1.50 (t, 3H, CH3), 1.61 (t, 3H, CH3), 1.62-2.45 (m, 8H, 4CH2), 3.33 (t, 2H, CH2), 3.91 (m, 1H, CH), 4.28 (g, 2H, CH2O), 4.61 (s, 2H, CH2), 7.10 (d, 1H), 7.63 (dd, 1H), 8.15 (d, 1H), 10.51 (bs, 1H, NH).

EXAMPLE 55A

2-(2-Ethoxy-5-chloromethylphenyl)-5-methyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0648

115

0649 A suspension of 600 mg (1.6 mmol) of the compound from example 28A and 147 mg (1.6 mmol) of paraformaldehyde in 10 ml of conc. HCl was heated at 120 C. for a total of 4 h, with foaming reaction product being rinsed from the condenser. The mixture was poured into ice-water, the aqueous phase was extracted twice with ethyl acetate and the organic phase was dried over MgSO4. The organic phase was concentrated and the residue was then triturated with ether, and precipitated product was filtered off. This gave 558 mg of a 9:1mixture of product and starting material and another 189 mg (26.5%) of product by concentration of the mother liquor. 0650 MS (DCl, NH3): m/z (%)415 MH (100) 0651 1H-NMR (200 MHz, D6-DMSO): 1.30 (t, 3H, CH3), 1.45-2.15 (m, 12H, 6CH2), 2.60 (s, 3H, CH3), 3.45 (m, 1H, CH), 4.13 (g, 2H, CH2), 4.82 (s, 2H, CH2), 7.19 (dd, 1H), 7.62 (m, 2H), 12.18 (bs, 1H, NH).

EXAMPLE 56A

2-(2-Ethoxy-5-chloromethylphenyl)-5-ethyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0652

116

0653 Analogously to example 51A, 100 mg (0.26 mmol) of the compound from Example 29A in 2 ml of conc. HCl were heated with 23.7 mg (0.26 mmol) of paraformaldehyde at 120 C. for 2 h. Chromatographic purification (gradient: CH2Cl2:MeOH1 50:1) gave 60.8 mg (53.9%) of the desired product. 0654 MS (DCl, NH3): m/z (%)429 MH (100) 0655 1H-NMR (200 MHz, CDCl3): 1.32 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.60-2.08 (m, 12H, 6CH2), 3.02 (g, 2H, CH2), 3.44 (m, 1H, CH), 4.26 (g, 2H, CH2O), 4.63 (s, 2H, CH2), 7.06 (d, 1H), 7.54 (dd, 1H), 8.16 (d, 1H), 9.84 (bs, 1H, NH).

EXAMPLE 57A

2-5-(2-Bromoacetyl)-2-ethoxyphen)yl-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-o 0656

117

0657 A solution, cooled to 0 C., of 4 g (12.8 mmol) of the compound from example 16A in 80 ml of CH2Cl2 was initially admixed dropwise with 5.17 g (25.6 mmol) of bromoacetyl bromide and then, a little at a time, with 5.12 g (38.4 mmol) of AlCl3. The mixture was warmed to room temperature and then stirred for 30 min, and heated at reflux for 2 h. The reaction mixture was poured into ice-water and extracted once with CH2Cl2, and the organic phase was washed with sat. NaCl solution and dried over MgSO4. The residue obtained after concentration under reduced pressure was triturated with ether, and the product was filtered off with suction. This gave 6.2 g (>95%) of the desired product as a mixture of phenacyl bromide and phenacyl chloride. 0658 MS (ESl): m/z435 M (Br)H (100). 389 M (Cl)H (85) 0659 1H-NMR (200 MHz, D6-DMSO): 0.94 (t, 3H, CH3), 1.32 (t, 3H, CH3), 1.78 (m, 2H, CH2), 2.61 (s, 3H, CH3), 3.03 (t, 2H, CH2), 4.25 (g, 2H, CH2), 4.89 (s, 2H, CH2Br), 5.18 (s, 2H, CH2Cl), 7.34 (d, 1H), 8.07-8.25 (m, 2H), 12.40 (bs, 1H, NH)

EXAMPLE 58A

2-5-(2-Bromoacetyl)-2-ethoxyphenyl-5-ethyl-7-propyl-3H-imidazo5,1-f1,2,4triazin-4-one 0660

118

0661 A solution, cooled to 0 C., of 1 g (3.1 mmol) of the compound from example 17A in 80 ml of CH2Cl2 was admixed dropwise with 1.2 g (6.1 mmol) of bromoacetyl bromide and a little at a time with 1.2 g (9.1 mmol) of AlCl3. The reaction mixture was warmed to room temperature (30 min.) and then heated at reflux for 2 h and carefully poured into ice-water. Following extraction with CH2Cl2, drying over MgSO4 and concentration under reduced pressure, the residue was triturated with ether. This gave 1.33 g (33% pure according to LC-MS) of the desired product which was reacted further without further purification. 0662 MS (ESI): m/z (%)447 MH (100)

EXAMPLE 59A

2-5-(2-Bromoacetyl)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4triazin-4-one 0663

119

0664 The compound was obtained analogously to the compound from example 57A from 1 g (2.95 mmol) of the compound from example 25A and 1.19 g (5.9 mmol) of bromoacetyl bromide in the presence of 1.18 g (8.86 mmol) of aluminum trichloride. 0665 M.p.: 186 C. (ethyl acetate/ether) 0666 Yield: 770 mg (57%)

EXAMPLE 60A

2--(2-Bomoacetyl)-2-ethoxyphenyl-5-methyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4triazin-4-one 0667

120

0668 Analogously to example 57A, 1.36 g (3.7 mmol) of the compound from example 28A were reacted with 1.5 g (7.4 mmol) of bromoacetyl bromide and 1.48 g (1.1 mmol) of aluminum trichloride. Trituration with ether gave 1.2 g (66.3%) of the desired product. 0669 MS (DCl/NH3): m/z (%)487 MH (27%) 0670 1H-NMR (200 MHz, CDCl3): 1.63 (t, 3H, CH3), 1.75 (bs, 6H,), 1.89-2.42 (m, 6H), 2.94 (s, 3H, CH3), 3.75 (m, 1H, CH), 4.37 (s, 2H, CH2Br), 4.43 (g, 2H, CH2), 4.63 (s, 2H, CH2Cl), 7.23 (d, 1H), 8.25 (dd, 1H), 8.35 (d, 1H), 10.38 (bs, 1H, NH) 0671 Preparation of the active compounds

EXAMPLE 1

2-2-Ethoxy-5-(4-morpholinyl-sulfonamido)phenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0672

121

0673 250 mg (0.71 mmol) of the amino compound from example 42A are dissolved in 10 g of dichloromethane and cooled to 0 C., and 525 mg (2.83 mmol) of morpholine N-sulfonyl chloride, dissolved in 5 g of dichloromethane, are added under argon. The mixture is stirred without cooling for 30 minutes, and 336 mg (4.24 mmol) of pyridinie p.a. are then added dropwise. After a further 30 minutes, another 3.4 ml of pyridinie are added dropwise, and the mixture is stirred at room temperature overnight. The reaction solution is concentrated under reduced pressure at 40 C., whereupon the color of the solution changes to an intensive red. The mixture is stirred with 20 ml of ammonium chloride solution, with addition of a little sodium bicarbonate solution, for about 10 minutes and then extracted 4 times with ethyl acetate, and the extracts are dried and concentrated. The red oil is dissolved in 10 ml of toluene, applied to 100 ml of silica gel and chromatographed using toluene/ethyl acetate in a gradient system of from 80:20 to 20:80. The desired fractions are combined, concentrated and dried under reduced pressure. 0674 Yield: 211 mg (59.0% of theory). 0675 1H-NMR (200 MHz, DMSO): 1.31 (t, 3H), 1.55-2.10 (m, 8H), 2.48 (s, 3H), 3.10 (m, 4H), 3.41-3.51 (quin., 1H), 3.55 (m, 4H), 4.09 (quar, 2H), 7.10-7.26 (m, 2H), 7.38 (dd, 1H), 9.90 (s, 1H), 11.51 (s, 1H). 0676 HPLC (analytic): 99.9% RT: 3.62 min. column: Nucleosil C18 (1254 mm), mobile phase: 0.01 M H3PO4/acetonirile (gradient), flow rate: 2 ml/min, 200-400 nm. 0677 The following compounds are prepared analogously to the procedure of example 1 (example 2 to example 12):

EXAMPLE 2

2-2-Ethoxy-5-(4-methanesulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0678

122

0679 150 mg (0.42 mmol) of the compound from example 42A are reacted with 72.9 mg (0.64 mmol) of methanesulfonyl chloride. 0680 Yield: 172 mg (93.9% of theory). 0681 1H-NMR (200 MHz, DMSO): 1.30 (t, 3H), 1.59-2.03 (m, 8H), 2.47 (s, 3H), 2.97 (s, 3H), 3.47 (quin., 1H), 3.99-4.14 (m, 2H), 7.17 (d, 1H), 7.33-7.40 (dd, 2H).

EXAMPLE 3

2-2-Ethoxy-5-(4-isopropylsulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H -imidazo-5,1-f1,2,4-triazin-4-one 0682

123

0683 100 mg (0.28 mmol) of the compound from example 42A are reacted with 60.5 mg (0.42 mmol) of isopropylsulfonyl chloride. 0684 Yield: 112 mg (86.1% of theory). 0685 MS (DCI): 460 (MH). 0686 HPLC (analytic): 81.6% RT: 5.85 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 M H3PO4/acetonirile (gradient), flow rate: 2 ml/min, 200-400 nm, 0687 TLC: R0.55 (cyclohexane:ethyl acetate 2:8).

EXAMPLE 4

2-5-(4-N,N-Dimethylsulfamoylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-1,2,4-triazin-4-one 0688

124

0689 100 mg (0.28 mmol) of the compound from example 42A are stirred with 183 mg (1.27 mmol) of N,N-dimethylsulfamoyl chloride and 0.30 ml (3.71 mmol) of pyridine for 2 days. Yield: 90.8 mg (69.7% of theory). 0690 1H-NMR (300 MHz, DMSO): 1.30 (t, 3H), 1.59-2.07 (m, 8H), 2.47 (s, 3H), 2.70 (s, 6H), 3.45 (quin., 1H), 4.07 (quar, 2H), 7.10 (d, 1H), 7.32 (dd, 1H), 7.39 (d, 1H); 0691 MS (DCI): 461 (MH).

EXAMPLE 5

2-2-Ethoxy-5-(benzofurazane-4-sulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0692

125

0693 120 ml (0.34 mmol) of the compound from example 42A are reacted with 111 mg (0.509 mmol) of benzofurazane-4-sulfonyl chloride and 0.17 ml (2.10 mmol) of pyridine. Yield: 109 mg (60.1% of theory). 0694 1H-NMR (200 MHz, DMSO): 1.10 (t, 3H), 1.63-2.05 (m, 8H), 2.45 (s, 3H), 3.39 (quin., 1H), 4.00 (quar, 2H), 7.04 (d, 1H), 7.12-7.28 (m, 2H), 7.70 (dd, 1H), 8.09 (d, 1H), 8.38 (d, 1H), 10.84 (s,1H), 11.39 (s, 1H); 0695 MS (DCI): 536 (MH).

EXAMPLE 6

2-5-(4-n-Butoxybenzenesulfonylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0696

126

0697 150 mg (0.424 mmol) of the compound from example 42A are reacted with 186 mg (0.747 mmol) of 4-(n-butoxy)-benzenesulfonyl chloride and 0.34 g (4.30 mmol) of pyridine in 6 ml of tetrahydrofuran. 0698 Yield: 99.5 mg (41.4% of theory). 0699 1H-NMR (300 MHz, DMSO): 0.92 (t, 3H), 1.25 (t, 3H), 1.40 (hex., 2H), 1.60-2.05 (m, 10H), 2.45 (s, 3H), 3.43 (quin., 1H), 4.00 (m, 4H), 7.03 (dd, 3H), 7.15-7.28 (m, 2H), 7.67 (d, 2H), 10.03 (s, 1H), 11.43 (s, 1H); 0700 MS (ESI): 566 (MH).

EXAMPLE 7

2-5-Bis(N,N-Butoxybenzenesulfonyl)amino-2-ethoxy-phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0701

127

0702 In example 6, 63.3 mg (19.2% of theory) of the bis derivative are isolated as a by-product. 0703 1H-NMR (200 MHz, DMSO): 0.95 (t, 6H), 1.30-1.52 (m, 8H), 1.65-2.03 (m, 1H), 2.47 (s, 3H), 3.47 (quin., 1H), 4.04-4.21 (m, 6H), 7.06-7.25 (m, 7H), 7.72 (d, 4H), 11.54 (s, 1H); 0704 MS (ESI): 778 (MH).

EXAMPLE 8

2-2-Ethoxy-5-(1-methylimidazole-4-sulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0705

128

0706 150 mg (0.424 mmol) of the compound from example 42A are reacted with 307 mg (1.70 mmol) of 1-methylimidazole-4-sulfonyl chloride and 0.34 ml (4.24 mmol) of pyridinie in 5 ml of tetrahydrofuran. 0707 Yield: 155 mg (73.8% of theory). 0708 1H NMR (200 MHz, DMSO): 1.27 (t, 3H), 1.55-2.10 (m, 8H), 2.47 (s, 3H), 3.47 (quint., 1H), 3.65 (s, 3H), 4.02 (quar, 2H), 7.05 (d, 1H), 7.30 (dd, 2H), 7.75 (dd, 2H), 10.13 (s, 1H), 11.47 (s, 1H); 0709 MS (ESI): 498 (MH).

EXAMPLE 9

2-2-Ethoxy-5-(4-methylpiperazin-1-yl-sulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo-5,1-f1,2,4-triazin-4-one 0710

129

0711 120 mg (0.34 mmol) of the compound from example 42A are reacted with 319 mg (1.36 mmol) of 4-methyl-1-piperazinesulfonyl chloride in 8 ml (98.9 mmol) of pyridine overnight. 0712 Yield: 25.8 mg (14.7% oft heory). 0713 1H NMR (200 MHz, CDCL3): 1.56 (t, 3H), 1.65-2.20 (m, 9H), 2.27 (s, 3H), 2.42 (t, 4H), 2.62 (s, 3H), 3.30 (t, 4H), 3.62 (quin., 1H),4.22 (quar, 2H), 7.02 (d, 1H), 7.40 (dd, 1H), 7.97 (d, 1H), 10.00 (s, 1H); 0714 MS (ESI): 516 (MH).

EXAMPLE 10

2-5-(6-Chloroimidazo(2,1-b)thiazole-5-sulfonylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0715

130

0716 149 mg (0.42 mmol) of the compound from example 42A are reacted with 328 mg (1.28 mmol) of 6-chloroimidazo(2,1-b)thiazole-5-sulfonylchloride and 0.68 ml (8.41 mmol) of pyridine in tetrahydrofuran, initially at room temperature and then a 50 C. 0717 Yield: 9.6 mg (4.0% of theory). 0718 MS (ESI): 574 (MH). 0719 TLC: Rf0.54 (toluene:ethyl acetate2:8).

EXAMPLE 11

2-5-(4-Carboxybenzenesulfonylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0720

131

0721 100 mg (0.283 mmol) of the compound from example 42A are reacted with 187 mg (0.849 mmol) of 4-chlorosulfonylbenzoic acid and 224 mg (2.83 mmol) of pyridine in 6 ml of tetrahydrofuran overnight. 0722 Yield: 131 mg (85.9% of theory). 0723 MS (DCI/NH3): 538 (MH). 0724 HPLC (analytical): 89.6% RT: 5.66 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonirile (gradient), flow rate: 2 ml/min, 200-400 nm; 0725 TLC: Rf0.30 (ethyl acetate:methanol2:8).

EXAMPLE 12

2-5-(3-Carboxybenzenesulfonylamido)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imnidazo5,1-f1,2,4-triazin-4-one 0726

132

0727 100 mg (0.283 mmol) of the compound from example 42A are reacted with 187 mg (0.849 mmol) of 3-chlorosulfonylbenzoic acid and 224 mg (2.829 mmol) of pyridine in 6 ml of tetrahydrofuran overnight. 0728 Yield: 110 mg (72.0% of theory). 0729 1H-NMR (200 MHz, DMSO): 1.25 (t, 3H), 1.57-2.08 (m, 8H), 2.47 (s, 3H), 3.37 (m, 1H), 4.02 (quar, 2H), 7.09 (d, 1H), 7.17 (m, 2H), 7.70 (t, 1H), 7.92 (d, 1H), 8.15 (d, 1H), 8.31 (s, 1H), 10.30 (s, 1H), 11.42 (s, 1H), 13.52 (s, 1H); 0730 MS (DCI/NH3): 538 (MH).

