RELATED APPLICATIONS

This application claims benefit under 35 U.S.C. 119(e) of U.S. provisional application Ser. No. 60/560,239 filed Apr. 7, 2004, from German application number DE102004 012676.3 filed Mar. 16, 2004, from German application number DE102004040168.3 filed Aug. 18, 2004, from German application number DE102004061145.9 filed Dec. 16, 2004, and from European application EP05002628.5, filed Feb. 9, 2005, the contents of which are incorporated herein.

DESCRIPTION OF THE INVENTION

The present invention relates to glucopyranosyl-substituted benzene derivatives of general formula I

[Image Omitted]
wherein the groups R¹to R⁶and R^7a, R^7b, R^7care as defined hereinafter, including the tautomers, the stereoisomers, the mixtures thereof and the salts thereof. The invention further relates to pharmaceutical compositions containing a compound of formula I according to the invention as well as the use of a compound according to the invention for preparing a pharmaceutical composition for the treatment of metabolic disorders. In addition, the invention relates to processes for preparing a pharmaceutical composition as well as a compound according to the invention.

In the literature, compounds which have an inhibitory effect on the sodium-dependent glucose cotransporter SGLT2 are proposed for the treatment of diseases, particularly diabetes.

Glucopyranosyloxy-substituted aromatic groups and the preparation thereof and their possible activity as SGLT2 inhibitors are known from published International applications WO 98/31697, WO 01/27128, WO 02/083066, WO 03/099836, WO 2004/063209, WO 2004/080990, WO 2004/013118, WO 2004/052902, WO 2004/052903 and US application U.S. 2003/0114390.

AIM OF THE INVENTION

The aim of the present invention is to find new pyranosyloxy-substituted benzene derivatives, particularly those which are active with regard to the sodium-dependent glucose cotransporter SGLT, particularly SGLT2. A further aim of the present invention is to discover pyranosyloxy-substituted benzene derivatives which have an enhanced inhibitory effect on the sodium-dependent glucose cotransporter SGLT2 in vitro and/or in vivo compared with known, structurally similar compounds and/or have better pharmacological or pharmacokinetic properties.

A further aim of the present invention is to provide new pharmaceutical compositions which are suitable for the prevention and/or treatment of metabolic disorders, particularly diabetes.

The invention also sets out to provide a process for preparing the compounds according to the invention.

Other aims of the present invention will become apparent to the skilled man directly from the foregoing and following remarks.

OBJECT OF THE INVENTION

In a first aspect the present invention relates to glucopyranosyloxy-substituted benzene derivatives of general formula I