EXAMPLE 13

2-(5-Methylsulfonylamino-2-propoxyphenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0731

133

0732 With ice-cooling, 646 mg (8.16 mmol) of pyridine and, after 15 minutes of stirring, 140 mg (1.23 mmol) of methanesulfonyl chloride (dropwise) are added to 300 mg (0.816 mmol) of the amino compound from example 44A in 10 ml of dichloromethane. After 2.5 hours of stirring at room temperature, 60 ml of dichloromethane, 30 ml of water and 20 ml of NH4Cl solution are stirred into the reaction mixture, the organic phase is separated off, the aqueous phase is reextracted with dichloromethane and the organic phases are combined, washed with saturated NaCl solution, dried and concentrated. Chromatography on 100 ml of silica gel using dichloromethane and methanol as a solvent gradient gives 315 mg (86.7% of theory). 0733 1H-NMR (200 MHz, DMSO): 0.91 (t, 3H), 1.58-2.09 (m, 10H), 2.44 (s, 3H), 2.98 (s, 3H), 3.49 (quin., 1H), 4.00 (t, 2H), 7.18 (d, 1H), 7.35 (dd, 2H), 9.62 (s, 1H), 11.50 (s, 1H); 0734 MS (ESI): 446 (MH), 0735 TLC: Rf0.30 (toluene:ethyl acetate6:4). 0736 The following compounds (example 14 to example 24) are prepared analogously to the procedure of example 19:

EXAMPLE 14

2-2-Propoxy-5-(3-trifluoromethlylbenzenesulfonamido)phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0737

134

0738 120 mg (0.327 mmol) of the compound from example 44A are reacted with 120 mg (0.49 mmol) of 3-(trifluoromethyl)benzenesulfonyl chloride and 0.28 ml (3.27 mmol) of pyridine in 5 ml of tetrahydrofuran overnight. 0739 Yield: 128 mg (68.3% of theory). 0740 1H-NMR (400 MHz, DMSO): 0.90 (t, 3H), 1.65 (m, 4H), 1.80 (m, 4H), 1.95 (m, 2H), 2.45 (s, 3H), 3.43 (quin., 1H), 3.93 (t, 2H), 7.06 (d, 1H), 7.12-7.26 (m, 2H), 7.82 (t, 1H), 7.98 (t, 1H), 8.03 (d, 2H), 10.36 (s, 1H), 11.37 (s, 1H); 0741 MS (DCI/NH3): 576 (MH).

EXAMPLE 15

2-5-(3-Chloropropanesulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H -imidazo5,1-f1,2,4-triazin-4-one 0742

135

0743 368 mg (1.0 mmol) of the compound from example 44A are reacted with 266 mg (1.5 mmol) of 3-chloropropanesulfonyl chloride and 0.81 ml (10.0 mmol) of pyridine in 12 ml of dichloromethane for 3 hours. 0744 Yield: 508 mg (85.7% of theory). 0745 1H-NMR (200 MHz, DMSO): 0.92 (t, 3H), 1.55-2.22 (m, 12H), 2.47 (s, 3H), 3.20 (t, 2H), 3.47 (quin., 1H), 3.75 (t, 2H), 3.97 (t, 2H), 7.18 (d, 1H), 7.39 (dd, 2H), 9.80 (s, 1H), 11.47 (s, 1H); 0746 MS (ESI): 508 (MH).

EXAMPLE 16

2-5-(p-Nitrobenzenesulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imimdazo5,1-f1,2,4-triazin-4-one 0747

136

0748 150 mg (0.408 mmol) of the compound from example 44A are reacted with 136 mg (0.612 mmol) of p-nitrobenzenesulfonyl chloride and 0.33 ml (4.08 mmol) of pyridine in 6 ml of tetrahydrofuran ovenight. 0749 Yield: 205 mg (91.1% of theory). 0750 1H NMR (300 MHz, DMSO): 0.90 (t, 3H), 1.57-2.02 (m, 10H), 2.45 (s, 3H), 3.40 (quin., 1H), 3.92 (t, 2H), 7.08 (d, 1H), 7.23 (t, 2H), 7.97 (d, 2H), 8.38 (d, 2H), 10.52 (s, 1H), 11.43 (s, 1H); 0751 MS (DCI/NH3): 553 (MH).

EXAMPLE 17

2-5-(Quinoline-8-sulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0752

137

0753 150 mg (0.408 mmol) of the compound from example 44A are reacted with 221 mg (0.96 mmol) of quinoline-8-sulfonyl chloride and 0.33 ml (4.08 mmol) of pyridine in 8 ml of tetrahydrofuran overnight. 0754 Yield: 180 mg (79.0% of theory). 0755 1H NMR (200 MHz, DMSO): 0.85 (t, 3H), 1.50-2.03 (m, 10H), 2.43 (s, 3H), 3.30 (m, 1H), 3.82 (t, 2H), 6.93 (d, 1H), 7.17 (m, 2H), 7.63-7.77 (m, 2H), 8.30 (m, 2H), 8.53 (dd, 1H), 9.17 (dd, 1H), 9.90-10.17 (bs, 1H), 11.17-11.43 (bs, 1H); 0756 MS: 559 (MH).

EXAMPLE 18

2-5-(4-tert-Butylbenzenesulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0757

138

0758 150 mg (0.408 mmol) of the compound from example 44A are reacted with 143 mg (0.612 mmol) of 4-tert-butylbenzenesulfonyl chloride and 0.33 ml (4.08 mmol) of pyridine in 8 ml of tetrahydrofuran for 1 hour. 0759 Yield: 203 mg (88.0% of theory). 0760 1H NMR (200 MHz, DMSO): 0.91 (t, 3H), 1.25 (s, 9H), 1.55-2.12 (m, 10H), 2.47 (s, 3H), 3.45 (quint., 1H), 3.93 (t, 2H), 7.07 (d, 1H), 7.20-7.30 (m, 2H), 7.57 (d, 2H), 7.70 (d, 2H), 10.25 (bs, 1H), 1.41 (bs, 1H); 0761 MS (DCI/NH3): 564 (MH).

EXAMPLE 19

2-5-(4-Methylpiperazin-1-yl-sulfonylamino)-2-propoxy-phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0762

139

0763 150 mg (0.408 mmol) of the compound from example 44A are treated with 576 mg (2.45 mmol) of 4-methyl-1-piperazinesulfonyl chloride in 6.6 ml (81.6 mmol) of pyridine for 3.5 hours. 0764 Yield: 106 mg (48.8% of theory). 0765 1H NMR (300 MHz, DMSO): 0.93 (t, 3H), 1.53-2.10 (m, 10H), 2.17 (s, 3H), 2.27 (s, 4H), 2.47 (s, 3H), 3.08 (s, 4H), 3.48 (quin., 1H), 3.97 (t, 2H), 7.13 (d, 1H), 7.32 (dd, 1H), 7.40 (d, 1H), 9.87 (s, 1H), 11.48 (s, 1H); 0766 MS (ESI): 530 (MH).

EXAMPLE 20

2-5-(4-Methylpiperazin-1-yl-sulfonylamino)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one dihydrochloride 0767

140

0768 62.9 mg (0.119 mmol) of the compound from example 19 are dissolved in 5 ml of dichloromethane and filtered through a small glass frit, and the filter residue is washed with 1 ml of dichloromethane. 1 ml of 1M HCl in ether is added dropwise to the filtrate, giving a somewhat sticky precipitate which crystallizes after further stirring and scratching. After 15 minutes of stirring in 15 ml of ether, the crystalline product is filtered off with suction, washed with ether and dried under high vacuum. 0769 Yield: 36.3 mg (50.2% of theory). 0770 MS (ESI): 530 (MH) for the free base. 0771 HPLC (analytic): 97.4% RT: 4.70 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 21

2-5-(2,5-Dichlorothiophene-3-sulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0772

141

0773 150 mg (0.408 mmol) of the compound from example 44A are reacted with 308 mg (1.224 mmol) of 2,5-dichlorothiophene-3-sulfonyl chloride and 0.33 ml (4.08 mmol) of pyridine in tetrahydrofuran for 4 hours. 0774 Yield: 66.1 mg (27.8% of theory). 0775 1H NMR (300 MHz, DMSO): 0.93 (t, 3H), 1.58-2.10 (m, 10H), 2.45 (s, 3H), 3.47 (quin., 1H), 3.97 (t, 2H), 7.12 (d, 1H), 7.22-7.31 (m, 3H), 10.57 (s, 1H), 11.48 (s, 1H); 0776 MS (ESI): 582 (MH).

EXAMPLE 22

2-2-Propoxy-5-(4,4,4-trifluoro-1-butanesulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0777

142

0778 150 mg (0.408 mmol) of the compound from example 44A are reacted with 183 mg (0.87 mmol) of 4,4,4-trifluoro-1-butanesulfonyl chloride and 484 mg (6.12 mmol) of pyridine in 8 ml of tetrahydrofuran for 3 hours. 0779 Yield: 33.5 mg (15.2% of theory). 0780 MS (DCI/NH3): 542 (MH) 0781 HPLC (analytic): 97.5% RT: 6.99 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm; 0782 TLC: Rf0.64 (toluene:ethyl acetate2:8).

EXAMPLE 23

2-5-(3-Cyanobenzenesulfonamido)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0783

143

0784 200 mg (0.566 mmol) of the compound from example 44A are reaccted with 342 mg (1.70 mmol) of 3-cyanobenzenesulfonyl chloride and 0.46 ml (5.66 mmol) of pyridine in 15 ml of tetrahydrofuran overnight. 0785 Yield: 58.8 mg (19.5% of theory). 0786 1H-NMR (200 MHz, DMSO): 0.90 (t, 3H), 1.55-2.08 (m, 10H), 2.45 (s, 3H), 3.42 (quin., 1H), 3.93 (t, 2H), 7.06-7.28 (m, 3H), 7.82 (quar, 1H), 8.00 (d, 1H), 8.12 (d, 2H), 10.38 (s, 1H), 11.42 (s, 1H); 0787 MS (ESI): 533 (MH).

EXAMPLE 24

2-5-(-Morpholinopropanesulfonylamino)-2-propoxy-phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0788

144

0789 100 mg (0.272 mmol) of the compound from example 44A are reacted with 250 mg (1.09 mmol) of -morphokinopropanesulfonyl chloride and 0.22 ml (2.73 mmol) of pyridine in 5 ml of tetrahydrofuran overnight. 0790 Yield: 137 mg (90.0% of theory). 0791 MS (DCI/NH3): 559 (MH), 0792 HPLC (analytic): 90.0% RT: 4.68 min, column: Nuceosil C18 (1254 mm), mobile phase: 0.01 H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm; 0793 TLC: Rf0.28 (ethyl acetate:methanol9:1).

EXAMPLE 25

2-5-(N,N-Bismethylsulfonyl)amino-2-propoxy-phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0794

145

0795 37.9 mg (0.38 mmol) of triethylamine and 42.9 mg (0.38 mmol) of methanesulfonyl chloride are added successively to 55.1 mg (0.15 mmol) of the amino compound from example 44A in 5 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 1 hour. The reaction solution is concentrated, the residue is partitioned between water and ethyl acetate and the organic phase is separated off, dried and concentrated. The residue is chromatographed on 30 ml of silica gel using dichloromethane and methanol in a gradient system. 0796 Yield: 51.7 mg (77.4% of theory). 0797 MS (ESI): 524 (MH), 0798 TLC: Rf0.52 (toluene:ethyl acetate6:4). 0799 5.8 mg (8.7% of theory) of the monomesyl derivativeexample 13 are isolated as a by-product. 0800 The following compounds (example 26 to example 35) are prepared analogously to the procedure of example 25:

EXAMPLE 26

2-5-(N,N-Bisisopropylsulfonyl)amino-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0801

146

0802 150 mg (0.408 mmol) of the compound from example 44A are reacted with 116 mg (0.816 mmol) of 2-propanesulfonyl chloride and 0.12 ml (0.857 mmol) of triethylamine in 15 ml of tetrahydrofuran for 1 hour. 0803 Yield: 41.0 mg (17.4% of theory). 0804 MS (ESI): 580 (MH), 0805 HPLC (analytic): 98.9% RT: 7.91 min, column: Kromasil (1252 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm; 0806 TLC: Rf0.40 (toluene:ethlyl acetate1:1).

EXAMPLE 27

2-(5-Isopropylsulfonylamino-2-propoxyphenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0807

147

0808 In examnple 26, 11.4 mg (5.90% of theory) of the monoisopropyl derivative are isolated as a by-product. 0809 MS (ESI): 474 (MH), 0810 TLC: Rf0.35 (toluene:ethyl acetate1:1).

EXAMPLE 28

2-2-Propoxy-5-2-(2,2,2-trifluoro-1-trifluoromethylethoxy)ethanesulfonylamino-phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0811

148

0812 150 mg (0.408 mmol) of the compound from example 44A are reacted with 180 mg (0.612 mmol) of 2-(2,2,2-trifluoro-1-trifluoromethylethoxy)ethanesulfonyl chloride and 0.085 ml (0.612 mmol) of triethylamine for 1 hour. 0813 Yield: 77.0.mg (30.2% of theory). 0814 1H-NMR (200 MHz, DMSO): 0.93 (t,3H), 1.53-2.07 (m, 10H), 2.47 (s, 3H), 3.42 (quin., 1H), 3.97 (t, 2H), 4.20 (t, 2H), 5.60 (quin., 1H), 7.17 (d, 1H), 7.37 (dd, 2H), 9.88 (bs, 1H), 11.50 (bs, 1H); 0815 MS (DCI/NH3): 626 (MH).

EXAMPLE 29

2-(2-Propoxy-5-vinylsulfonylaminophenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0816

149

0817 During the preparation of example 28, the vinylsulfonylamido derivative is formed as a by-product. 0818 Yield: 64.5 mg (25.3% of theory). 0819 1H-NMR (200 MHz, DMSO): 0.92 (t, 3H), 1.52-2.08 (m, 10H), 2.43 (s, 3H), 3.47 (quint., 1H), 3.97 (t, 2H), 6.03 (dd, 2H), 6.79 (dd, 1H), 7.13 (d, 1H), 7.27 (d, 1H), 7.37 (m, 1H), 9.97 (bs, 1H), 11.45 (bs, 1H); 0820 MS (DCI/NH3): 458 (MH).

EXAMPLE 30

2-2-Propoxy-5-(4,4,5,5,5-pentafluoropentanesulfonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0821

150

0822 150 mg (0.408 mmol) of the compound from example 44A are treated with 160 mg (0.612 mmol) of 4,4,5,5,5-pentafluoropentanesulfonyl chloride and 62 mg (0.612 mmol) of triethylamine in 8 ml of tetrahydrofuran for 1 hour. 0823 Yield: 171 mg (70.9% of theory). 0824 1H-NMR (200 MHz, DMSO): 0.93 (t, 3H), 1.53-2.09 (m, 12H), 2.23-2.42 (m, 2H), 2.47 (s, 3H), 3.22 (t, 2H), 3.47 (quin., 1H), 3.97 (t, 2H), 7.17 (d, 1H), 7.37 (dd, 2H), 9.83 (s, 1H), 11.48 (s, 1H); 0825 MS (DCI/NH3): 592 (MH).

EXAMPLE 31

2-5-Bis(N,N-4,4,5,5,5-pentafluoropentanesulfonyl)amino-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0826

151

0827 In example 30, 10.2 mg (4.20% of theory) of the bis derivative are isolated as a by-product. 0828 MS (ESI): 816 (MH), 0829 TLC: Rf0.74 (toluene:ethyl acetate:formic acid2:7.5:0.5).

EXAMPLE 32

2-5-Bis(N,N-4,4,4-trifluoro-1-butanesulfonyl)amino-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0830

152

0831 150 mg (0.408 mmol) of the compound from example 44A are reacted with 529 mg (2.512 mmol) of 4,4,4-trifluoro-1-butanesulfonyl chloride and 0.49 ml (3.516 mmol) of triethylamine in 12 ml of tetrahydrofuran for 5 hours. 0832 Yield: 194 mg (66.8% of theory). 0833 1H-NMR (200 MHz, DMSO): 0.95 (t, 3H), 1.53-2.15 (m, 18H), 2.47 (s, 3H), 3.50 (quin., 1H), 3.80 (t, 4H), 4.08 (t, 2H), 7.28 (d, 1H), 7.62 (m, 2H), 11.62 (s, 1H); 0834 MS (ESI): 716 (MH).

EXAMPLE 33

2-5-Bis(N,N-3-trifluoromethylbenzenesulfonyl)amino-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0835

153

0836 150 mg (0.408 mmol) of the compound from example 44A are reacted with 399 mg (1.632 mmol) of 3-(trifluoromethyl)benzenesulfonyl chloride and 0.239 ml (1.714 mmol) of pyridine in 8 ml of tetrahydrofuran for 3 hours. 0837 Yield: 169 mg (52.8% d.Th.). 0838 1H-NMR (200 MHz, DMSO): 0.95 (t, 3H), 1.57-2.00 (m, 10H), 2.47 (s, 3H), 3.42 (m, 1H), 4.07 (t, 2H), 7.22 (s, 1H), 7.27 (s, 2H), 7.97 (t, 2H), 8.07 (s, 2H), 8.17 (d, 2H), 8.27 (d, 2H), 11.57 (s, 1H); 0839 MS (ESI): 784 (MH).

EXAMPLE 34

2-(2-Propoxy-5-propanesulfonylaminophenyl)-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0840

154

0841 150 mg (0.408 mmol) of the compound from example 44A are treated with 116 mg (0.816 mmol) of 1-propanesulfonyl chloride and 87 mg (0.816 mmol) of triethylamine in 15 ml of tetrahydrofuran for 1 hour. 0842 Yield: 72.6 mg (37.6% of theory). 0843 1H-NMR (300 MHz, DMSO): 0.94 (quar, 6H), 1.58-2.05 (m, 12H), 2.48 (s, 3H), 3.02 (m, 2H), 3.45 (quin., 1H), 3.98 (t, 2H), 7.13 (d, 1H), 7.34 (dd, 1H), 7.40 (d, 1H), 9.63 (s, 1H), 11.40 (s, 1H); 0844 MS (ESI): 474 (MH).

EXAMPLE 35

2-5-Bis(N,N-propanesulfonyl)amino-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0845

155

0846 In example 34, 73.3 mg (31.0% of theory) of the bis derivative are isolated as a by-product. 0847 1H-NMR (300 MHz, DMSO): 1.00 (tt, 9H), 1.59-2.04 (m, 14H), 2.48 (s, 3H), 3.48 (quin., 1H), 3.64 (t, 4H), 4.07 (t, 2H), 7.23 (d, 1H), 7.62 (m, 2H), 11.56 (s, 1H); 0848 MS (ESI): 580 (MH).