[Image Omitted]
wherein

R¹is selected from the definitions of the group A and
- if R³is selected from the definitions of the group B, R¹may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C_1-4-alkyl, C_2-4-alkenyl-C_1-4-alkyl, C_2-4-alkynyl-C_1-4-alkyl, C_2-4-alkenyl-C_1-4-alkoxy, C_2-4-alkynyl-C_1-4-alkoxy, C_3-7-cycloalkyl-C_1-4-alkyl, C_5-7-cycloalkenyl-C_1-4-alkyl, a methyl group substituted by 1 to 3 fluorine atoms, an ethyl group substituted by 1 to 5 fluorine atoms, C_1-4-alkoxy, a methoxy group substituted by 1 to 3 fluorine atoms, an ethoxy group substituted by 1 to 5 fluorine atoms, a C_1-4-alkyl group substituted by a hydroxy or C_1-3-alkoxy group, a C_2-4-alkoxy group substituted by a hydroxy or C_1-3-alkoxy group, C_3-6-cycloalkyl-C_1-3-alkoxy or hydroxy,
- while in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O or CO, and
R²denotes hydrogen, fluorine, chlorine, bromine, hydroxy, C_1-4-alkyl, C_1-4-alkoxy, cyano or nitro, while the alkyl or alkoxy group may be mono- or polysubstituted by fluorine, and
R³is selected from the definitions of the group B and
- if R¹is selected from the definitions of the group A, R³may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C_1-6-alkyl, C_2-4-alkenyl-C_1-4-alkyl, C_2-4-alkynyl-C_1-4-alkyl, C_2-4-alkenyl-C_1-4-alkoxy, C_2-4-alkynyl-C_1-4-alkoxy, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, C_3-7-cycloalkyl-C_1-4-alkyl, C_5-7-cycloalkenyl-C_1-4-alkyl, C_3-6-cycloalkylidenmethyl, hydroxy, C_1-6-alkoxy, C_3-6-cycloalkyl-C_1-3-alkoxy, aryl, aryl-C_1-3-alkyl, heteroaryl, heteroaryl-C_1-3-alkyl, aryloxy, aryl-C_1-3-alkyl-oxy, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, a C_2-4-alkyl or C_2-4-alkoxy group substituted by 1 to 5 fluorine atoms, a C_1-4-alkyl group substituted by a cyano group, a C_1-4-alkyl group substituted by a hydroxy or C_1-3-alkyloxy group, cyano, carboxy, C_1-3-alkoxycarbonyl, aminocarbonyl, (C_1-3-alkylamino)carbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-yl-carbonyl, 4-(C_1-3-alkyl)-piperazin-1-ylcarbonyl, (C_1-4-alkyl)carbonylamino, C_1-4-alkyl-sulphonylamino, C_1-4-alkylsulphanyl, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, arylsulphonylamino, aryl-C_1-3-alkylsulphonylamino or arylsulphonyl,
R⁴, R⁵independently of one another denote hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, C_1-3-alkyl, C_1-3-alkoxy, methyl or methoxy substituted by 1 to 3 fluorine atoms,
A denotes C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, aryl, heteroaryl, C_1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C_1-4-alkyl)piperazin-1-ylcarbonyl, arylamino-carbonyl, heteroarylaminocarbonyl, C_1-4-alkoxycarbonyl, aryl-C_1-3-alkoxycarbonyl, heteroaryl-C_1-3-alkoxycarbonyl, amino, C_1-4-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)piperazin-1-yl, C_1-4-alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, aryloxy, heteroaryloxy, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, heteroarylsulphanyl, heteroarylsulphinyl, heteroarylsulphonyl, cyano or nitro,
- while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and
- the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and
- the above-mentioned cycloalkyl and cycloalkenylrings independently of one another may be mono- or disubstituted by substituents selected from fluorine and C_1-3-alkyl, and
- in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N,
B denotes tri-(C₄-alkyl)silyl-C_1-6-alkyl, C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, amino, C_1-3-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)piperazin-1-yl, arylcarbonylamino, heteroarylcarbonylamino, nitro, C_3-10-cycloalkyloxy, C_5-10-cycloalkenyloxy, C_3-10-cycloalkylsulphanyl, C_3-10-cycloalkylsulphinyl, C_3-10-cycloalkylsulphonyl, C_5-10-cycloalkenylsulphanyl, C_5-10-cycloalkenylsulphinyl, C_5-10-cycloalkenyl-sulphonyl, arylsulphanyl, arylsulphinyl, heteroarylsulphanyl or heteroarylsulphinyl,
- while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and
- the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1;
- while the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
- in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N,
R^Ndenotes H, C_1-4-alkyl, C_1-4-alkylcarbonyl or C_1-4-alkylsulphonyl,
L1 independently of one another are selected from among hydroxy, cyano, nitro, C_3-7-cycloalkyl, aryl, heteroaryl, C_1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)-aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, C_1-4-alkoxycarbonyl, aryl-C_1-3-alkoxycarbonyl, heteroaryl-C_1-3-alkoxycarbonyl, C_1-4-alkyloxy, aryloxy, heteroaryloxy, C_1-4-alkylsulphanyl, arylsulphanyl, heteroarylsulphanyl, C_1-4-alkylsulphinyl, arylsulphinyl, heteroarylsulphinyl, C_1-4-alkylsulphonyl, arylsulphonyl and heteroarylsulphonyl; and
L2 independently of one another are selected from among fluorine, chlorine, bromine, iodine, C_1-3-alkyl, difluoromethyl, trifluoromethyl, C_1-3-alkoxy, difluoromethoxy, trifluoromethoxy and cyano; and
R⁶, R^7a, R^7b, R^7cindependently of one another have a meaning selected from among hydrogen, (C_1-18-alkyl)carbonyl, (C_1-8-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C_1-3-alkyl)-carbonyl,
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups which may be mono- or disubstituted independently of one another by identical or different groups L2; and
by the heteroaryl groups mentioned in the definition of the above groups are meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl, isoquinolinyl or tetrazolyl group,
or is meant a pyrrolyl, furanyl, thienyl or pyridyl group, wherein one or two methyne groups are replaced by nitrogen atoms,
or is meant an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms,
while the above-mentioned heteroaryl groups independently of one another may be mono- or disubstituted by identical or different groups L2;
while, unless otherwise stated, the above-mentioned alkyl groups may be straight-chain or branched,
the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof.