EXAMPLE 36

2-2-Ethoxy-5-(4-ethylpiperazin-1-yl-sulfonylamino)phenyl-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0849

156

0850 Under argon, 400 mg (1.22 mmol) of the amino compound from example 46A in 19.3 g (244 mmol) of pyridine are reacted with 1.22 g (4.89 mmol) of 4-ethyl-1-piperazinesulfonyl chloride hydrochloride at room temperature for 16 hours. The solution is then concentrated and the residue is taken up in toluene and re-concentrated. The residue is then partitioned between 170 ml of dichloromethane, 10 ml of NaHCO3 solution and 5 ml of water, the organic layer is separated off, the aqueous layer is washed twice with dichloromethane and the organic phase is dried and concentrated. Purification of the crude product is carried out byt chromatography on 140 ml of silica gel using ethyl acetate with acetone added in increasing proportions of from 11% to 43%. 0851 Yield: 394 mg (64.0% of theory). 0852 TLC: Rf0.48 (acetone). 0853 Formation of the hydrochloride: 383 mg (0.76 mmol) of the free base are dissolved in 2 ml of dichloromethane and stirred with 2 ml of 1 M HCl in ether. 15 ml of ether are then added and the mixture is stirred for 20 minutes, resulting in the precipitation of a solid material which is filtered off with suction, washed with 15 ml of ether and dried under reduced pressure. 0854 Yield: 235 mg (51.1% of theory). 0855 1H-NMR (200 MHz, DMSO): 0.95 (t, 3H), 1.24 (m, 6H), 1.80 (hex, 2H), 2.58 (s, 3H), 2.83-3.90 (mm, 12H), 4.08 (quar., 2H), 7.18 (d, 1H), 7.39 (d, 1H) 7.42 (s, 1H), 10.15 (s, 1H), 12.02 (s, 1H); 0856 MS (ESI): 504 (MH).

EXAMPLE 37

2-2-Ethoxy-5-(morpholinylsulfonamido)phenyl-5-methyl-7-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0857

157

0858 Analogously to the procedure of example 36, 150 mg (0.458 mmol) of the amino compound from example 46A are reacted with 680 mg (3.67 mmol) of morpholine N-sulfonyl chloride in 7.4 ml of pyridine under argon at 40 C. for 8 hours. 0859 Yied: 128 mg (58.5% of theory). 0860 MS (DCI/NH3): 477 (MH), 0861 HPLC (analytic): 92.8% RT: 5.13 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 38

2-2-Ethoxy-5-(4-ethylpiperazin-1-yl-sulfonylamino)phenyl-7-(1-ethylpropyl)-5-methyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0862

158

0863 The preparation was carried out analogously to the procedure of example 36 using 150 mg (0.422 mmol) of the amino compound of example 48A and 421 mg (1.69 mmol) of 4-ethylpiperazinesulfonyl chloride hydrochloride in 6.81 ml of pyridine. The crude product is purified by chromatography on 100 ml of silica oel using ethyl acetate and acetone as mobile phase in a giradient system of from 9:1 to 1:1. 0864 Yield: 22.4 mg (10.0% of theory). 0865 MS (DCI/NH3): 532 (MH). 0866 HPLC (analytic): 93.5% RT: 4.64 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 39

2-2-Ethoxy-5-(4-ethylpiperazin-1-yl-sulfonylamino)phenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0867

159

0868 The preparation is carried out analogously to the procedure of example 36 using 120 mg (0.292 mmol) of the amino compound from example 50A and 581 mg (2.33 mmol) of 4-ethyl-piperazinesulfonyl chloride hydrochloride in 4.71 ml of pyridinie at room lemperature. The crude product is purified by chromatography on 40 ml of silica gel using ethyl acetate and methanol as mobile phase. 0869 Yield: 63.6 mg (37.1% of theory). 0870 MS (ESI): 588 (MH). 0871 TLC: Rf0.57 (ethyl acetate:methanol8:2).

EXAMPLE 40

2-5-(4-Carboxybenzenesulfonlamino)-2-ethoxyphenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0872

160

0873 Analogously to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 80.4 mg, (0.364 mmol) of 4-chlorosulfonylbenzoic acid and 0.10 ml (1.22 mmol) of pyridine in 6 ml of tetrahydrofuran overnight. The product is purified by chromatography on 40 ml of silica gel using ethyl acetate and methanol as mobile phase in a gradient system of from 95:5 to 8:2. 0874 Yield: 65.4 mg (90.4% of theory). 0875 MS (DCI/NH3): 596 (MH), 0876 HPLC (analytic): 90.4% RT: 7.08 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 41

2-2-Ethoxy-5-(-Morpholinopropanesulfonylamino)phenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0877

161

0878 Analogously to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 111 mg (0.486 mmol) of -morpholinopropanesulfonyl chloride and 0.10 ml (1.22 mmol) of pyridine in 6 ml of tetrahydrofuran overnight. Purification of the product on silica oel using ethyl acetate and methanol as mobile phase gives 66.3 mg (90.5% of theory). 0879 MS (ESI): 603 (MH), 0880 HPLC (analytic): 95.9% RT: 7.05 mm, column: Gromisil ODSB (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 42

2-2-Ethoxy-5-(1-methylimidazole-4-sulfonylamino)phenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0881

162

0882 Analogously to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 87.8 mg (0.486 mmol) of 1-methylimidazole-4-sulfonyl chloride and 0.10 ml (1.22 mmol) of pyridine in 6 ml of tetrahydrofurane overnight. Purification of the product over silica gel using ethyl acetate and methanol as mobile phase gives 65.2 mg (96.6% of theory). 0883 MS (ESI): 556 (MH), 0884 HPLC (analytic): 92.9% RT: 6.74 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 43

2-2-Ethoxy-5-methylsulfonylaminophenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo-5,1-1,2,4-triazin-4-one 0885

163

0886 Analogously to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 55.7 mg (0.486 mmol) of methanesulfonlyl chloride and 0.10 ml (1.22 mmol) of pyridine in 6 ml of tetrahydrofuran overnight. Purification of the product on silica gel using toluene and ethyl acetate from 8:2 to 5:5 gives 23.4 mg (39.3% of theory). 0887 MS (ESI): 490 (MH), 0888 TLC: Rf0.47 (toluene:ethyl acetate2.8).

EXAMPLE 44

2-2-Ethoxy-5-isopropylsulfonylaminophenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0889

164

0890 Analogusly to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 333 mg (2.34 mmol) of isopropylsulfonyl chloride and 0.12 ml (1.46 mmol) of pyridine in 6 ml tetrahydrofuran overnight. Purification of the product on 40 ml of silica gel using ethyl acetate and methanol as mobile phase gives 37.0 mg (49.0% of theory). 0891 MS (DCI/NH3): 518 (MH), 0892 TLC: Rf0.65 (toluene:ethyl acetate2:8).

EXAMPLE 45

2-2-Ethoxy-5-(4-morpholinylsulfonamido)phenyl-5-methyl-7-(2-ethylhleptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0893

165

0894 Analogously to the procedure of example 36, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 360 mg (1.94 mmol) of morpholine N-sulfonyl chloride and 0.10 ml (1.22 mmol) of pyridine in tetrahydrofuran overnight. Purification of the crude product on 40 ml of silica gel using toluene and ethyl acetate, 6:4 to 5:5, as mobile phase gives 9.3 mg (13.7% of theory). 0895 MS (ESI): 561 (MH), 0896 HPLC (analytic): 94.8% RT: 7.74 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 46

2-2-Ethoxy-5-(4-morpholinocarbonylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0897

166

0898 213 mg (0.601 mmol) of the amino compound from example 42A and 0.2 ml (1.43 mmol) of triethylamine are dissolved in 6 ml of tetrahydrofuran; the solution is cooled to 5 C., and 0.489 ml (4.22 mmol) of 4-morpholinocarbonyl chloride, dissolved in 4 ml of tetrahydrofuran, is injected. The reaction solution is stirred at room temperature overnight, ethyl acetate, NH4Cl solution and NaHCO3 solution are added, the organic phase is separated off, the aqueous phase is re-extracted 3 times with ethyl acetaie and the organic phases are combined, dried and concentrated. The product is chromatographed on 60 ml of silica gel using ethyl acetate/methanol as mobile phase. 0899 Yield: 275 mg (98% of theory). 0900 1H-NMR (200 MHz, DMSO): 1.30 (t, 3H), 1.58-2.07 (m, 8H), 2.48 (s, 3H), 3.12 (t, 4H), 3.41 (quin., 1H), 3.55 (t, 4H), 4.08 (quar., 2H), 7.08 (d, 1H), 7.55-7.62 (m, 2H), 8.56 (s, 1H).

EXAMPLE 47

2-5-(3,4-Dimethoxyphenylacetylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0901

167

0902 Analogously to the preparation of example 46, 100 mg (0.283 mmol) of the compound from example 42A are reacted with 182 mg (0.849 mmol) of 3,4-dimethoxyphenylacetyl chloride and 0.23 ml (2.84 mmol) of pyridine in 6 ml of tetrahydrofuran. 0903 Yield: 141 mg (93.9% of theory). 0904 1H-NMR (400 MHz, DMSO): 1.30 (t, 3H), 1.57-2.05 (m, 8H), 2.47 (s, 3H), 3.45 (quin., 1H), 3.53 (s, 2H), 3.73 (d, 6H), 4.07 (quar., 2H), 6.82-6.95 (m, 2H), 7.10 (d, 2H), 7.73 (m, 2H), 10.12 (s, 1H), 11.50 (s, 1H); 0905 MS (ESI): 532 (MH).

EXAMPLE 48

2-5-(1,4-Di-tert-butyloxycarbonyl-()-piperazine-2-carbonylamino)-2-ethoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0906

168

0907 110 mg (0.311 mmol) of the amino compound from example 42A and 247 mg (0.747 mmol) of N,N-di-tert-butyloxycarbonyl()-piperazine-2-carboxylic acid are sirred at room temperature in 30 ml of dichloromethane with 154 mg (0.747 mmol) of dicyclohexylcarbodiimide for 2 days. The reaction solution is poured onto 120 ml of silica gel and washed with dichloromethane, and the product is then eluted using cyclohexane and ethyl acetate in a gradient system of from 8:2 to 1:1. 0908 Yield: 203 mg (98.0% of theory). 0909 1H-NMR (200 MHz, DMSO): 1.12-1.44 (m, 21H), 1.57-2.07 (m, 8H), 2.45 (s, 3H), 2.76-3.04 (m, 1H), 3.38-3.94 (m, 5H), 4.08 (quar, 2H), 4.28-4.58 (m, 2H), 7.13 (d, 1H), 7.70 (m, 2H), 10.16 (s, 1H), 11.52 (s, 1H); 0910 MS (DCI/NH3): 666 (MH).

EXAMPLE 49

2-2-Ethoxy-5-(()-piperazine-2-carbonylamino)phenyl-5-methyl-7-cyclopentyl-3H -imidazo5,1-f1,2,4-triazin-4-one 0911

169

0912 132 mg (0.198 mmol) of the compound from example 48 are treated with 5 ml of trifluoroacetic acid for 90 minutes the solution is then concentrated dichloromethane and 10% strength NaHCO3 solution are added to the residue and the organic phase is dried and concentrated under reduced pressure. 0913 Yield: 59.4 mg (64.4% of theory). 0914 1H-NMR (200 MHz, CDCl3): 1.51 (t, 3H), 1.61-2.21 (m, 10H), 2.64 (s, 3H), 2.80-3.07 (m, 5H), 3.22 (dd, 1H), 3.48 (dd, 1H), 3.66 (quin., 1H), 4.20 (quar, 2H) 7.00 (d, 1H), 7.94 (dd, 1H), 8.07 (d, 1H) 9.12 (s, 1H).

EXAMPLE 50

2-2-Ethoxy-5-(4-methylpiperazineacetylamino)phenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0915

170

0916 Analogously to the preparation of example 48, 60 mg (0.17 mmol) of the amino compound from example 42A are reacted with 64.5 mg (0.407 mmol) of 4-methyl-1-piperazineacetic acid in the presence of 84.1 mg (0.407 mmmol) of dicyclohexylcarbodiimide in 20 ml of dichloromethane for 4 days. 0917 Yield:75.6 mg (90.2% of theory). 0918 MS (ESI): 494 (MH), 0919 HPLC (analytic): 66.0% RT: 2.13 min, column: Nucleosil C18 (1254 mm), mobile phase: 75% H2O with 1% trifluoroacetic acid 25% acetonitrile, flow rate:2 ml/min, 200-400 nm.

EXAMPLE 51

2-5-(4-Morpholinocarbonylamino)-2-propoxyphenyl-5-methyl-7-cyclopentyl-3H-imidazo5,1-f1,2,4-triazin-4-one 0920

171

0921 Unter argon, 0.32 g (4.082 mmol) of pyridine and, a little at a time, 0.449 g (3.0 mmol) of 4-morpholino-N-carbonyl chloride are added to 150 mg (0.408 mmol) of the amino compound from example 44A in 6 ml of tetrahydrofuran, and the mixture is stirred at room temperature overnight. The reaction solution is diluted with ethyl acetate and water, the aqueous phase is re-extracted with ethyl acetate and the combined organic phases are dried and concentrated under reduced pressure. The residue is chromatographed on 50 ml of silica gel using toluene and ethyl acetate in a gradient system. 0922 Yield: 139 mg (70.7% of theory). 0923 1H-NMR (300 MHz, DMSO): 0.93 (t, 3H), 1.57-2.08 (m, 10H), 2.48 (s, 3H), 3.42 (t, 4H), 3.50 (quin., 1H), 3.61 (t, 4H), 3.97 (t, 2H), 7.08 (d, 1H), 7.60 (m, 2H), 8.58 (s, 1H), 11.47 (s, 1H); 0924 MS (ESI): 481 (MH).

EXAMPLE 52

2-2-Ethoxy-5-(1,4-di-tert-butyloxycarbonyl-()-piperazine-2-carbonylamino)-phenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0925

172

0926 Analogously to the procedure of example 48, 186 mg (0.452 mmol) of the amino compound from example 50A are reacted with 358 mg (1.085 mmol) of N,N-di-tert-butyloxycarbonyl-()-piperazine-2-carboxtlic acid in the presence of 224 mg (1.085 mmol) of dicyclohexylcarbodiimide in 20 ml of dichloromethane for 2 days. The crude product is purified by chromatography on 150 ml of silica gel eluted with cyclohexane and ethyl acetate in gradient system of from 8:2 to 1:1. 0927 Yield: 295 mg (90.2% of theory). 0928 MS (DCI/NH3): 724 (MH), 0929 HPLC (analytic): 98.0% RT: 6.68 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 53

2-2-Ethoxy-5-(1,4-di-tert-butyloxycarbonyl-()-piperazine-2-carbonylamino)-phenyl-5-methyl-7-(2-ethylheptyl)-3H-imidazo5,1-f1,2,4-triazin-4-one 0930

173

0931 Analogously to the procedure of example 49, 358 mg (0.495 mmol) of the compound from example 52 are treated with 15 ml of trifluoroacetic acid. 0932 Yield: 260 mg (100% of theory). 0933 1H-NMR (200 MHz, CDCl3): 0.82 (quar, 6H), 1.06-1.35 (m, 9H), 1.53 (t, 3H), 1.62-1.98 (m, 7H), 2.64 (s, 3H), 2.80-3.41 (mm, 6H), 3.48 (quin., 1H), 4.21 (quar., 2H), 7.00 (d, 1H), 7.95 (dd, 1H), 8.01 (dd, 1H), 9.00 (s, 1H); 0934 MS (DCI/NH3): 524 (MH), 0935 HPLC (analytic): 97.6% RT: 4.57 min, column: Gromsil ODSB (2504.6 mm), mobile phase: water/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 54

1-3-(7-Cyclopentyl-5-methyl-4-oxo-3,4-dihydroimidazo5,1-f1,2,4-triazin-2-yl)-4-propoxyphenyl-3-(4-trifluoromethylthiophenyl)-urea 0936

174

0937 Unter argon, 179 mg (0.816 mmol) of 4-(trifluoromethylthio)phenyl isocyanate, dissolved in 4 ml of tetrahydrofuran, are added to a solution of 150 mg (0.408 mmol) of the amino compound from example 44A in 8 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 1 hour. Ethyl acetate, water and 6 ml of NH4Cl solution are added to the reaction solution, the organic phase is separated off, the aqueous layer is re-extracted with ethyl acetate and the combined organic phases are dried and concentrated under reduced pressure. The residue is chromatographed on 40 ml of silica gel using toluene and ethyl acetate in a gradient system of from 9:1 to 6:4. 0938 Yield: 77.7 mg (32.4% of theory). 0939 1H-NMR (200 MHz, DMSO): 0.95 (t, 3H), 1.52-2.10 (m, 10H), 2.47 (s, 3H), 3.50 (quin., 1H), 3.98 (t, 2H), 7.12 (d, 1H), 7.60 (s, 6H), 8.82 (s, 1H), 9.08 (s, 1H), 11.47 (s, 1H); 0940 MS (DCI/NH3): 587 (MH). 0941 Additionally, a 2nd fraction contaminated with a little starting material is obtained (185 mg77.3% of theory).

EXAMPLE 55

1-3-(7-(1-Ethylpropyl)-5-methyl-4-oxo-3,4-dihydroimidazo5,1-f1,2,4-triazin-2-yl )-4-ethoxyphenyl-3-(4-trifluoromethylthiophenyl)-urea 0942

175

0943 Analogously to the procedure of example 54, 230 mg (0.647 mmol) of the amino compound from example 48A are reacted with 284 mg (1.29 mmol) of 4-(trifluoromethylthio)phenyl isocyanate in 20 ml of tetrahydrofuran for 4 hours. The crude product is purified by silica gel chromatography using toluene and ethyl acetate as mobile phase. 0944 Yield: 138 mg (37.2% of theory). 0945 1H-NMR (200 MHz, DMSO): 0.77 (t, 6H), 1.30 (t, 3H), 1.63-1.81 (m, 4H), 2.50 (s, 3H), 3.11 (quin., 1H), 4.09 (quar, 2H), 7.12 (d, 1H), 7.56 (d, 1H), 7.62 (s, 4H), 7.68 (d, 1H), 8.34 (s, 1H), 13.52 (s, 1H); 0946 MS (ESI): 575 (MH).