The compounds of general formula I according to the invention and the physiologically acceptable salts thereof have valuable pharmacological properties, particularly an inhibitory effect on the sodium-dependent glucose cotransporter SGLT, particularly SGLT2. Moreover compounds according to the invention may have an inhibitory effect on the sodium-dependent glucose cotransporter SGLT1. Compared with a possible inhibitory effect on SGLT1 the compounds according to the invention preferably inhibit SGLT2 selectively.

The present invention also relates to the physiologically acceptable salts of the compounds according to the invention with inorganic or organic acids.

This invention also relates to pharmaceutical compositions, containing at least one compound according to the invention or a physiologically acceptable salt according to the invention, optionally together with one or more inert carriers and/or diluents.

This invention also relates to the use of at least one compound according to the invention or one of the physiologically acceptable salts thereof for preparing a pharmaceutical composition which is suitable for the treatment or prevention or diseases or conditions which can be influenced by inhibiting the sodium-dependent glucose cotransporter SGLT, particularly SGLT2.

This invention also relates to the use of at least one compound according to the invention or one of the physiologically acceptable salts thereof for preparing a pharmaceutical composition for inhibiting the sodium-dependent glucose cotransporter SGLT, particularly SGLT2.

The invention further relates to a process for preparing a pharmaceutical composition according to the invention, characterised in that a compound according to the invention or one of the physiologically acceptable salts thereof is incorporated in one or more inert carriers and/or diluents by a non-chemical method.

The present invention also relates to a process for preparing the compounds of general formula I according to the invention, characterised in that

a) in order to prepare compounds of general formula I which are defined as hereinbefore and hereinafter,
a compound of general formula II

[Image Omitted]
wherein

Râ€² denotes H, C_1-4-alkyl, (C_1-18-alkyl)carbonyl, (C_1-18-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C_1-3-alkyl)-carbonyl, wherein the alkyl or aryl groups may be mono- or polysubstituted by halogen;
R^8a, R^8b,
R^8c, R^8dindependently of one another have one of the meanings given hereinbefore and hereinafter for the groups R⁶, R^7a, R^7b, R^7c, denote a benzyl group or a R^aR^bR^cSi group or a ketal or acetal group, particularly an alkylidene or arylalkylidene ketal or acetal group, while in each case two adjacent groups R^8a, R^8b, R^8c, R^8dmay form a cyclic ketal or acetal group or a 1,2-di(C_1-3-alkoxy)-1,2-di(C_1-3-alkyl)-ethylene bridge, while the above-mentioned ethylene bridge forms, together with two oxygen atoms and the two associated carbon atoms of the pyranose ring, a substituted dioxane ring, particularly a 2,3-dimethyl-2,3-di(C_1-3-alkoxy)-1,4-dioxane ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C_1-3-alkoxy and benzyl groups may also be substituted by a di-(C_1-3-alkyl)amino group; and
R^a, R^b, R^cindependently of one another denote C_1-4-alkyl, aryl or aryl-C_1-3-alkyl, wherein the aryl or alkyl groups may be mono- or polysubstituted by halogen;
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups;
and wherein the groups R¹to R⁵and R⁶, R^7a, R^7b, R^7care defined as hereinbefore and hereinafter;
is reacted with a reducing agent in the presence of a Lewis or BrÃ¸nsted acid, while the any protective groups present are cleaved simultaneously or subsequently; or
b) in order to prepare compounds of general formula I wherein R⁶, R^7a, R^7band R^7cdenote hydrogen,
a compound of general formula III

[Image Omitted]

wherein R^8a, R^8b, R^8c, R^8dand R¹to R⁵are defined as hereinbefore and hereinafter, but at least one of the groups R^8a, R^8b, R^8c, R^8ddoes not denote hydrogen, is hydrolysed, and
if desired a compound of general formula I thus obtained wherein R⁶denotes a hydrogen atom, is converted by acylation into a corresponding acyl compound of general formula I, and/or
if necessary any protective group used in the reactions described above is cleaved and/or
if desired a compound of general formula I thus obtained is resolved into its stereoisomers and/or
if desired a compound of general formula I thus obtained is converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts thereof.