EXAMPLE 56

1-3-(7-(1-Ethylpropyl)-5-methyl-4-oxo-3,4-dihydroimidazo5,1-f1,2,4-triazin-2-yl)-4-ethoxy-phenyl-3-(4-fluorophenylsulfonyl)-urea 0947

176

0948 The preparation was carried out analogously to the procedure of example 54 using 230 mg (0.647 mmol) of the amino compound from example 48A and 260 mg (1.294 mmol) of 4-fluorobenzenesulfonyl isocyanate in 15 ml of tetrahydrofuran. The mixture is stirred at room temperature for 4 hours, and the crude product is then isolated on silica gel using toluene and ethyl acetate. 0949 Yield: 54.6 mg (15.2% of theory). 0950 MS (ESI): 557 (MH), 0951 HPLC (analytic): 70.0% RT: 6.68 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 57

1-3-(7-Cyclopentyl-5-methyl-4-oxo-3,4-dihydroimidazo5,1-f1,2,4-triazin-2-yl)-4-propoxyphenyl-3-(4-fluorophenylsulfonyl)-urea 0952

177

0953 The preparation is carried out analogously to the procedure of example 54 using 150 mg (0.408 mmol) of the amino compound from example 44A and 411 mg (2.04 mmol) of 4-fluorobenzenesulfonyl isocyanate in 12 ml of tetrahydrofuran, which are reacted overnight. 0954 Yield: 163 mg (70.1% of theory). 0955 1H-NMR (400 MHz, DMSO): 0.90 (t, 3H), 1.54-2.08 (m, 10H), 2.45 (s, 3H), 3.45 (quin., 1H), 3.88 (t, 2H), 6.92 (d, 1H), 7.17 (t, 2H), 7.53 (d, 1H), 7.63 (s, 1H), 7.82 (m, 2H), 8.47 (s, 1H), 11.37 (s, 1H); 0956 MS (ESI): 569 (MH).

EXAMPLE 58

1-3-7-(2-Ethylheptyl)-5-methyl-4-oxo-3,4-dihydroimidazo5,1-f1,2,4-triazin-2-yl-4-ethoxyphenl-3-(4-fluorophenylsulfonyl)-urea 0957

178

0958 Analogously to the procedure of example 54, 50 mg (0.121 mmol) of the amino compound from example 50A are reacted with 548 mg (2.72 mmol) of 4-fluorobenzenesulfonyl isocyanate in tetrahydrofuran for 2 days. Purification of the crude product on silica gel using toluene and ethyl acetate, 4:6 to 3:7, as mobile phase, gives 36.2 mg (48.6% of theory). 0959 MS (ESI): 613 (MH), 0960 HPLC (analytic): 81.0% RT: 4.92 min, column: Nucleosil C18 (1254 mm), mobile phase: 0.01 m H3PO4/acetonitrile (gradient), flow rate:2 ml/min, 200-400 nm.

EXAMPLE 59 0961

179

0962 12.4 l (0.16 mmol) of chloroacetyl chloride were slowly added dropwise to a solution of 50 mg (0.14 mmol) of the amine example 42A in 1,2-dichloroethane and 21.6 l (0.16 mmol) of Et3N. After 2 h, 1 ml of sat. NaHCO3 solution was added and the mixture was filtered through 1 g of Extrelut (CH2Cl2). The crude product was re-dissolved in 1,2-dichloroethane, 87.1 l (0.34 mmol) of morpholine were added and the mixture was heated at 100 C. for 10 h. The mixture was stirred at room temperature overnight, 0.5 ml of sat. NaHCO3 solution was added and the mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (ethyl acetate). The concentrated crude product was purified by preparative thin-layer chromatography (CH2Cl2:MeOH15:1). This gave 18.9 mg (34.5%) of the desired product (81% pure according to HPLC). 0963 MS (ESI): m/z (%) 481 MH (100) 0964 1H-NMR (200 MHz, D6-DMSO): 1.29 (t, 3H, CH3), 1.55-2.05 (m, 8H, CH2), 3.12 (s, 2H, CH2), 3.45 (m, 1H, CH), 3.63 (t, 4H, CH2), 4.07 (g, 2H, CH2), 7.11 (d, 1H), 7.76 (m, 2H), 9.78 (bs, 1H, NH), 11.53 (bs, 1H, NH).

EXAMPLE 60 0965

180

0966 12.3 l (0.014 mmol) of chlorosulfonyl isocyanate were slowly added dropwise to a solution, cooled to 0 C. of 50 mg (0.014 mmol) of the amine example 42A in 1,2-dichloroethane. The mixture was allowed to warm to room temperature and then stirred for another hour, and 12.3 mg (0.014 mmol) of morpholine and 1 equivalent of morpholinomethyl-polystyrene (3.47 mmol/g) were added. The mixture was stirred overnight and then filtered through 1 g of silica gel (ethyl acetate), and the crude product was purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 2.3 mg (3.0%) of the sulfonylurea derivative (91% pure according to HPLC) 0967 1H-NMR (200 MHz, CDCl3): 1.55 (t, 3H, CH3), 1.64-2.15 (m, 8H), 2.63 (s, 3H, CH3), 3.51 (t, 4H, CH2), 3.64 (m, 1H), 3.78 (t, 4H, CH2), 4.23 (g, 2H, CH2), 6.38 (bs, 1H, NH), 7.02 (d, 1H), 7.73 (dd, 1H), 7.86 (d, 1H), 9.95 (bs, 1H, NH).

EXAMPLE 61 0968

181

0969 Initially 7.4 l (0.08 mmol) of chlorosulfonyl isocyanate were added dropwise to a solution, cooled to 0 C, of 30 mg (0.08 mmol) of the amine example 48A in 1,2-dichloroethlane. The mixture was allowed to wain to room temperature and then stirred for another hour, and 7.3 mg (0.08 mmol) of morpholine and a suspension of 30 mg of morpholinomethyl-polystyrene (3.47 mmol/g) in 1,2-dichloroethane were added. After 3 h, the reaction mixture was filtered and the crude product was purified chromatographically (gradient: CH2Cl2CH2Cl2:MeOH10040:1). This gave 4.8 mg (10.9%) of the sulfonylurea (91% pure according to HPLC). 0970 1H-NMR (200 MHz, D6-DMSO): 0.75 (t, 6H, CH3), 1.29 (t, 3H, CH3), 1.72 (m, 4H, CH2), 2.53 (s, CH3 shoulder o/D6-DMSO), 3.12 (m, 1H, CH), 3.42 (bt, 4H, CH2), 3.59 (bt, 4H, CH2), 4.06 (g, 2H, CH2), 7.07 (d, 1H), 7.57 (m, 2H), 8.55 (bs, 1H, NH), 11.45 (bs, 1H, NH).

EXAMPLE 62 0971

182

0972 Analogously to example 61, 30 mg (0.08 mmol) of the amine example 48A were converted into 9.5 mg (20.1%) of the sulfonylurea (86% pure according to HPLC). 0973 MS (ESI): m/z (%)561 MH (30) 0974 1H-NMR (300 MHz, D3COD): 0.80 (t, 6H, CH3), 1.42 (t, 3H, CH3), 1.83 (m, 4H, CH2, CH), 2.34 (s, 3H CH3), 2.52 (t, 4H, CH2), 2.54 (s, 3H, CH3), 3.57 (t, 4H, CH2), 4.17 (g, 2H, CH2), 7.09 (d, 1H), 7.49 (dd, 1H), 7.69 (d, 1H).

EXAMPLE 63 0975

183

0976 A second solution of 15 mg (0.04 mmol) of the amine example 50A in 1 ml of dioxane was slowly added dropwise to a solution cooled to 78 C., of 3.2 mg (0.02 mmol) of chlorosulfonyl isocyanate in 1 ml of ether. A suspension was formed, which was briefly warmed to 0 C, and then stirred at 78 C. for 1 h, and 12.6 mg (0.14 mmol) of morpholine were then added at 0 C. After 2 h, 2 ml of 1 M H2SO4 wvere added, and the mixture was filtered through 3 g of Extrelut (mobile phase: CH2Cl2). The concentrated crude product was purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1) giving 6.6 mg (30.2%) of the desired product. 0977 MS (ESI): m/z (%)603 MH (100) 0978 1H-NMR (300 MHz, D3COD): 0.86 (m, 6H, 2CH3), 1.24 (m, 8H, 4CH2), 1.47 (t, 3H, CH3), 1.71-2.02 (m, 4H, 2CH2), 2.63 (s, 3H, CH3), 3.63-3.85 (m, 7H, 3CH2, CH), 4.23 (g, 2H, CH2O), 7.18 (d, 1H), 7.76 (dd, 1H), 8.06 (d, 1H).

EXAMPLE 64 0979

184

0980 Analogously to example 63, 14.9 mg (0.04 mmol) of the amine example 50A were reacted with 3.2 mg (0.02 mmol) of chlorosulfonyl isocyanate and 14.5 mg (0.14 mmol) of N-methylpiperazne. Preparative thin-layer chromatography gave 2.4 mg (10.8%) of the desired product. 0981 MS (ESI): m/z (%)616 MH (100) 0982 1H-NMR (200 MHz, CDCl3): 0.83 (m, 6H, 2CH3), 1.09-1.34 (m, 11H, 4CH2 CH3), 1.85 (m, 4H, 2CH2), 2.31 (s, 3H, CH3), 2.49 (bt, 4H, 2CH2), 2.65 (s, 3H, CH3), 3.40 (bt, 4H, 2CH2), 4.01 (s, 2H, CH2), 4.26 (g, 2H, CH2), 7.05 (d, 1H), 7.83 (dd, 1H), 8.13 (d, 1H), 8.29 (bs, 1H).

EXAMPLE 65 0983

185

0984 A solution of 50 mg (0.14 mmol) of the amine example 42A, 18.0 mg (0.17 mmol) of freshly distilled benzaldehyde and 23.5 mg (0.17 mmol) of diethyl phosphite was heated at 80 C. for 20 h. The volatile components were removed under high vacuum and the residue was purified chromatographically (gradient: CH2Cl2CH2Cl2:MeOH10:1). The two product-containing fractions were combined and re-purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 20.1 mg (24.5%) of the desired product. 0985 MS (ESI): m/z (%)580 MH (100) 0986 1H-NMR (200 MHz, D6-DMSO): 1.05 (t, 3H, CH3), 1.22 (m, 9H, 3CH2), 1.55-2.05 (m, 8H, 4CH2), 3.65-4.15 (m, 7H, 3CH2, CH), 5.02 (dd, 1H, CHN), 6.32 (dd, 1H, NH), 6.90 (m, 2H), 7.05 (d, 1H), 7.29 (m, 3H), 7.52 (m, 2H), 11.32 (bs, 1H, NH).

EXAMPLE 66 0987

186

0988 19 l (0.16 mmol) of diphosgene were added dropwise to a solution of 80 mg (0.23 mmol) of the amine example 48A in 1,4-dioxane, and the mixture was stirred for 20 h. Following concentration under reduced pressure, the residue was twice taken up in benzenze and re-concentrated. 30 mg (0.07 mmol) of the resulting carbamoyl chloride were, as a crude product, dissolved in 1 ml of 1,2-dichloroethane, 8.6 mg (0.09 mmol) of N-methylpiperazine were added and the mixture was stirred at room temperature for 20 h. Quenching with 0.5 ml of H2O and filtration through Extrelut/silica gel (CH2Cl2:MeOHl95:5) gave 30 mg (87%) of the urea derivative (90% pure according to HPLC). 0989 MS (DCIm NH3): m/z (%) 482 MH (10) 0990 1H-NMR (200 MHz, D6-DMSO): 0.75 (t, 6H, CH3), 1.28 (t, 3H, CH3), 1.72 (m, 4H, CH2), 2.22 (bt, 4H, CH2), 3.12 (m, 1H, CH), 3.43 (bt, 4H, CH2), 3.91 (s, 3H, CH3), 4.05 (g, 2H, CH2), 7.05 (d, 1H), 7.58 (m, 2H), 8.53 (bs, 1H, NH), 11.48 (bs, 1H, NH).

EXAMPLE 67 0991

187

0992 Analogously to example 66, 30 mg (0.08 mmol) of the carbamoyl chloride were reacted with 7.51 (0.09 mmol) of morpholine. For work-up, 0.5 ml of 2 N HCl were added, and the mixture wvas filtered through 500 mg of Extrelut and 500 mg of SiO2 (CH2Cl2). This gave 26.2 mg (77.9%) of the urea (95.2% pure according to HPLC). 0993 MS (DCI, NH3): m/z (%) 469 MH (10%); 382 M87 (100) 0994 1H-NMR (200 MHz, D6-DMSO): 0.75 (t, 6H, CH3), 1.28 (t, 3H, CH3), 1.72 (m, 4H, CH2), 3.10 (m, 1H, CH), 3.42 (t, 4H, CH2), 3.59 (t, 4H, CH2), 4.06 (g, 2H, CH2), 7.05 (d, 1H) 7.58 (m, 2H), 8.57 (bs, 1H, NH) 11.49 (bs, 1H, NH)

EXAMPLE 68 0995

188

0996 Analogously to example 66, 30 mg (0.08 mmol) of the carbamoyl chloride were reacted to give 33 mg (95%) of the urea (87% pure according to HPLC). 0997 MS (DCI, NH3): m/z (%) 485 MH (10); 382 M87 (100) 0998 1H-NMR (200 MHz, D6-DMSO): 0.74 (t, 6H, CH3), 0.83 (t, 3H, CH3), 1.28 (t, 3H, CH3), 1.50 (m, 2H, CH2), 1.72 (m, 4H, CH2), 3.05-3.61 (m, 6H, CH2), 4.07 (g, 2H, CH2), 7.07 (d, 1H), 7.51 (m, 2H), 8.42 (bs, 1H, NH), 11.49 (bs, 1H, NH). 0999 In parallel synthesis analogously to example 66, the compounds of Table 1 below were prepared from the amine example 48A, diphosgene and the appropriate amine. Neutral end products were quenched with 0.5 ml of 1 molar sulfuric acid solution, basic end products were quenched with 0.5 ml of saturated sodium bicarbonate solution. 1HPLCMWarea %Ex. No.Structureg/molat 210 nmMz H69

189

518.62180519 70

190

510.64287511 71

191

524.66976525 72

192

497.64669498 73

193

524.66982525 74

194

552.72382553 75

195

524.66972525

EXAMPLE 76 1000

196

1001 A solution of 300 mg (0.83 mmol) of the chloromethyl compound example 51 A and 217 mg (2.5 mmol) of morphloline in 10 ml of 1,2-dichloroethane was heated at 80 C. for 15 h. The resulting precipitate was filtered off with suction. The concentrated crude product was triturated with ether and filtered, giving a mixture of product and starting material which was purified chromatographically (gradient CH2Cl2/MeOH50:120:1). This gave 163 mg (47.8%) of the desired product. 1002 MS (ESI): m/z412 MH (100) 1003 1H-NMR (200 MHz, CDCl3): 1.05 (t, 3H, CH3); 1.57 (t, 3H, CH3); 1.89 (m, 2H, CH2); 2.48 (bt, 4H, 2CH2); 2.65 (s, 3H, CH3); 3.02 (t, 2H, CH2); 3.52 (s, 2H, CH2); 3.72 (t, 4H. 2CH2); 4.25 (g, 2H, CH2); 7.02 (d, 1H); 7.49 (dd, 1H); 8.08 (d, 1H); 9.90 (bs, 1H, NH).

EXAMPLE 77 1004

197

1005 A solution of 300 mg (0.8 mmol) of the chloromethyl compound example 51A and 222 mg (2.5 mmol) of N-ethyl-2-aminoethanol in 10 ml of 1,2-dichloromethane was heated at reflux for 6 hours, cooled and, after filtration, concentrated under reduced pressure. Chromatographic purification (gradient: CH2Cl2CH2Cl2/MeOH10:1) gave 190 mg (55%) of slightly contaminated product and 68 mg (20%) of purer product. 1006 MS (ESI): m/z414 MH (100) 1007 1H-NMR (200 MHz, CDCl3): 1.05 (t, 3H, CH3); 1.09 (t, 3H, CH3), 1.57 (t, 3H, CH3); 1.88 (m, 2H, CH2); 2.63 (m, 4H, 2CH2); 2.65 (s, 3H, CH3); 3.01 (t, 2H, CH2); 3.59 (t, 2H, CH2); 3.65 (s, 2H, CH2); 4.25 (m, 2H, CH2); 7.02 (d, 1H); 7.43 (dd, 1H); 8.08 (d, 1H); 9.95 (bs, 1H, NH).

EXAMPLE 78 1008

198

1009 6.7 mg (0.07 mmol) of N-methylpiperazine and 8.4 mg (0.08 mmol) of Et3N were added to a solution of 20 mg (0.06 mmol) of the chloromethyl compound example 51A in 0.5 ml of 1,2-dichloroethane, and the mixture was stirred at room temperature for 15 h. 0.5 ml of sat. NaHCO3 solution was added, and the mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (mobile phase: ethyl acetate). The mixture was concentrated and purified by thin-layer chromatography (CH2Cl2:MeOH10:1). This gave 7.7 mg (32.7%) of the desired product. 1010 MS (ESI): m/z (%)425 MH (50) 1011 1H-NMR (200 MHz, CD3OD): 1.02 (t, 3H, CH3), 1.45 (t, 3H, CH3), 1.84 (m, 2H, CH2), 2.33 (s, 3H, CH3), 2.43-2.65 (m, 8H, 4CH2), 2.58 (s, 3H, CH3), 2.97 (t, 2H, CH2), 3.56 (s, 2H, CH2), 4.20 (g, 2H, CH2), 7.16 (d, 1H), 7.51 (dd, 1H), 7.72 (d, 1H).