This invention further relates to a process for preparing compounds of general formula II

[Image Omitted]
wherein

Râ€² denotes H, C_1-4-alkyl, (C_1-8-alkyl)carbonyl, (C_1-8-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C_1-3-alkyl)-carbonyl, wherein the alkyl or aryl groups may be mono- or polysubstituted by halogen;
R^8a, R^8b,
R^8c, R^8dindependently of one another has one of the meanings given for the groups R⁶, R^7a, R^7b, R^7c, denote a benzyl group or a R^aR^bR^cSi group or a ketal or acetal group, while in each case two adjacent groups R^8a, R^8b, R^8c, R^8dmay form a cyclic ketal or acetal group or may form, with two oxygen atoms of the pyranose ring, a substituted 2,3-oxydioxane ring, particularly a 2,3-dimethyl-2,3-di(C_1-3-alkoxy)-1,4-dioxane ring, and alkyl, aryl and/or benzyl groups may be mono- or polysubstituted by halogen or C_1-3-alkoxy and benzyl groups may also be substituted by a di-(C_1-3-alkyl)amino group; and
R^a, R^b, R^cindependently of one another denote C_1-4-alkyl, aryl or aryl-C_1-3-alkyl, while the alkyl or aryl groups may be mono- or polysubstituted by halogen;
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, preferably phenyl groups;
and R¹to R⁵, R⁶, R^7a, R^7b, R^7care defined as hereinbefore and hereinafter,
wherein an organometallic compound (V) which may be obtained by halogen-metal exchange or by inserting a metal in the carbon-halogen bond of a halogen-benzylbenzene compound of general formula IV

[Image Omitted]
wherein Hal denotes Cl, Br and I and R¹to R⁵are defined as hereinbefore and hereinafter, and optionally subsequent transmetallation, is added to a gluconolactone of general formula VI

[Image Omitted]
wherein R^8a, R^8b, R^8c, R^8dare defined as hereinbefore and hereinafter, and
then the resulting adduct, is reacted, preferably in situ, with water or an alcohol Râ€²â€”OH, while Râ€² denotes optionally substituted C_1-4-alkyl, in the presence of an acid, such as for example methanesulphonic acid, sulphuric acid, hydrochloric acid, acetic acid or ammonium chloride, and optionally the product obtained in the reaction with water wherein Râ€² denotes H is converted, in a subsequent reaction, with an acylating agent, such as for example the corresponding acid chloride or anhydride, into the product of formula II wherein Râ€² denotes (C_1-18-alkyl)carbonyl, (C_1-18-alkyl)oxycarbonyl, arylcarbonyl or aryl-(C_1-3-alkyl)-carbonyl, which may be substituted as specified.

The intermediate products listed, particularly those of formula IV, formula II and formula III, are also a subject of this invention.

DETAILED DESCRIPTION OF THE INVENTION

Unless otherwise stated, the groups, residues and substituents, particularly R¹to R⁵, A, B, L1, L2, R^N, R⁶, R^7a, R^7b, R^7c, R^8a, R^8b, R^8c, R^8d, are defined as above and hereinafter.

If residues, substituents or groups occur several times in a compound, they may have the same or different meanings.

According to the invention preferred glucopyranosyl-substituted benzene derivatives are those of general formula I