EXAMPLE 79 1012

199

1013 Analogously to example 78, 20 mg (0.06 mmol) of the chloromethyl compound example 51A were reacted with 6.9 mg (0.07 mmol) of N-propyl-2-aminoethanol and 8.4 mg (0.08 mmol) of Et3N. Preparive thin-layer chhromatography (CH2Cl2:MeOH10:1) gave 3.6 mg (15.2%) of the desired product. 1014 1H-NMR (200 MHz, CD3OD): 0.89 (t, 3H, CH3), 0.99 (t, 3H, CH3), 1.44 (t, 3H, CH3), 1.55 (m, 2H, CH2), 1.82 (g, 2H, CH2), 2.48 (t, 2H, CH2), 2.58 (s, 3H, CH3), 2.64 (t, 2H, CH2), 2.96 (t, 2H, CH2), 3.62 (t, 2H, CH2), 3.67 (s, 2H, CH2), 4.18 (g, 2H, CH2), 4.60 (bs, 1H, OH), 7.12 (d, 1H), 7.50 (dd, 1H), 7.73 (d, 1H).

EXAMPLE 80 1015

200

1016 Analogously to example 76, 300 mg (0.83 mmol) of the chloromethyl compound example 51A were reacted with 424 mg (2.5 mmol) of 4-(-dioxazinyl)piperidine at 80 C. After 15 h, H2O was added. Repeated chromatographic work-up gave 14.5 mg (3.5%) of the desired product. 1017 MS (ESI): m/z (%)495 MH (100) 1018 1H-NMR (200 MHz, CDCl3): 1.05 (1.3H, CH3), 1.56 (t, 3H, CH3), 1.70-2.10 (m, 8H, 4CH2), 1.90 (m, 2H, CH2), 2.64 (s, 3H, CH3), 3.02 (t, 2H, CH2), 3.51 (s, 2H, CH2), 4.03 (t, 2H, CH2), 4.25 (g, 2H, CH2), 4.30 (m, 2H, CH2), 7.01 (d, 1H), 7.47 (dd, 1H), 8.05 (d, 1H), 10.91 (bs, 1H, NH). 1019 In a parallel synthesis analogously to example 78, the compounds of the table below were prepared from the chloromethyl compound example 51 A and the appropriate amine. If after 24 h at RT, there was still starting material detected in the TLC, stirring was continued at 60 C. for another 24 h. 2HPLCMWarea %Ex. No.Structureg/molat 210 nmMz H81

201

461.56951462 82

202

489.62362490 83

203

457.57845458 84

204

453.61366454 85

205

500.64956501 86

206

516.64953517 87

207

487.6164488 88

208

488.59771489 89

209

482.58872483

1020 In a parallel synthesis analogously to example 78, the compounds of the table below were prepared from the chloromethyl compound example 53 A and the appropriate amine. If, after 24 h at RT, there was still starting material detectable in the TLC, stirring was continued at 60 C. for another 24 h. 3HPLCMWarea %Ex. No.Structureg/molat 210 nmMz H90

210

466.63176100467.3 91

211

453.589492.65454.3 92

212

467.6164986.42468.3 93

213

529.69103100530.3 94

214

494.6423173.53495.3

EXAMPLE 95 1021

215

1022 Analogously to example 76, 50 mg (0.12 mmol) of the chloromethyl compound example 55A were reacted with 311.5 mg (0.36 mmol) of morpholine at 80 C. for 5 h. Purification by thin-layer chromatography (CH2Cl2/MeOH10:1) gave 25.5 mg (46%) of the desired product. 1023 MS (ESI): m/z (%)466 MH (100) 1024 1H-NMR (200 MHz, CDCl3): 1.56 (t, 3H, CH3); 1.57-2.12 (m, 12H, 6CH2); 2.48 (bt, 4H, 2CH2); 2.62 (s, 3H, CH3); 3.43 (m, 1H, CH); 3.52 (s, 2H, CH2); 3.72 (bt, 4H, 2CH2); 4.25 (g, 2H, CH2); 7.01 (d, 1H); 7.47 (dd, 1H); 8.11 (d, 1H); 9.89 (bs, 1H, NH).

EXAMPLE 96 1025

216

1026 Analogously to example 76, 50 mg (0.12 mmol) of the chloromethyl compound example 55A were reacted with 41.3 mg (0.36 mmol) of N-ethylpiperazine at 80 C. for 15 h. Purification by, thin-layer chromatography (CH2Cl2:MeOH5:1) gave 18.9 mg (32%) of the desired product (92% pure acording to HPLC). 1027 MS (ESI): m/z (%)493 MH (56) 1028 1H-NMR (200 MHz, CDCl3): 1.09 (t, 3H, CH3); 1.56 (t, 3H, CH3); 1.57-2.12 (m, 12H, 6CH2); 2.44 (g, 2H, CH2); 2.52 (bm, 8H, 4CH2); 2.66 (s, 3H, CH3); 3.42 (m, 1H, CH); 3.54 (s, 2H, CH2); 4.25 (g, 2H, CH2); 6.99 (d, 1H); 7.43 (dd, 1H); 8.10 (d, 1H); 9.89 (bs, 1H, NH).

EXAMPLE 97 1029

217

1030 Analogously to example 76, 50 mg (0.12 mmol) of the chloromethyl compound example 55A were reacted with 32 mg (0.36 mmol) of N-ethyl-2-aminoethanol at 80 C. for 15 h. Purification by preparative thin-larer chromatography (CH2Cl2:MeOH20:1) gave 17.3 mg (31%) of the desired product (87% pure according to HPLC). 1031 MS (ESI): m/z (%)468 MH (80) 1032 1H-NMR (200 MHz, D6-DMSO): 0.99 (t, 3H, CH3); 1.28 (t, 3H, CH3); 1.42-2.05 (m, 12H); 3.46 (g, 2H, CH2); 3.55 (s, 2H, CH2); 4.07 (g,2H, CH2); 4.35 (m, 1H, CH); 7.09 (d, 1H); 7.43 (dd, 1H); 7.49 (d, 1H).

EXAMPLE 98 1033

218

1034 Analogously to example 76, 50 mg (0.12 mmol) of the chloromethyl compound example 55A were reacted with 61 mg (0.36 mmol) of 4-(1-dioxazinyl)piperidine. This gave 17 mg (26%) of the desired product. 1035 MS (ESI): m/z (%)549 MH (50) 1036 1H-NMR (200 MHz, CDCl3): 1.5-2.1 (m, 25H); 2.63 (s, 3H, CH3); 2.93 (bd, 1H); 3.45 (m, 1H, CH); 3.52 (s, 2H, CH2); 4.02 (m, 2H, CH2); 4.2-4.4 (m, 4H, 2CH2); 6.95 (d, 1H); 7.45 (dd, 1H); 8.08 (d, 1H); 9.85 (bs, 1H, NH).

EXAMPLE 99 1037

219

1038 Analogously to example 76, 60 mg (0.14 mmol) of the chloromethyl compound example 56A were heated with 36.6 mg (0.42 mmol) of morpholine at 80 C. for 15 h. Preparative thin-layer chromatography (CH2Cl2:MeOH10:1) gave 38.7 mg (57.7%) of the desired product. 1039 MS (ESI): m/z (%)480 MH (100) 1040 1H-NMR (200 MHz, CDCl3): 133 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.60-2.10 (m, 12H, 6CH2), 2.49 (m, 4H, 2CH2), 3.02 (g, 2H, CH2), 3.45 (m, 1H, CH), 3.54 (s, 2H, CH2), 3.73 (bt, 4H, 2CH2), 4.25 (g, 2H, CH2), 7.02 (d, 1H), 7.46 (dd, 1H), 8.11 (d, 1H), 9.90 (bs, 1H, NH).

EXAMPLE 100 1041

220

1042 20.8 l (0.15 mmol) of Et3N were added to a suspension of 50 mg (0.13 mmol) of the chloromethyl compound example 54A in 1 ml of triethyl phosphite, and the mixture was initially heated at 100 C. for 30 min and then stirned at room temperature for another 48 h. 0.5 ml of sat. NaHCO3 solution was added, and the mixture was filtered through a two-phase cartridge (500 mg of Extrelut/500 mg of SiO2, mobile phase: ethyl acetate). The mixture was concentrated under reduced pressure and purified by thin-layer chromatography (CH2Cl2:MeOH20:1). This eave 14.4 mg (23%) of the desired product. 1043 MS (ESI): m/z (%)503MH (100) 1044 1H-NMR (200 MHz, CDCl3): 1.30 (t, 6H, 2CH3), 1.58 (t, 3H, CH3), 1.61-2.17 (m, 8H, 4CH2), 3.02 (g, 2H, CH2), 3.19 (d, 2H, CH2P), 3.62 (m, 1H, CH), 4.07 (g, 4H, 2CH2), 4.24 (g, 2H, CH2), 7.02 (g, 1H), 7.45 (dt, 1H), 8.02 (t, 1H), 9.89 (bs, 1H, NH).

EXAMPLE 101 1045

221

1046 Analogously to example 100, 50 mg (0.14 mmol) of the chloromethyl compound example 51A were reacted with 1 ml of triethyl phosphite and 23.1 l (0.17 mmol) of Et3N. Preparative thin-layer chromatographIy (CH2Cl2:MeOH20.1) gave 20 mg of the desired product, which was contaminated with the unsubstituted triazinone NUN 4792 (2:1 acccording to HPLC). 1047 MS (ESI): m/z (%)463 MH (100) 1048 1H-NMR (200 MHz, CDCl3): 1.03 (t, 3H, CH3), 1.29 (t, 6H, 2CH2), 1.58 (t, 3H, CH3), 1.89 (m, 2H, CH2), 2.65 (s, 3H, CH), 3.02 (g, 2H, CH2), 3.19 (d, 2H, CH2P), 4.08 (m, 4H, 2CH2), 4.25 (g, 2H, CH2), 7.03 (d, 1H), 7.48 (dt, 1H), 8.05 (t, 1H), 9.95 (bs, 1H, NH).

EXAMPLE 102 1049

222

1050 0.2 g (3.0 mmol) of NaN3 was added to a suspension of 1 g (2.7 mmol) of the chloroethyl compound example 51A in 30 ml of DMF, and the mixture was stined for 17 h. 1 M NaOH was added, and the mixture was extracted twice with ethyl acetate. The oroanic phase was dried over MgSO4 and concentrated under high vacuum (the sample was wwarmed only in a lukewarm water bath), giving 0.82 g (80.5%) of the desired product. 1051 MS (DCI, NH3): m/z (%)368 MH (100) 1052 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.32 (t, 3H, CH3), 1.73 (m, 2H, CH2), 2.83 (t, 2H, CH2), 4.12 (g, 2H, CH2), 4.45 (s, 2H, CH2), 7.20 (d, 1H), 7.54 (m, 1H), 11.57 (bs, 1H, NH).

EXAMPLE 103 1053

223

1054 48 mg (0.73 mmol) of NaN3 were added to a suspension of 250 mg (0.66 mmol) of the chloromethyl compound example 52A in 6 ml of DMF, and the mixture was stirred at room temperature for 17 h. 1 N NaOH was added, and the mixture was then extracted twice with ethyl acetate and the extracts were concentrated under reduced pressure and purified chromatographically (gradient:cyclohexane:ethyl acetate5:11:2). This gave 68 mng (28%) of the azide (88% according to HPLC). 1055 MS (ESI): m/z (%)382 MH (100) 1056 1H-NMR (400 MHz, CDCl3): 1.03 (t, 3H, CH3); 1.33 (t, 3H, CH3); 1.58 (t, 3H, CH3), 1.89 (m, 2H, CH2); 3.01-3.07 (m, 4H, 2CH2) 4.26 (g, 2H, CH2); 4.49 (s, 2H, CH2); 7.07 (d, 1H); 7.46 (dd, 1H); 8.09 (d, 1H); 9.86 (bs, 1H, NH).

EXAMPLE 104 1057

224

1058 36 mg (0.55 mmol) of NaN3 were added to a suspension of 200 mg (0.5 mmol) of the chloromethyl compound example 54A in 6 ml of DMF, and after 17 h at room temperature, 1 M NaOH was added. The aqueous phase was extracted twice with ethyl acetate and the organic phase was dried over MgSO4 and concentrated under reduced pressure. Chromatographic purification (cyclohexane:ethyl acetate1:1) gave 105 mng (52%) of the azide (75% according to HPLC). 1059 MS (ESI): m/z (%)408 MH (100) 1060 1H-NMR (200 MHz, CDCl3): 1.32 (t, 3H, CH3); 1.57 (t, 3H, CH3); 1.68-2.25 (m, 8H, CH2); 3.02 (g, 2H, CH2); 3.63 (m, 1H, CH); 4.27 (g, 2H, CH2); 4.39 (s, 2H, CH2); 7.06 (d, 1H); 7.45 (dd, 1H): 8.11 (d, 1H); 9.84 (bs, 1H, NH).

EXAMPLE 105 1061

225

1062 Analogously to example 102, 150 mg of the chloromethyl compound example 55a were reacted. Chromatographic purification (gradient: CH2Cl2CH2Cl2:MeOH110:1) gave 35.4 mg (23%) of the azide (67% pure according to HPLC). 1063 MS (ESI): m/z (%)422 MH (100) 1064 1H-NMR (400 MHz, CDCl3): 1.56 (t, 3H, CH3); 1.59-2.09 (m, 12H, 6CH2); 2.64 (s, 3H, CH3), 3.45 (m, 1H, CH); 4.24 (g, 2H, CH2); 4.38 (s, 2H, CH2); 7.08 (d, 1H); 7.45 (dd, 1H); 8.09 (d, 1H); 9.82 (bs, 1H, NH).

EXAMPLE 106 1065

226

1066 DMF was added dropwise to a suspension of 40 mg (0.11 mmol) of the azide example 102 in 1 ml DME until a homogeneous solution was formed, and 13.3 mg (0.16 mmol) of methyl propiolate were then added dropwise. The mixture was heated under reflux for 20 h, the solvent was condensed off under high vacuum and 1 ml of H2O was added to the residue. Following filtration through 1 g of Extrelut (mobile phase: ethyl acetate), the concentrated crude product was purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 24.3 mg (49.4%) of the desired product as a mixture of regioisomers (12.5:1 according to NMR) 1067 MS (ESI): m/z (%)452 MH (100) 1068 Main regioisomer: 1069 1H-NMR (200 MHz, CDCl3): 1.03 (t, 3H, CH3), 1.57 (t, 3H, CH3), 1.98 (m, 2H, CH2), 2.64 (s, 3H, CH3), 2.99 (t, 2H, CH2), 3.95 (s, 3H, OCH3), 4.27 (g, 2H, CH2), 5.62 (s, 2H, CH2), 7.08 (d, 1H), 7.43 (dd, 1H), 8.05 (s, 1H), 8.11 (d, 1H), 9.79 (bs, 1H, NH). 1070 The compounds of the table below were prepared in a parallel synthesis analogously to example 106 from the azide example 102. In each case, a 3-fold excess of alkyne was used. 4HPLCMWarea %Ex. No.Structureg/molat 210 nmMz H107

227

451.5388.4452.5327 108

228

437.51100438.5056 109

229

465.52100466.5161 110

230

507.6482.7508.641 111

231

481.56100482.5592 112

232

451.53100452.5327 113

233

537.58100538.5803 114

234

507.6493.5508.6439 115

235

465.56100466.5598 116

236

493.6196.5494.614 117

237

499.58100500.5773 118

238

554.7097.4555.7009 119

239

481.56100482.5592 120

240

507.60100508.5974 121

241

479.5096.9480.5025

EXAMPLE 122 1071

242

1072 Analogouslt to example 106, 67 mg (0.18 mmol) of the azide example 103 were heated under reflux with 21.4 mg (0.25 mmol) of methyl propionate for 20 h. The crude product was triturated with ether. This gave 29.6 mg (36.2%) of the product which was enriched with the main regioisomer (9.3:1 according to NMR). According to LC-MS, the mother liquor contained inter alia more of the regioisomeric product mixture (1:1.82). 1073 MS (ESI): m/z (%)466 MH (100) 1074 Main regioisomer: 1075 1H-NMR (200 MHz, CDCl3): 1.04 (t, 3H, CH3), 1.35 (t, 3H, CH3), 1.59 (t, 3H, CH3), 1.88 (m, 2H, CH2), 3.03 (m, 4H, 2CH2), 3.96 (s, 3H, OCH3), 4.27 (g, 2H, CH2), 5.62 (s, 2H, CH2), 7.08 (d, 1H), 7.43 (dd, 1H), 8.12 (d, 1H), 9.82 (bs, 1H, NH).

EXAMPLE 123 1076

243

1077 Analogously to example 106, 100 mg (0.25 mmol) of the azide example 104 were heated under reflux with 29.9 mg (0.36 mmol) of methyl propionate for 20 h. The precipitated solid was filtered off and washed with ether, giving 47.8 mg (39.6%) of the product in the form of the main regioisomer. According to LC-MS, the mother liquor contained inter alia more reogioisomeric product mixture (1:2.3). 1078 MS (ESI): m/z (%)492 MH (100) 1079 Main reoioisomer: 1080 1H-NMR (200 MHz, CDCl3): 1.32 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.66-2.18 (m, 8H, 4CH2), 3.03 (g, 2H, CH2), 3.62 (m, 1H, CH), 3.95 (s, 3H, OCH3), 4.27 (g, 2H, CH2) 5.63 (s, 2H, CH2), 7.08 (d, 1H) 7.43 (dd, 1H), 8.05 (s, 1H), 8.10 (d, 1H), 9.88 (bs, 1H, NH).