[Image Omitted]
wherein

R¹is selected from the definitions of the group A and
- if R³is selected from the definitions of the group B, R¹may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C_1-4-alkyl, C_2-4-alkenyl-C_1-4-alkyl, C_2-4-alkynyl-C_1-4-alkyl, C_3-7-cycloalkyl-C_1-4-alkyl, C_5-7-cycloalkenyl-C_1-4-alkyl, a methyl group substituted by 1 to 3 fluorine atoms, an ethyl group substituted by 1 to 5 fluorine atoms, C_1-4-alkoxy, a methoxy group substituted by 1 to 3 fluorine atoms, an ethoxy group substituted by 1 to 5 fluorine atoms, a C_1-4-alkyl group substituted by a hydroxy or C_1-3-alkoxy group, a C_2-4-alkoxy group substituted by a hydroxy or C_1-3-alkoxy group, C_3-6-cycloalkyl-C_1-3-alkoxy or hydroxy,
- while in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O or CO, and
R²denotes hydrogen, fluorine, chlorine, bromine, hydroxy, C_1-4-alkyl, C_1-4-alkoxy, cyano or nitro, while the alkyl or alkoxy group may be mono- or polysubstituted by fluorine, and
R³is selected from the definitions of the group B and
- if R¹is selected from the definitions of the group A, R³may additionally also be selected from the meanings hydrogen, fluorine, chlorine, bromine, iodine, C_1-6alkyl, C_2-4-alkenyl-C_1-4-alkyl, C_2-4-alkynyl-C_1-4-alkyl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, C_3-7-cycloalkyl-C_1-4-alkyl, C_5-7-cycloalkenyl-C_1-4-alkyl, C_3-6-cycloalkylidenemethyl, hydroxy, C_1-6-alkoxy, C_3-6-cycloalkyl-C_1-3-alkoxy, aryl, aryl-C_1-3-alkyl, heteroaryl, heteroaryl-C_1-3-alkyl, aryloxy, aryl-C_1-3-alkyl-oxy, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, a C_2-4-alkyl or C_2-4-alkoxy group substituted by 1 to 5 fluorine atoms, a C_1-4-alkyl group substituted by a cyano group, a C_1-4-alkyl group substituted by a hydroxy or C_1-3-alkyloxy group, cyano, carboxy, C_1-3-alkoxycarbonyl, aminocarbonyl, (C_1-3-alkylamino)carbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-yl-carbonyl, 4-(C_1-3-alkyl)-piperazin-1-ylcarbonyl, (C_1-4-alkyl)carbonylamino, C_1-4-alkyl-sulphonylamino, C_1-4-alkylsulphanyl, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, arylsulphonylamino, aryl-C_1-3-alkylsulphonylamino or arylsulphonyl,
R⁴, R⁵independently of one another denote hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, C_1-3-alkyl, C_1-3-alkoxy, methyl or methoxy substituted by 1 to 3 fluorine atoms,
A denotes C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, aryl, heteroaryl, C_1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C_1-4-alkyl)piperazin-1-ylcarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, C_1-4-alkoxycarbonyl, aryl-C_1-3-alkoxycarbonyl, heteroaryl-C_1-3-alkoxycarbonyl, amino, C_1-4-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)-piperazin-1-yl, C_1-4-alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, aryloxy, heteroaryloxy, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, arylsulphonyl, heteroarylsulphanyl, heteroarylsulphinyl, heteroarylsulphonyl, cyano or nitro,
- while the above-mentioned alkynyl- and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and
- while the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and
- the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
- in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N,
B denotes tri-(C_1-4-alkyl)silyl-C_1-6-alkyl, C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, amino, C_1-3-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)piperazin-1-yl, arylcarbonylamino, heteroarylcarbonylamino, nitro, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl, arylsulphanyl, arylsulphinyl, heteroarylsulphanyl or heteroarylsulphinyl,
- while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, and
- the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1;
- the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
- in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N,
R^Ndenotes H or C_1-4-alkyl,
L1 independently of one another are selected from among cyano, nitro, aryl, heteroaryl, C_1-4-alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, C_1-4-alkoxycarbonyl, aryl-C_1-3-alkoxycarbonyl, heteroaryl-C_1-3-alkoxycarbonyl, C_1-4-alkyloxy, aryloxy, heteroaryloxy, C_1-4-alkylsulphanyl, arylsulphanyl, heteroarylsulphanyl, C_1-4-alkylsulphinyl, arylsulphinyl, heteroarylsulphinyl, C_1-4-alkylsulphonyl, arylsulphonyl and heteroarylsulphonyl; and
L2 independently of one another are selected from among fluorine, chlorine, bromine, iodine, C_1-3-alkyl, difluoromethyl, trifluoromethyl, C_1-3-alkoxy, difluoromethoxy, trifluoromethoxy and cyano; and
R⁶, R^7a,
R^7b, R^7cindependently of one another have a meaning selected from among hydrogen, (C_1-8-alkyl)carbonyl, (C_1-8-alkyl)oxycarbonyl, arylcarbonyl and aryl-(C_1-3-alkyl)-carbonyl,
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono- or disubstituted independently of one another by identical or different groups L2; and
by the heteroaryl groups mentioned in the definition of the above groups are meant a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group,
or is meant a pyrrolyl, furanyl, thienyl or pyridyl group, wherein one or two methyne groups are replaced by nitrogen atoms,
or is meant an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms,
while the above-mentioned heteroaryl groups may be mono- or disubstituted independently of one another by identical or different groups L2;
while, unless otherwise stated, the above-mentioned alkyl groups may be straight-chain or branched,
the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof.

Some preferred meanings of individual groups and substituents of the compounds according to the invention will be given hereinafter.

The group R³is preferably in the meta or para position to the â€”CH₂bridge, so that compounds according to the following formulae I.1 and I.2, particularly formula I.2, are preferred:

[Image Omitted]

The term aryl appearing in the groups L1, R¹, R³, A and B preferably denotes phenyl.

The term heteroaryl occurring in the groups L1, R¹, R³, A and B preferably denotes pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiazolyl or thiadiazolyl.

The group A preferably denotes C_2-4-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, C_1-4-alkylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C_1-4-alkyl)piperazin-1-ylcarbonyl, C_1-4-alkoxycarbonyl, amino, C_1-4-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)piperazin-1-yl, C_1-4-alkylcarbonylamino, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cyclo-alkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl, cyano and nitro,

while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, preferably fluorine, and
the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and
the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N, preferably O or CO, most particularly preferably by O.

Particularly preferably, the group A denotes C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_1-4-alkylsulphinyl, C_1-4-alkylsulphonyl, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl, cyano and nitro,

while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, preferably fluorine, and
the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1, and
the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
in the above-mentioned C_5-6-cycloalkyl rings a methylene group may be replaced by O.

Most particularly preferably, the group A denotes C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyl, C_3-7-cycloalkyloxy, cyano, while in C_5-6-cycloalkyl groups a methylene unit may be replaced by O.

Examples of the most particularly preferred definitions of the group A are ethynyl, prop-1-yn-1-yl, but-1-yn-1-yl, cyano, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy.

The group B preferably denotes tri-(C_1-4-alkyl)silyl-C_1-6-alkyl, C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, amino, C_1-3-alkylamino, di-(C_1-3-alkyl)amino, pyrrolidin-1-yl, pyrrolidin-2-on-1-yl, piperidin-1-yl, piperidin-2-on-1-yl, morpholin-4-yl, morpholin-3-on-4-yl, piperazin-1-yl, 4-(C_1-3-alkyl)piperazin-1-yl, nitro, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl,

while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, preferably fluorine, and
the above-mentioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1;
the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N, preferably O, CO, S, SO₂or NR^N, most particularly preferably by O or CO.

Particularly preferably the group B denotes tri-(C_1-4-alkyl)silyl-C_1-6-alkyl, C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, nitro, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_3-7-cycloalkylsulphanyl, C_3-7-cycloalkylsulphinyl, C_3-7-cycloalkylsulphonyl, C_5-7-cycloalkenylsulphanyl, C_5-7-cycloalkenylsulphinyl, C_5-7-cycloalkenylsulphonyl,

while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or chlorine, preferably fluorine, and
the above-m entioned alkynyl and alkenyl groups may be mono- or disubstituted by identical or different groups L1;
while the above-mentioned cycloalkyl and cycloalkenyl rings may be mono- or disubstituted independently of one another by substituents selected from fluorine and C_1-3-alkyl, and
in the above-mentioned cycloalkyl and cycloalkenyl rings one or two methylene groups may be replaced independently of one another by O, S, CO, SO, SO₂or NR^N, preferably O, CO, S, SO₂or NR^N, most particularly preferably by O or CO.

Most particularly preferably the group B denotes tri-(C_1-4-alkyl)silyl-C_1-6-alkyl, C_2-6-alkyn-1-yl, C_2-6-alken-1-yl, C_3-7-cycloalkyloxy, C_5-7-cycloalkenyloxy, C_3-7-cycloalkylsulphanyl, C_5-7-cycloalkenylsulphanyl, while the above-mentioned alkynyl and alkenyl groups may be mono- or polysubstituted by fluorine or monosubstituted by chlorine or the group L1, and in the cycloalkyl and cycloalkenyl groups one or two methylene groups may be replaced independently of one another by O, CO, S, SO₂or NR^N, particularly O or CO.