EXAMPLE 24 1081

244

1082 Analogously to example 106, 70 mg (0.17 mmol) of the azide example 106 were reacted with 20.3 mg (0.24 mmol) of methyl propionate. The crude product was recrystallized from ether. This gave 24.5 mg (29.2%) of the main regioisomer. According to LC-MS, the mother liquor contained a mixture of the two regioisomers (15:22). 1083 MS (ESI): m/z (%)506 MH (100) 1084 1H-NMR (200 MHz, CDCl3): 1.22 (t, 3H, CH3), 1.45-2.05 (m, 12H, 6CH2), 2.65 (s, 3H, CH3), 3.48 (m, 1 H, CH), 3.95 (s, 3H, OCH3), 4.27 (g, 2H, CH2), 5.63 (s, 2H, CH2), 7.08 (d, 1H), 7.43 (dd, 1H), 8.05 (s, 1H), 8.10 (d, 1H), 9.87 (bs, 1H, NH).

EXAMPLE 125 1085

245

1086 18.5 mg (0.18 mmol) of N-methylpiperazine were added to a suspension of 20 mg (0.046 mmol) of the phenacyl bromide example 57A in 0.5 ml of 1,2-dichloroethane, and the mixture was heated at 80 C. for 4 h. 0.5 ml of sat. NaHCO3 solution was added afier cooling, and the mixture was worked up by, filtration through 500 mg of Extrelut/500 mg of silica gel (mobile phase:ethyl acetate). The concentrated crude product was purified chromatographically (gradient: CH2Cl2CH2Cl2:MeOH 10:15.1). This gave 18.4 mg (88%) of product. 1087 MS (ESI): m/z (%)453 MH (60) 1088 1H-NMR (200 MHz, CDCL3): 1.05 (t, 3H, CH3), 1.58 ( 3H, CH3), 1.88 (m, 2H, CH2), 2.65 (s, 3H, CH3), 2.75 (s, 3H, CH3), 3.17 (g, 2H, CH2), 3.17-3.25 (m, 8H, 4CH2), 3.98 (s, 2H, CH2), 4.35 (g, 2H, CH2), 7.13 (d, 1H), 8.08 (dd, 1H), 8.70 (d, 1H), 9.57 (bs, 1H, NH)

EXAMPLE 126 1089

246

1090 A suspension of 25 mg (0.057 mmol) of the phenacyl bromide example 57A and 23.8 mg (0.23 mmol) of N-propyl-2-aminoethanol in 0.5 mi of 1,2-dichloromethane was heated at 80 C. for 10 h. 0.5 ml of sat. NaHCO3 solution was added to the reaction mixture, which was then filtered through a biphasic cartridoe (upper phase: 500 mg of Extrelut, 500 mg of silica gel) (mobile phase: ethyl acetate). Concentration gave 23.6 mg of crude product which was purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 9.4 mg (35.8%) of product. 1091 MS (ESI): m/z (%)456 (100) MH1092 1H-NMR (200 MHz, CDCL3): 0.95 (t, 3H, CH3), 1.03 (t, 3H, CH3), 1.43-1.68 (m, 5H), 1.88 (m, 2H), 2.20-2.45 (m, 4H), 2.84 (bd, 2H), 3.02 (t, 2H), 4.25 (g, 2H), 7.03 (d, 1H), 7.75 (dd, 1H), 8.38 (d, 1H), 9.82 (bs, 1H, NH).

EXAMPLE 127 1093

247

1094 27.7 mg (0.37 mmol) of N-methyl-2-aminoethanol were added to a suspension of 40 mg (0.09 mmol) of the phenacyl bromide example 57A in 0.5 ml of 1,2-dichloroethane, and the mixture was healed at 60 C. for 4 h. 1 ml of H2O was added, and the mixture was filered through 1 g of Extrelut (mobile phase: CH2Cl2). The crude product was initial purified chromatographical (gradient: CH2Cl2/MeOH 40:110:1), and the product fraction was purified by preparative thin-layer chromatography (CH2Cl2/MeOH 20:1). This gave 9.5 mg (24.1%) of the desired product as a mixture of the open-chain form 1 and the cyclized form 2. 1095 MS (ESI): m/z (%)428 MH (100) 1096 2: 1H-NMR (200 MHz, CDCl3): 1.03 (t, 3H, CH3), 1.53 (t, 3H, CH3), 1.89 (m, 2H, CH2), 2.22 (t, 2H, CH2), 2.33 (s, 3H, CH3), 2.64 (s, 3H, CH3), 2.78 (bt, 2H, CH2), 3.02 (t, 2H, CH2), 3.87 (dd, 1H), 4.19 (dd, 1H), 4.26 (g, 2H, CH2), 7.03 (d, 1H), 7.75 (dd, 1H), 8.38 (d, 1H), 9.79 (bs, 1H, NH).

EXAMPLE 128 1097

248

1098 0.42 g (4.8 mmol) of morpholine are added to a solution of 1.0 g (2.2 mmol) of the phenacyl bromide example 59A in 10 ml of methylene chloride. After addition of a little methanol, the reaction mixture once more becomes clear. After 2 h of stirring at RT, the mixture is extracted with water and the organic phase is dried over sodium sulfate and concentrated. The residue is purified by silica gel chromatography using methylene chloride/methanol 20:1. 1099 Yield: 0.56 g (55.3%) 1100 1H NMR (300 MHz, CD3OD): 1.47 (t, 3H), 1.56-2.20 (m, 8H), 2.60 (s, 3H), 2.64 (t, 4H), 3.67 (quin., 1H), 3.74 (t, 4H), 3.90 (s, 2H), 4.30 (quart., 2H), 7.28 (d, 1H), 8.25 (dd, 1H), 8.38 (d, 1H).

EXAMPLE 129 1101

249

1102 5.6 mg (0.06 mmol) of Et3N were added to a suspesion of 20 mg (0.05 mmol) of the phenacyl bromide example 57A in 1 ml of triethyl phosphite, and the mixture was stirred at room temperature for 2 h. 0.5 ml of sat. NaHCO3 solution was added, and the mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (mobile phase: ethyll acetate). The mixture was concentrated and purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 7.9 mg (34.9%) of the desired product. 1103 MS (DCI, NH3): m/z (%)491 MH (100) 1104 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.27 (m, 9H, 3CH3), 1.72 (g, 2H, CH2), 2.82 (t, 2H, CH2), 4.13 (m, 6H, 3CH2), 5.07 (t, 1H, CH2P), 5.48 (t, 1H, CH2P), 7.21 (d, 1H), 7.75 (m, 2H).

EXAMPLE 130 1105

250

1106 A solution of 100 mg (0.23 mmol) of the phenacyl bromide example 57A and 31.7 g (0.23 mmol) of thiobenzamide in 3.8 ml of EtOH was heated at 60 C. for 30 min. The product was filtered off with suction and washed with diethyl ether. Concentration under reduced pressure gave 31.1 mg (28.6%) of the desired product. 1107 MS (ESI): m/z472 MH (100) 1108 1H-NMR (200 MHz, D6-DMSO): 0.95 (t, 3H, CH3) 1.34 (t, 3H, CH3); 1.77 (m, 2H, CH2); 2.58 (s, 3H, CH3); 2.99 (t, 3H, CH2); 4.20 (g, 2H, CH2); 7.30 (d, 1H); 7.52 (m, 3H); 8.02 (m, 2H); 8.17 (m, 3H); 12.16 (bs, 1H, NH).

EXAMPLE 131 1109

251

1110 A solution of 30 mg (0.07 mmol) of the phenacyl bromide example 57A and 8.7 mg (0.08 mmol) of 2-methoxyrthioacetamide in 2 ml of isopropanol was heated at 80 C. for 6 h and then concentrated using a rotary evaporator. The crude product was stirred with ether and filtered off with suction. This gave 22.3 mg (73.30%) of the desired product. 1111 MS (DCI, NH3): m/z (%)440 MH (100) 1112 1H-NMR (200 MHz, D6-DMSO): 0.95 (t, 3H, CH3) 1.32 (t, 3H, CH3); 1.78 (m, 2H, CH2); 2.59 (s, 3H, CH3); 3.01 (t, 2H, CH2); 3.43 (s, 3H, OCH3); 4.18 (g, 2H, CH2); 4.77 (s, 2H, CH2); 7.28 (d, 1H); 8,11 (m, 3H); 12.10 (bs, 1H, NH). 1113 In a parallel synthesis, the compounds of the following table were prepared by the following procedure: 0.1 mmol of the thioamide and 32.5 mg (0.075 mmol) of the phenacyl bromide example 57 A in 1 ml of DMF were heated at 70 C. for 2 h and then stirred at RT overnight. 0.5 ml of saturated sodium bicarbonate solution was added to the mixture, which was then filtered through a two-phase cartridge (500 mg of Extrehit/500 mg of silica gel) (mobile phase: ethyl acetate). The filtrate was then concentrated in a Speed-Vac, and the purity was determined by LC-MS. 5MWHPLC area %Ex. No.Structureg/molat 210 nmMz H132

252

409.5137692410 133

253

423.5408580424 134

254

437.5679485438 135

255

477.6332781478 136

256

465.6221284466 137

257

452.5826171453 138

258

460.5618872461 139

259

530.6100779531 140

260

529.6224969530

EXAMPLE 141

2-2-Ethoxy-5-4-(2-aminiothiazole)phenyl-5-methyl-7-propl-3H-imidazo5,1-f-1,2,4triazin-4-one 1114

261

1115 A solution of 40 mg (0.1 mmol) of the phenacyl bromide example 57A in 2 ml of isopropanol was added to 9.13 mg (0.12 mmol) of thiourea, and the mixture was heated at 80 C. for 10 h. 1 ml of H2O was added, and the reaction mixture was then filtered through a cartridge filled with 1 g of Extrelut (upper phase) and 500 mg of SiO2 (mobile phase: ethyl acetate). The filtrate was concentrated under reduced pressure, giving 7.1 mg (18.7% of theory,) of 2-2-ethoxy-5-4-(2-aminothiazole)phenyl-5-methyl-7-propyl-3H-imidazo5,1-f-1,2,4triazin-4-one (77% according to HPLC). 1116 1H-NMR (300 MHz, CD3OD D6-DMSO): 0.97 (t, 3H); 1.42 (t, 3H); 1.82 (m, 2H); 2.57 (s, 3H); 2.95 (t, 2H); 4.17 (dd, 2H); 6.84 (s, 1H); 7.17 (d, 1H); 7.93 (dd, 1H), 8.06 (d, 1H).

EXAMPLE 142 1117

262

1118 66 mg (0.3 mmol) of 3-trifluoromethylphenylthiourea were added to a solution of 100 mg (0.23 mmol) of the phenacyl bromide example 57A in 3 ml of DMF, and the mixture was heated at 40 C. for 16 h. The DMF was condensed off under high vacuum and 1 ml of H2O and CH2Cl2 was added to the residue. The product precipitate that formed was filtered off with suction. This gave 59.6 mg (46.6%) of the desired product. 1119 MS (ESI): m/z (%)555 MH (100) 1120 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3); 1.34 (t, 3H, CH3); 1.78 (m, 2H; CH2) 2.58 (s, 3H, CH3); 2.97 (t, 2H, CH2); 4.18 (g, 2H, CH2); 7.28 (d, 2H); 7.48 (s, 1H); 7.54 (t, 1H); 7.86 (d, 1H); 8.09 (m, 1H); 8.34 (bs, 1H); 10.67 (bs, 1NH); 12.11 (bs, 1H, NH).

EXAMPLE 143 1121

263

1122 Initially, 6.4 mg (0.05 mmol) of N-amidinothiourea were dissolved in 2 ml of hot EtOH and added to a hot solution of 21.4 mg (0.05 mmol) of the phenacyl bromide example 57A in 2 ml of CH3CN, and the mixture was heated under reflux for 3 h. After cooling, 0.7 ml of H2O was added, the mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (mobile phase: 1. ethyl acetate, 2. MeOH), and only the methanol phase was concentrated. The residue was purified by preparative thin-layer chromatography (CH2Cl2:MeOH5:1). This gave 13.6 mg (60.9%) of the desired product. 1123 MS (ESI): m/z (%)453 MH (100) 1124 1H-NMR (300 MHz, D3COD with suppression of water): 0.90 (t, 3H, CH3), 1.35 (t, 3H, CH3), 1.75 (m, 2H, CH2), 2.49 (s, 3H, CH3), 2.90 (t, 2H, CH2), 4.13 (g, 2H, CH2O), 6.90 (s, 1H), 7.10 (d, 1H), 7.89 (dd, 1H), 8.07 (d, 1H).

EXAMPLE 144 1125

264

1126 A solution of 30 mg (0.07 mmol) of the phenacyl bromide example 57A and 12.7 mg (0.08 mmol) of N-benzylthiourea in DMF was initially heated at 60 C. for 3 h, 7 mg (0.07 mmol) of Et3N were then added and the reaction mixture was, after a further 10 min, cooled to room temperature. The DMF was condensed off under high vacuum, 1 ml of sat. NaHCO3 solution was added to the residue and the mixture was filtered through 1 g of Extrelut (mobile phase: CH2Cl2). The crude product was purified chromatographically (ethyl acetate:cyclohexane85:15). This gave 12.9 mg (37.2%) of the desired product. 1127 MS (DCI/NH3): m/z (%)501 MH (100) 1128 1H-NMR (400 MHz, CDCl3): 1.03 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.85 (m, 2H, CH2), 2.65 (s, 3H, CH3), 2.93 (t, 2H, CH2), 4.27 (g, 2H, CH2O), 4.96 (s, 2H, CH2), 5.83 (s, 1H), 6.98 (d, 1H), 7.15-7.29 (m, 6H), 7.99 (d, 1H).

EXAMPLE 145 1129

265

1130 22.9 mg (0.13 mmol) of N-benzoylthiourea were added to a suspension of 50 mg (0.12 mmol) of the phenacyl bromide example 57A in acetone. The mixture was heated at 60 C. and DMF was added until a homogeneous solution was formed. After 20 h, the DMF was condensed off under high vacuum, the residue was triturated with CH2Cl2/ether and the precipitated product was filtered off with suction. This gave 56.7 mg (95%) of the desired product. 1131 MS (ESI): m/z (%)515 MH (100) 1132 1H-NMR (400 MHz, D6-DMSO, with suppression of water): 1.08 (t, 3H, CH3), 1.44 (t, 3H, CH3), 1.94 (m, 2H, CH2), 2.75 (s, 3H, CH3), 3.23 (t, 2H, CH2), 4.25 (g, 2H, CH2O), 7.28 (d, 1H), 7.45 (s, 1H), 7.58 (m, 2H), 7.65 (m, 1H), 8.05 (d, 2H), 8.19 (dd, 1H), 8.24 (d, 1H).

EXAMPLE 146 1133

266

1134 88.6 mg (0.4 mmol) of N-(3-trifluoromethylphenyl)thiourea were added to a solution of 150 mg (0.3 mmol) of the phenacyl bromide example 58A in 3 ml of DMF, and the mixture was heated at 40 C. for 16 h. The DMF was condensed off under high vacuum, 3 ml of H2O were added to the residue and the mixture was filtered through 3 g of Extrelut (mobile phase: CH2Cl2). Chromatographic purification (CH2Cl2CH2Cl2:MeOH50:1) save 182 mg (95%) of the desired product. 1135 MS (ESI): m/z (%) 569 MH (100) 1136 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.25 (t, 3H, CH3), 1.33 (t, 3H, CH3), 1.75 (m, 2H, CH2), 2.89 (2t, 4H, 2CH2), 4.18 (g, 2H, CH2), 7.28 (m, 2H), 7.55 (t, 1H), 7.82 (bd, 1H), 8.05 (m, 2H), 8.38 (bs, 1H), 10.69 (bs, 1H, NH), 11.65 (bs, 1H, NH).

EXAMPLE 147 1137

267

1138 A solution of 150 mg (0.31 mmol) of the phenacyl bromide example 60A and 81.3 mg (0.37 mmol) of N-(3-trifluoromethylphlenyl)thiourea in 3 ml of DMF was heated at 40 C. for 16 h. The volatile components were condensed off under high vacuum and the residue was taken up in 3 ml of H2O and CH2Cl2. The resulting precipitate was filtered off, giving 94.2 mg (49.3%) of the desired product. Another 42 mg (22.4%) of product were isolated from the mother liquor, which was filtered through 3 g of Extrelut (mobile phase: CH2Cl2), concentrated and recrystallized from ether. 1139 MS (ESI): m/z (%)609 MH (100) 1140 1H-NMR (200 MHz, D6-DMSO): 1.33 (t, 3H, CH3), 1.45-2.02 (m, 12H, 6CH2), 3.35 (m, 1H, CH), 4.16 (g, 2H, CH2), 7.27 (m, 2H), 7.40 (s, 1H), 7.54 (t, 1H), 7.82 (d, 1H), 8.05 (m, 2H), 8.39 (bs, 1H), 10.68 (s, 1H, NH), 11.63 (s, 1H, NH).

EXAMPLE 148 1141

268

1142 5.4 l (0.05 mmol) of ethyl oxalyl chloride were added dropwise to a suspension of 20 mg (0.05 mmol) of the aminothiazole example 141 in 1 ml of pyridine, and the mixture was stirred at room temperature for 20 h. The pyridine was condensed off under high vacuum, 0.5 ml of sat. NaHCO3 solution was added to the residue and the mixture was filterred through a two-phase cartridge (500 mg of Extrelut/500 mg of SiO2, mobile phase: ethyl acetate). Recrystallization from ether gave 8.3 mg (33.4) of the desired product. 1143 MS (DCI, NH3): m/z (%)511 MH (100) 1144 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.32 (t, 6H, 2CH3), 1.75 (m, 2H, CH2), 2.84 (t, 2H, CH2), 4.16 (g, 2H, CH2), 4.31 (g, 2H, CH2), 7.26 (d, 1H), 7.75 (s, 1H), 8.08 (m, 2H), 11.65 (bs, 1H, NH), 13.09 (bs, 1H, NH).

EXAMPLE 149 1145

269

1146 5.3 mg (0.05 mmol) of 2-methoxyacetyl chloride were added to a suspension of 20 mg (0.05 mmol) of the aminothiazole example 141 in 1 ml of pyridine. After 20 h, the pyridine was separated off under high vacuum and the crude product was taken up in 0.5 ml of saturated NaHCO3 and filtered through a 2-phase cartridge (500 mg of Extrelut/500 mg of SiO2; mobile phase: ethyl acetate). Crystallization from diethyl ether gave 7 mg (29.8%) of the desired product. 1147 MS (ESI): m/z (%)483 MH (100). 1148 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3); 1.32 (t, 3H, CH3); 1.75 (m, 2H, CH2); 2.52 (s, CH3 under the DMSO signal); 2.85 (t, 2H, CH2); 3.33 (s, 3H, OCH3); 4.16 (m, 4H, 2CH2); 7.23 (d, 1H)); 7.61 (s, 1H); 8.03 (m, 2H); 11.63 (bs, 1H, NH); 12.20 (bs, 1H, NH).

EXAMPLE 150 1149

270

1150 A solution of 30 mg (0.073 mmol) of the aminothiazole example 141 in 0.5 ml of pyridine and 10 mg (0.073 mmol) of 2-acetoxyacetyl chloride was stirred at RT for 4 h. The pyridinie was distilled off under reduced pressure, 0.5 ml of sat. NaHCO3 was added and the reaction mixture was filtered through a two-phase cartridge (upper phase: 500 mg of Extrelut, lower phase: 500 mg of silica gel, mobile phase: ethyl acetate). This gave 30.3 mg (81%) of the desired product in a purity of 84% according to LC-MS. 1151 MS (ESI): m/z (%)511 MH (100) 1152 1H-NMR (200 MHz, CDCl3): 1.02 (t, 3H, CH3); 1.13 (t, 3H, CH3); 1.87 (m, 2H, CH2); 2.29 (s, 3H, CH3); 2.71 (s, 3H, CH3); 3.53 (bt, 2H, CH2); 4.97 (s, 2H, CH2); 6.53 (d, 1H); 7.03 (s, 1H); 7.46 (dd, 1H); 7.72 (d, 1H); 11.67 (bs, 1H, NH); 12.45 (bs, 1 H, NH).

EXAMPLE 151 1153

271

1154 5 g ( 11.54 mmol) of the phenacyl bromide example 57A are suspended in 100 ml of ethanol and cooled to 0 C. Since the suspension is slightly acidic, it is neutralized by addition of a little potassium carbonate. At 0 C., 2.25 g (34.6 mmol) of potassium cyanide in 10 ml of water are added dropwise. After 2 h, the mixture is allowed to warm to RT and stirred at this temperature for 15 h. 300 ml of water are added, the mixture is then extracted 2 with in each case 100 ml of dichloromethane and the combined organic phases are dried (MgSO4) and concentrated using a rotary evaporator. The product is purified by flash chromatography on silica gel (mobile phase: CH2Cl2CH2Cl2/MeOH 100:1CH2Cl2/MeOH 40:1). The product-containing fractions are concentrated and the product is then dissolved in dichloromethane and crystallized by addition of ether. 1155 Yield: 1.78 g (40.6%)

EXAMPLE 152 1156

272

1157 At 0 C., 80.2 mg (1.2 mmol) of NaCN and a crystal of K2CO3 as a solution in 0.4 ml of H2O were added to a suspension of 200 mg (0.41 mmol) of the phenacyl bromide example 60A in 4 ml of ethanol. After 30 min, the mixture was warmed to room temperature and stirred for another 15 h. The mixture was quenched with three times the amount of H2O and then extracted twice with CH2Cl2, and the extract was dried over MgSO4 and concentrated under reduced pressure. This gave 152 mg (86%) of the nitrile. 1158 1H-NMR (200 MHz, CDCl3): 1.62 (t, 3H, CH3), 1.62-2.03 (m, 12H, 6CH2); 2.63 (s, 3H, CH3); 3.42 (m, 1H, CH); 4.08 (s, 2H, CH2); 4.38 (g, 2H, CH2); 7.16 (d, 1H); 8.11 (dd, 1H); 8.69 (d, 1H); 9.61 (bs, 1H, NH).

EXAMPLE 153 1159

273

1160 A solution of 20 mg (0.052 mmol) of the nitrile example 151 in 0.5 ml of glacial acetic acid was heated at 50 C., and 6.8 mg (0.063 mmol) of phenylhydrazine were added dropwise. After 5 h, 1 ml of sat. NaHCO3 solution was added to the reaction mixture, and the mixture was filtered through 1 g of Extrelut (mobile phase: CH2Cl2). Concentration under high vacuum was initially followed by chromatopraphic purification (CH2Cl2:MeOH80:120:1) and then by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 14.6 mg (59%) of the aminopyrrazole. 1161 MS (DCI, NH3): m/z (%)470 (100) MH1162 1H-NMR (200 MHz, CDCl3): 1.07 (t, 3H, CH3); 1.55 (t, 3H, CH3); 1.92 (m, 2H); 2.69 (s, 3H, CH3); 3.19 (t, 2H); 3.92 (bs, 2H, NH2); 4.30 (g, 2H); 5.99 (s, 1H); 7.08 (d, 1H), 7.30-7.70 (m, 5H); 8.03 (dd, 1H); 8.51 (d, 1H); 9.98 (bs, 1H, NH).

EXAMPLE 154 1163

274

1164 In the reaction of example 153, 9.3 mg (34%) of the N-acetylpyrrazole are obtained as a by-product. 1165 LC-MS (ESI): m/z (%)512 (100%) MH1166 1H-NMR (200 MHz, CDCl3): 0.92 (t, 3H, CH3); 1.32 (t, 3H, CH3); 1.74 (dd, 2H); 2.0 (s, 3H, CH3); 2.85 (t, 2H); 4.15 (g, 2H); 6.89 (s, 1H); 7.22 (d, 1H); 7.45-7.62 (m, 6H); 7.9-8.05 (m, 2H); 10.05 (bs, 1H, NH); 11.63 (bs, 1H, NH).

EXAMPLE 155 1167

275

1168 Analogously to example 153, 30 mg (0.08 mmol) of the nitrile example 151 were reacted with 13.5 mg (0.09 mmol) of ethyl 2-hydrazinoacetate at 50 C. After cooling to room temperatur, 20 mg of aldeyde-functionalized Wang resin were added, and the mixture was stirred at 70 C. for 2 h. 0.5 ml of sat. NaHCO3 solution was added, the mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (mobile phase) and the concentrated crude product was initially purified chromatographically (ethyl acetate:cyclohexane5:1) and the product fraction was then purified again by preparative thin-layer chromatography (CH2Cl2:MeOH10:1). This gave 4.1 mg (10.8%) of the desired product, in addition to 3.2 mg (8.4%) of starting material. 1169 MS (ESI): m/z (%)480 MH (100) 1170 1H-NMR (200 MHz, CDCl3): 1.04 (t, 3H, CH3), 1.33 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.89 (m, 2H, CH2), 2.65 (s, 3H, CH3), 3.05 (t, 2H, CH2), 3.75 (bs, 2H, CH2), 4.26 (g, 4H, 2CH2O), 4.86 (s, 2H, NH2), 5.98 (s, 1H), 7.05 (d, 1H), 7.89 (dd, 1H), 8.43 (d, 1H), 9.86 (bs, 1H, NH).

EXAMPLE 156 1171

276

1172 41 l (0.42 mmol) of phenylhydraziie were added dropwise to a solution of 150 mg (0.35 mmol) of the nitrile example 60A in 3 ml of 2M trifluoroacetic acid in CH2Cl2, and the mixture was heated under reflux for 15 h. Addition of 3 ml of sat. NaHCO3 solution and filtration throuhg 3 g of Extrelut (mobile phase: CH2Cl2) gave, after concentration under reduced pressure, the crude product, which was purified chromatographically (gradient: CH2Cl2CH2Cl2/MeOH50:1). This gave 149 mg (82%) of the desired product (91.3% pure according to HPLC). 1173 MS (DCI, NH3): m/z (%)524 MH (100) 1174 1H-NMR (200 MHz, CDCL3): 1.60 (t, 3H, CH3), 1.67 (bs, 6H,3CH2), 1.82-2.17 (m, 6H, 3CH2), 2.76 (s, 3H, CH3), 3.63 (m, 1H, CH), 4.35 (g, 2H, CH2) 5.95 (s, 1H), 6.62 (bs, 2H, NH2), 7.12 (d, 1H), 7.36-7.68 (m, 5H, phenyl), 8.02 (dd, 1H), 8.63 (d, 1H), 10.54 (bs, 1H, NH).

EXAMPLE 157 1175

277

1176 At room temperature, 23.1 mg (0.21 mmol) of methoxyacetyl chloride were added to a solution of 100 mg (0.21 mmol) of the aminopyrrazole example 153 in 2 ml of pyridine, and the mixture was stirred for 1 h. The pyridine was condensed off under high vacuum. 0.5 ml of sat. NaHCO3 solution was added to the residue and the resulting precipitate was dissolved using ethyl acetate. The mixture was filtered through 500 mg of Extrelut/500 mg of SiO2 (mobile phase: ethyl acetate), and the crude product was recrystallized from ethyl acetate/ether. This gave 14.8 mg (12.8%) of the desired product. A further 55 mg (47.7%) were obtained by recrystallization of the product which precipitated on the cartridge during filtration. 1177 MS (ESI): m/z (%)542 MH (100) 1178 1H-NMR (200 MHz, D6-DMSO): 0.94 (t, 3H, CH3), 1.33 (t, 3H, CH3), 1.74 (m, 2H, CH2), 2.86 (t, 2H, CH2), 3.32 (s, 3H, OCH3), 3.98 (s, 2H, CH2), 4.18 (g, 2H, CH2O), 6.91 (s, 1H), 7.25 (d, 1H), 7.35-7.63 (m, 5H), 8.00 (m, 2H), 9.93 (bs, 1H, NH), 11.62 (bs, 1H, NH).

EXAMPLE 158 1179

278

1180 Analogously to example 157, 25 mg (0.053 mmol) of the aminopyrrazole example 153 were reacted in 0.5 ml of pyridine with 7.3 mg (0.053 mmol) of ethyl oxalyl chloride at room temperature for 4 h. Chromatographic purification (gradient: CH2Cl2CH2Cl2:MeOH50:1) gave 21.8 mg (71.9%) of the desired product. 1181 MS (ESI): m/z (%)570 MH (100) 1182 1H-NMR (200 MHz, CDCl3): 1.05 (t, 3H, CH3), 1.43 (t, 3H, CH3), 1.58 (t, 3H, CH3), 1.90 (m, 2H, CH2), 2.65 (s, 3H, CH3), 3.04 (t, 2H, CH2), 4.30 (g, 2H, CH2O), 4.42 (g, 2H, CH2O), 7.11 (d, 1H), 7.21 (s, 1H), 7.45-7.65 (m, 5H), 8.05 (dd, 1H), 8.60 (d, 1H), 9.24 (bs, 1H, NH), 9.79 (bs, 1H, NH).

EXAMPLE 159 1183

279

1184 Analogously to example 157, 200 mg (0.43 mmol) of the aminopyrrazole example 153 in 4 ml of pyridine were reacted with 58.1 mg (0.43 mmol) of 2-acetoxyacetyl chloride. The crude product was triturated with ether, giving 158 mg (65.1%) of the desired product. 1185 MS (ESI): m/z (%)570 MH (100) 1186 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.33 (t, 3H, CH3), 1.74 (m, 2H, CH2), 2.11 (s, 3H, CH3), 2.53 (s, 3H, CH3), 2.85 (t, 2H, CH2), 4.17 (g, 2H, CH2), 4.65 (s, 2H, CH2), 6.92 (s, 1H), 7.25 (d, 1H), 7.35-7.60 (m, 5H), 7.99 (m 2H), 10.25 (bs, 1H, NH), 11.63 (bs, 1H, NH).

EXAMPLE 160 1187

280

1188 7.9 mg (0.19 mmol) of LiOH were added to a solution of 90 mg (0.16 mmol) of the amidopyrrazole example 159 in 2 ml of THF/H2O (1:1), and the mixture was stirred at room temperature for 30 min. The mixture was diluted with 1 ml of H2O and filtered through 3 g of Extrelut (mobile phase: CH2Cl2). The crude product was recrystalized from CH2Cl2, giving 49 mg (58.8%) of the desired product. 1189 MS (ESI): m/z (%)528 MH (100) 1190 1H-NMR (200 MHz, D6-DMSO): 0.93 (t, 3H, CH3), 1.32 (m, 3H, CH3), 1.75 (m, 2H, CH2), 2.84 (t, 2H, CH2), 3.95 (s, 2H, CH2), 4.15 (g, 2H, CH2), 6.91 (s, 1H), 7.22 (d, 1H), 7.33-7.68 (m, 5H), 7.98 (m, 2H).

EXAMPLE 161 1191

281

1192 Analogously to example 156, 25 mg (0.068 mmol) of the nitrile example 151 were stirred with 14.3 mg (0.081 mmol) of 3-trifluorophenylhydrazine and 0.27 ml (0.135 mmol) of a 0.5 M solution of trifluoroacetic acid in 1,2-dichloroethane at room temperature for 20 h. 0.5 ml of sat. NaHCO3 solution was added and the mixture was filtered through 0.5 g of Extrelut/0.5 g of SiO2 (mobile phase: ethyl acetate), and the crude product was then dissolved in 0.5 ml of pyrrdine, and 157 l (0.018 mmol) of 2-methoxyacetyl chloride were added. After 3 h at room temperature, another 1 ml of sat. NaHCO, was added, the mixture was filtered through 1 g of Extrelut (mobile phase: CH2Cl2) and the filtrate was concentrated under reduced pressure. Purification by thin-layer chromatography (CH2Cl2:MeOH20.1) gave 4.5 mg (40.1%) of the desired product (90% pure according to HPLC). 1193 MS (ESI): m/z (%)610 MH (100) 1194 1H-NMR (200 MHz, CDCl3): 1.05 (t, 3H, CH3); 1.57 (t, 3H, CH3); 1.90 (m, 2H, CH2); 2.67 (s, 3H; CH3); 3.07 (t, 2H, CH2); 3.47 (s, 3H, OCH3); 4.06 (s, 2H; CH2); 4.32 (g, 2H, CH2); 7.05-7.13 (m, 2H); 7.61-7.87 (m, 4H); 8.03 (dd, 1H); 8.59 (d, 1H); 8.68 (bs, 1H, NH); 9.88 (bs, 1H, NH). 1195 The compounds of the table below were prepared in a parallel synthesis analogously to example 161 from the nitrile example 151, the appropriate hydrazine and 2-methoxyacetyl chloride. 6HPLCMWarea %Ex. No.Structureg/molat 210 nmMz H162

282

518.5881519.5802 163

283

547.5472548.5416 164

284

551.6187552.6074 165

285

605.7967606.787 166

286

576.0662577.06 167

287

610.5076611.505

EXAMPLE 168

2-(2-Ethoxy-5-(2-oxiranyl)phenyl)-5-methyl-7-n-propyl-3H-imidazo5,1-f1,2,4-triazin-4-one 1196

288

1197 57 mg (1.5 mmol) of NaBH4 (evolution of gas) and 1 ml of 2 N NaOH were added to a suspension, cooled to 20 C., of 500 mg (1.12 mmol) of the phenacyl bromide example 57A in 2 ml of THF. The frozen solution was warmed to 0 C. and stirred for 30 min. Addition of 10% strength acetic acid (strong evolution of gas) and two extractions wvith ethyl acetate gave, after drying of the extracts over MgSO4 and concentration under reduced pressure, the crude product, which was purified chromatographically (gradienit: CH2Cl2:MeOH from 100% to 100:150:130:1). The product fraction was concentrated and then triturated with ether, giving 221.7 mg (54.2%) of the epoxide. 1198 MS (DCI, NH3): m/z (%)355 MH (57) 1199 1H-NMR (300 MHz, D3COD): 0.98 (t, 3H, CH3), 1.44 (t, 3H, CH3), 1.83 (m, 2H, CH2), 2.57 (s, 3H, CH3), 3.98 (t, 2H, CH2), 3.55-3.75 (m, 2H), 4.19 (g, 2H, CH2), 4.87 (m, 1H), 7.17 (d, 1H), 7.58 (dd, 1H), 7.78 (d, 1H).

EXAMPLE 169

2-(2-Ethoxy-5-(2-oxiranyl)phenyl)-5-methyl-7-cycloheptyl-3H-imidazo5,1-f1,2,4-triazin-4-one 1200

289

1201 20.2 mg (0.53 mmol) of NaBH4 (evolution of gas) and 2 ml of N NaOH solution were added to a suspension, cooled to 20 C., of 200 mg (0.41 mmol) of the phenacyl bromide example 60A in 0.8 ml of EtOH/0.8 ml of THF. The mixture was allowed to warnm to 0 C. and, after 30 min a 10% strength solution of glacial acetic acid was added (strong evolution of gas), the mixture was extracted with ethyl acetate and the extract was dried over MgSO4. The mixture was concentrated and the residue was purified chromatographically (gradient: CH2Cl2:MeOH50:1). This gave 29 mg (17.3%) of the desired product and 104 mg (54%) of the ring-openinig product example 170. 1202 MS (DCI, NH3): m/z (%)409 MH (53) 1203 1H-NMR (400 MHz, D3COD): 1.43 (t, 3H, CH3), 1.55-2.05 (m, 12H, 6CH2), 2.57 (s, 3H, CH3), 3.45 (m, 1H, CH), 3.71 (2dd, 2H), 7.17 (d, 1H), 7.57 (dd, 1H), 7.78 (d, 1H).