Examples of most particularly preferred definitions of the group B are trimethylsilylethyl, ethynyl, 1-propyn-1-yl, 1-butyn-1-yl, tert.-butylethynyl, 2-hydroxyprop-2-ylethynyl, 2-methoxyprop-2-ylethynyl, 3-hydroxy-1-propyn-1-yl, 3-methoxy-1-propyn-1-yl, ethenyl, 1-propenyl, 1-butenyl, tert.-butylethenyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuranyloxy, tetrahydrothiophenyloxy, 1,1-dioxotetrahydrothiophenyloxy, tetrahydropyranyloxy, tetrahydrothiopyranyloxy, 1,1-dioxotetrahydrothiopyranyloxy, tetrahydrofuranonyloxy, piperidinyloxy, piperidinonyloxy, pyrrolidin-3-yloxy, pyrrolidinon-3-yloxy, tetrahydrofuranyl-sulphanyl, cyclopropylsulphanyl, cyclobutylsulphanyl, cyclopentyl-sulphanyl and cyclohexylsulphanyl, while the â€”NH group in a piperidinyl, piperidinonyl, pyrrolidinyl or pyrrolidinonyl ring may be substituted by R^N, particularly C_1-3-alkyl or acetyl.

Most particularly preferred meanings are trimethylsilylethyl, ethynyl, 2-hydroxyprop-2-ylethynyl, 2-methoxyprop-2-ylethynyl, 3-hydroxy-1-propyn-1-yl, 3-methoxy-1-propyn-1-yl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, piperidin-4-yloxy, N-methylpiperidin-4-yloxy and N-acetylpiperidin-4-yloxy. Examples which deserve special mention are ethynyl, trimethylsilylethyl, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuran-3-yloxy and tetrahydropyran-4-yloxy.

If in the residues or groups A, B, R¹or R³there are cycloalkyl or cycloalkenyl rings wherein two methylene groups are replaced by O, S or NR^Nor are replaced by S, NR^N, CO, SO or SO₂, these methylene groups are preferably not directly connected to one another. If however two methylene groups are replaced by O and CO or by NR^Nand CO, these may be directly connected to one another, so as to form a â€”Oâ€”COâ€” or â€”NR^Nâ€”CO group.

Preferred meanings of the group L1 are selected from among hydroxy, cyano, C_3-6-cycloalkyl, C_1-4-alkylcarbonyl, aminocarbonyl, C_1-4-alkylaminocarbonyl, di-(C_1-3-alkyl)aminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, C_1-4-alkoxycarbonyl, C_1-4-alkyloxy, C_1-4-alkylsulphanyl, C_1-4-alkylsulphinyl, and C_1-4-alkylsulphonyl.

Particularly preferred meanings of the group L1 are selected from among hydroxy, C_1-4-alkyloxy and C_1-4-alkylsulphanyl.

If L1 denotes hydroxy, the hydroxy group is not directly linked to a C atom of a double or triple bond.

Compounds according to a first embodiment of this invention may be described by general formula I, particularly formulae I.1 and I.2, particularly preferably formula I.2, wherein

R³is selected from one of the definitions of the group B given hereinbefore and
the other groups and substituents are defined as hereinbefore and hereinafter,
including the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof.

According to this embodiment preferred meanings of the group R¹are hydrogen, fluorine, chlorine, bromine, iodine, C_1-4-alkyl, C_2-6-alkynyl, C_1-4-alkoxy, C_2-4-alkenyl-C_1-4-alkoxy, C_2-4-alkynyl-C_1-4-alkoxy, methyl substituted by 1 to 3 fluorine atoms, ethyl substituted by 1 to 5 fluorine atoms, methoxy substituted by 1 to 3 fluorine atoms, ethoxy substituted by 1 to 5 fluorine atoms, C_1-4-alkyl substituted by a hydroxy or C_1-3-alkoxy group, C_2-4-alkoxy substituted by a hydroxy or C_1-3-alkoxy group, C_2-6-alkenyl, C_3-6-cycloalkyl, C_3-6-cycloalkyl-C_1-3-alkyl, C_3-7-cycloalkyloxy, C_3-6-cycloalkyl-C_1-3-alkoxy, C_5-7-cycloalkenyloxy, hydroxy, amino, nitro or cyano, while in the C_5-6-cycloalkyl groups a methylene group may be replaced by O.