EXAMPLE 170 1204 Ring-opening product: 290

1205 MS (DCI, NH3): m/z (%)469 MH (100) 1206 1H-NMR (400 MHz, D3COD): 1.43 (t, 3H, CH3), 1.55-2.05 (m, 12H, 6CH2), 2.57 (s, 3H, CH3), 3.45 (m, 1H, CH), 3.74 (dd, 1H), 3.83 (dd, 1H), 4.19 (g, 2H, CH2O), 5.78 (dd, 1H, CH), 7.16 (d, 1H), 7.52 (dd, 1H), 7.71 (d, 1H).

EXAMPLE 171 1207

291

1208 0.6 ml (5.6 mmol) of tert-butylamine was added to a suspension of 100 mg (0.282 mmol) of the epoxide example 168 in 2.5 ml of isopropanol, and the mixture was heated under reflux for 30 h. The reaction mixture was concentrated and purified by flash charomatography (gradient: CH2Cl2CH2Cl2/MeOH10:1). This gave 105 mg of a mixture of two regioisomers which were separated by preparative HPLC. 1209 42 mg (35%) as second fraction 1210 1H-NMR (200 MHz, CDCL3): 1.02 (t, 3H, CH3), 1.12 (s, 9H, C(CH3)3), 1.54 (t, 3H, CH3), 1.88 (m, 2H, CH2), 2.59 (dd, 1H), 2.64 (s, 3H, CH3), 2.93 (dd, 1H), 3.01 (t, 2, CH2), 4.25 (g, 2H, CH2), 4.61 (dd, 1H), 7.02 (d, 1H), 8.11 (d, 1H).

EXAMPLE 172 1211

292

1212 In the reaction example 171, as first fraction, 9 mg (7.5%) of the regioisomer are obtained as by-product. 1213 1H-NMR (200 MHz, CDCL3): 1.03 (t, 3H, CH3), 1.07 (s, 9H, C(CH3)3), 1.57 (t, 3H, CH3), 1.89 (m, 2H, CH2), 2.63 (s, 3H, CH3), 3.03 (t, 2H, CH2), 3.32 (dd, 1H), 3.61 (dd, 1H), 4.36 (dd, 1H), 4.25 (g, 2H, CH2), 7.01 (d, 1H), 7.44 (dd, 1H), 8.08 (d, 1H).

EXAMPLE 173 1214

293

1215 Analogously to example 171, 100 mg (0.28 mmol) of the epoxide example 168 were heated under reflux with 0.91 ml (5.6 mmol) of 1-phenyl-3-butylamine in 2.5 ml of isopropanol for 24 h. After concentration under reduced pressure, the two regioisomers were separated by preparative chromatography. 1216 This gives 51.8 mg (36.5%) as second fraction 1217 MS (ESI): m/z (%)504 MH (100) 1218 1H-NMR (200 MHz, CDCL3): 1.02 (t, 3H, CH3), 1.15 (d, 3H, CH3), 1.56 (t, 3H, CH3), 1.62-1.95 (m, 4H, 2CH2), 2.64 (s, 3H, CH3), 2.68 (m, 2H), 3.01 (m, 3H), 4.25 (g, 2H, CH2), 4.64 (dd, 1H, CHO), 7.03 (d, 1H), 7.12-7.33 (m, 5H, phenyl), 7.53 (dd, 1H), 8.09 (d, 1H)

EXAMPLE 174 1219

294

1220 In the reaction example 173, as first fraction, 21.4 mg (15.1%) of the regioisomer are obtained as a by-product. 1221 MS (ESI): m/z (%)504 MH (100) 1222 1H-NMR (200 MHz, CDCL3): 0.93-1.13 (m, 9H, 3CH3), 1.57 (t, 3H, CH3), 1.63-1.97 (m, 4H, 2CH2), 2.65 (m, 3H, CH3), 2.65 (m, 1H, CH), 2.99 (g, 2H, CH3), 3.42-3.75 (m, 2H), 3.92 (m, 1H), 4.25 (g, 2H, CH2), 7.01 (d, 1H), 7.05-7.44 (m, 6H), 8.04 (dd, 1H), 9.90 (bs, 1H, NH)

EXAMPLE 175 1223

295

1224 Analogously to example 171, 100 mg (0.28 mmol) of the epoxide example 168 were reacted with 0.48 ml (5.6 mmol) of isopropylamine. After chromatographic pre-purification (gradoemt: CH2Cl2CH2Cl2/MeOH10:1), 77.9 mg (67%) of the regioisomer mixture were separated by preparative HPLC. 1225 10 mg (8.6%) are obtained as second fraction. 1226 MS (ESI): m/z (%)4.14 MH (65) 1227 1H-NMR (200 MHz, CDCL3): 1.03 (t, 3H, CH3), 1.09 (d, 6H. 2CH3), 1.55 (t, 3H, CH3), 1.88 (m, 2H, CH2), 2.64 (s, 3H, CH3), 2.66 (dd, 1H,), 2.88 (m, 1H, CH), 2.95 (m, 3H, CH, CH2), 4.25 (g, 2H, CH2), 4.69 (dd, 1H), 7.03 (d, 1H), 7.52 (dd, 1H), 8.09 (d, 1H).

EXAMPLE 176 1228

296

1229 In the reaction example 175, as first fraction, 20 mg (8.6%) of the regioisomer are obtained as a by-product. 1230 MS (ESI): m/z (%)414 MH (65) 1231 1H-NMR (200 MHz, CDCL3): 1.04 (t, 3H, CH3), 1.07 (2d, 6H, 2CH3), 1.55 (t, 3H, CH3), 1.88 (m, 2H, CH2), 2.62 (s, 3H, CH3), 2.75 (m, 1H, CH), 3.02 (t, 2H, CH2), 3.49 (dd, 1H), 3.72 (dd, 1H), 3.94 (dd, 1H), 4.25 (g, 2H, CH2), 7.03 (d, 1H), 7.43 (dd, 1H), 8.04 (d, 1H)

EXAMPLE 177 AND EXAMPLE 178 1232

297

1233 A solution of 20 mg (0.05 mmol) of the epoxide example 169 and 589 mg (0.98 mmol) of isopropylamine in 0.5 ml of isopropanol was heated at 80 C. for 20 h. The mixture was concentrated and the residue wvas then purified by preparative thin-layer chromatography. This gave 15 mg (65.5%) of the desired product as a mixture of two regioisomers. 1234 MS (DCI, NH3): m/z (%)468 MH (100) 1235 Main regioisomer: 1236 1H-NMR (400 MHz, CDCl3): 1.25 (2d, 6H, 2CH3), 1.55 (t, 3H, CH3), 1.57-2.10 (m, 12H, 6CH2), 2.64 (s, 3H, CH3), 2.83 (dd, 1H), 3.08 (m, 2H), 3.43 (m, 1H, CH), 4.23 (g, 2H, CH2O), 4.95 (dd, 1H, CH), 7.01 (d, 1H), 7.55 (dd, 1H), 8.10 (d, 1H). 1237 2nd Regioisomer: 1238 1H-NMR (400 MHz, CDCl3): 1.12 (2d, 6H, 2CH3), 1.53 (t, 3H, CH3), 1.57-2.10 (m, 12H, 6CH2), 3.43 (m, 1H, CH), 3.62 (dd, 1H), 3.75 (dd, 1H), 4.00 (dd, 1H), 4.23 (g, 2H, CH2O), 7.03 (d, 1H), 7.50 (dd, 1H), 8.06 (d, 1H).

EXAMPLE 179

2-(2-Ethoxy-5-carboxylphenyl)-5-methyl-7-n-propyl-3H-imidazo5,1-f1,2,4-triazine-4-one 1239

298

1240 1.1 g (6.9 mmol) of bromine, dropwise, and then 1 g (2.3 mmol) of the phenacyl bromide example 57A, a little at a time, were added at 10 C. to a solution of 1.8 g (46 mmol) of NaPH in 10 ml of H2O. The mixture was allowed to slowly warm to room temperature and, after 2 h, diluted with water and extracted once with CH2Cl2. The aqueous phase was then acidified (pH 1) and extracted twice with CH2Cl2 and five times with ethyl acetate. The organic phase was dried over MgSO4 and concentrated under reduced pressure, and the residue was purified chromatographically (gradient: CH2Cl2CH2Cl2:MeOH20:1). The product fraction was once more triturated with CH2Cl2. This gave 146 mg (17.8%) of the desired product. 1241 MS (DCI, NH3): m/z (%)357 MH (100) 1242 1H-NMR (200 MHz, D6-DMSO): 0.94 (t, 3H, CH3), 1.35 (t, 3H, CH3), 1.75 (m, 2H, CH2), 2.84 (t, 2H, CH2), 4.18 (g, 2H, CH2), 7.25 (d, 1H), 7.99 (dd, 1H), 8.10 (d, 1H), 11.62 (bs, 1H, NH), 12.92 (bs, 1H, COOH).

EXAMPLE 180 1243

299

1244 5.1 mg (0.04 mmol) of N-ethylpiperazine. 18 mg (0.06 mmol) of o-(benzotriazol-1-yl)-N,N,N,N-tetramethyluronium tetrafluoroborate (TBTU) and 10.8 mg of N-ethyldiisopropylamine were added to a solulion of 20 mg (0.06 mmol) of the carboxylic acid example 179 in 2 ml of DMF, and the mixture was stirred at room temperature for 1 h. The DMF was condensed off under high vacuum, 0.5 ml of water were added to the residue and the mixture was filtered through a two-phase cartridge (500 mg of Extrelut/500 mg of SiO2, mobile phase: 1. ethyl acetate, 2. CH2Cl2:MeOH10:1) The CH2Cl2/MeOH phase was concentrated, and the residue was separated by preparative thin-layer chromatooraphy. This gave 245 mg (96.5%) of the desired product. 1245 MS (DCI, NH3): m/z (%)453 MH (100) 1246 1H-NMR (400 MHz, D3COD): 0.98 (t, 3H, CH3), 1.13 (t, 3H, CH3), 1.45 (t, 3H, CH3), 1.82 (m, 2H), 2.48 (g, 2H, CH2), 2.53 (bs, 4H, 2CH2), 2.57 (s, 3H, CH3), 2.95 (t, 2H, CH2), 3.45 (m, 4H, 2CH2), 4.25 (g, 2H, CH2), 7.23 (d, 1H), 7.63 (dd, 1H), 7.78 (d, 1H).

EXAMPLE 181 1247

300

1248 20 mg (0.06 mmol) of the carboxylic acid example 179 and 5.4 mg (0.06 mmol) of morpholine were added to a suspension, cooled to 0 C., of 77.8 mg (0.06 mmol) of polymer-bound N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) in 3 ml of CHCl3. The mixture was allowed to warm to room temperature overnight and then heated under reflux for 20 h. 1 ml of sat. NaHCO solution was added and the mixture was fillered through 1 g of Extrelut (mobile phase: CH2Cl2). The concentrated residue was purified by preparative thin-layer chromatography (CH2Cl2:MeOH20:1). This gave 3.5 mg (14.7%) of the desired product. 1249 MS (ESI): m/z (%)426 MH (100) 1250 1H-NMR (200 MHz, CDCl3): 1.03 (t, 3H, CH3), 1.59 (t, 3H, CH3), 1.87 (m, 2H, CH2), 2.64 (s, 3H, CH3), 2.99 (t, 2H, CH2), 3.55-3.81 (m, 8H, 4CH2), 4.31 (g, 2H, CH2O), 7.10 (d, 1H), 7.62 (dd, 1H), 8.25 (d, 1H), 9.89 (bs, 1H, NH).

EXAMPLE 182 1251

301

1252 Analogously to example 181, 10 mg (0.03 mmol) of the carboxylic acid example 179 were reacted with 3.1 mg (0.031 mmol) of N-methylpiperazine and 38.4 mg (0.038 mmol) of polymer-bound EDC. Preparative thin-layer chromatography (CH2Cl2:MeOH10:1) gave 4.2 mg (34.1%) of the desired product. 1253 MS (ESI): m/z (%)439 MH (38) 1254 1H-NMR (200 MHz, CDCl3): 1.02 (t, 3H, CH3), 1.59 (t, 3H, CH3), 1.85 (m, 2H, CH2), 2.34 (s, 3H, CH3), 2.48 (bs, 4H, 2CH2), 2.63 (s, 3H, CH3), 3.00 (t, 2H, CH2), 3.65 (bm, 4H, 2CH2), 4.31 (g, 2H, CH2), 7.09 (d, 1H), 7.60 (dd, 1H), 8.24 (d, 1H), 9.83 (bs, 1H, NH).

EXAMPLE 183 1255

302

1256 1.7 ml of a 0.1 M solution of SmJ2 (0.17 mmol) in THF were added to a solution of 50 mg (0.12 mmol) of the phenacyl bromide example 57A, and the mixture was heated under reflux for 20 h. Two more times, in each case after 24 h, 1.7 ml of SmJ2 solution were added. Cooling and filtration through 500 mg of silica gel gave 60 mg of crude product which was purified chromatographically (gradient: CH2Cl2CH2Cl2/MeOH 100:150:1). This gave 27.6 mng (67.5%) of the desired product 1257 (81% according to LC-MS) 1258 MS (ESI): m/z (%)355 MH (100) 1H-NMR (200 MHz, CDCl3): 1.05 (t, 3H, CH3), 1.59 (t, 3H, CH3), 1.91 (m, 2H, CH2), 2.63 (s, 3H, CH3), 2.64 (s, 3H, CH3), 3.02 (t, 2H, CH2), 4.33 (g, 2H, CH2), 7.11 (d, 1H) 8.12 (dd, 1H), 8.72 (d, 1H), 9.64 (bs, 1H, NH)

EXAMPLE 184 1259

303

1260 Analogously to example 183, 50 mg (0.10 mmol) of the phenacyl bromide example 60A were heated under reflux with 5.1 ml (0.51 mmol) of a 0.1 M solution of SmI2 in THF for 10 h. Purification by thin-layer chromatography (CH2Cl2:MeOH20:1) gave 14.4 mg (34.4%) of the desired product (94.1% according to HPLC). 1261 MS (ESI) m/z (%)409 MH (100) 1262 1H-NMR (200 MHz, CDCL3). 1.59 (t, 3H, CH3), 1.60-2.10 (m, 12H, 6CH2), 2.63 (s, 6H, 2CH3), 3.43 (m, 1H, CH), 4.33 (g, 2H, CH2), 7.11 (d, 1H), 8.12 (dd, 1H), 8.72 (d, 1H), 9.82 (bs, 1H, NH)

EXAMPLE 185 1263

304

1264 A suspension of 180 mg of the epoxide example 40A (0.44 mmol) in 3.5 ml of isopropanol is slowly added to a solution of 1.9 ml of isopropylamine (21.9 mmol) in 1.5 ml of isopropanol. Immediately. a clear yellow solution is formed. After stirring overnight, the precipitated solid is filtered off with suction, washed with a little isopropanol and with petroleum ether and dried under high vacuum. 1265 Yield: 83.6 mg (39.9% of theory) 1266 MS (DCI, NH3): m/z (%)470 (MH) (100) 1267 1H-NMR (400 MHz, D4-MeOD): 1.11 (t, 6H); 1.42 (t, 3H); 1.70-1.78 (m, 2H), 1.86-1.95 (m, 4H); 2.10-2.18 (m, 2H); 2.58 (s, 3H); 2.69 (dd, 1H); 2.85-2.90 (m, 2H); 3.66 (qui, 1H); 3.96-4.07 (m, 3H); 4.14 (2H); 7.09-7.17 (m, 2H); 7.38 (d, 1H).

EXAMPLE 186 1268

305

1269 tert-Buttlamine (2.6 ml, 25 mmol) is initially charged in 1.5 ml of isopropanol, and the mixture is cooled to 0 C. A suspension of 205 mg of the epoxide example 40A (0.5 mmol) and 3.5 ml of isopropanol is then added. With stirring, the mixture is allowed to warm to room temperature and then stirred overnight. The mixture is concentrated using a rotary evaporator and the residue is purified by column chromatography using dichloromethane/methanol/ammonia solution 95:5:1. 1270 Yield: 177 mg (73% of theory) 1271 MS (ESI-pos): m/z (%)484 (MH) (100), 428 (68), 325 (21) 1272 1H-NMR (400 MHz, D4-MeOD): 1.15 (s, 9H); 1.42 (t, 3H); 1.68-1.78 (m, 2H); 1.85-1.98 (m, 4H); 2.07-2.16 (m, 2H); 2.55 (s, 3H); 2.68-2.81 (m, 2H); 3.55 (qui, 1H); 3.95-4.05 (m, 3H); 4.14 (q, 2H); 7.09-7.17 (2H); 7.48 (d, 1H).

EXAMPLE 187 1273

306

1274 A suspension of 205 mg of the epoxide example 40A (0.5 mmol) in 3.5 ml of isopropanol is added to an ice-cooled soluion of 1-methyll-3-phenylpropylaamine (1.2 ml, 7.5 mmol) in 1.5 ml of isopropanol. With stirring, the mixture is allowed to warm to room temperature and then stirred ovenight. Following concentration, the crude product is purified by column chromatography using dichloromethane/methanol/ammonia solution 97:3:1. The product fractions are concentrated using a rotary evaporator and the resulting residue is crystallized with ether. The product is filtered off with suction and dried under high vacuum. 1275 Yield: 192 mg (67.7% of theory) 1276 MS (DCI, NH3): m/z (%)560 (MH) (100) 1277 1H-NMR (200 MHz, D4-MeOD): 1.15 (d, 3H); 1.42 (t, 3H); 1.55-2.20 (m, 10H); 2.55-3.92 (m, 9H); 3.65 (qui, 1H); 3.98-4.20 (m, 5H); 7.06-7.27 (m, 6H); 7.38 (d, 1H).