Particularly preferred meanings are hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, isopropyl, difluoromethyl, trifluoromethyl, ethynyl, prop-1-yn-1-yl, but-1-yn-1-yl, hydroxy, methoxy, ethoxy, difluoromethoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, particularly methyl and chlorine.

Compounds according to a second embodiment of this invention may be described by general formula I, particularly formulae I.1 and I.2, particularly preferably formula I.2, wherein

R¹is selected from the definitions of the group A given hereinbefore and
the other groups and substituents are defined as hereinbefore and hereinafter,
including the tautomers, the stereoisomers thereof, the mixtures thereof and the salts thereof.

According to this second embodiment preferred meanings of the group R³are hydrogen, fluorine, chlorine, bromine, hydroxy, cyano, C_1-6-alkyl, trimethylsilylethyl, C_2-6-alkenyl, C_2-6-alkynyl, difluoromethyl, trifluoromethyl, C_3-7-cycloalkyl, C_5-7-cycloalkenyl, C_1-6-alkyloxy, difluoromethoxy, trifluoromethoxy, pentafluorethoxy, C_3-7-cycloalkyloxy, tetrahydrofuranyloxy, tetrahydrofuranonyloxy, C_1-6-alkylsulphanyl, cyclopropylidenemethyl, aryl or heteroaryl.

According to this second embodiment particularly preferred meanings of the group R³are hydrogen, fluorine, chlorine, methyl, ethyl, isopropyl, tert.-butyl, ethynyl, 1-propynyl, trimethylsilylethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, isopropoxy, cyclopentyloxy, difluoromethoxy, trifluoromethoxy, pentafluorethoxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-on-3-yloxy, methylsulphanyl, ethylsulphanyl, isopropylsulphanyl, cyclopropylidenemethyl, phenyl, fluorophenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiazolyl or thiadiazolyl.

According to this second embodiment most particularly preferred meanings of the group R³are hydrogen, fluorine, chlorine, methyl, ethyl, isopropyl, tert.-butyl, ethynyl, 1-propynyl, trimethylsilylethyl, difluoromethyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, isopropoxy, cyclopentyloxy, difluoromethoxy, trifluoromethoxy, pentafluorethoxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-on-3-yloxy, methylsulphanyl, ethylsulphanyl, isopropylsulphanyl, cyclopropylidenemethyl. Examples of such particularly preferred meanings are methyl, ethyl, methoxy, ethoxy, trimethylsilylethyl, ethynyl, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-on-3-yloxy, particularly trimethylsilylethyl, ethoxy, cyclopentyloxy and tetrahydrofuran-3-yloxy.

Meanings of other groups and substituents will now be given which are to be regarded as preferred according to general formula I, formulae I.1 and I.2 and also according to the embodiments described hereinbefore:

Preferred meanings of the group R²are hydrogen, fluorine, chlorine, bromine, methyl, hydroxy, methoxy, ethoxy, trifluoromethoxy, cyano, nitro and methyl substituted by 1 to 3 fluorine atoms.

Particularly preferred meanings of the group R²are hydrogen, fluorine, hydroxy, methoxy, ethoxy and methyl, particularly hydrogen and methyl.

Preferred meanings of the group R⁴are hydrogen and fluorine, particularly hydrogen.

Preferred meanings of the group R⁵are hydrogen and fluorine, particularly hydrogen.

The group R^Npreferably denotes H, methyl, ethyl or acetyl.

The group R⁶preferably denotes according to the invention hydrogen, (C_1-8-alkyl)oxycarbonyl, C_1-8-alkylcarbonyl or benzoyl, particularly hydrogen or (C_1-6-alkyl)oxycarbonyl, C_1-6-alkylcarbonyl, particularly preferably hydrogen, methylcarbonyl, methoxycarbonyl or ethoxycarbonyl, most particularly preferably hydrogen or methoxycarbonyl.

The substituents R^7a, R^7b, R^7cpreferably represent independently of one another hydrogen, (C_1-8-alkyl)oxycarbonyl, (C_1-18-alkyl)carbonyl, benzoyl, particularly hydrogen or (C_1-6-alkyl)oxycarbonyl, (C_1-8-alkyl)carbonyl, particularly preferably hydrogen, methoxycarbonyl, ethoxycarbonyl, methylcarbonyl or ethylcarbonyl. Most particularly preferably R^7a, R^7band R^7crepresent hydrogen.

The compounds of formula I wherein R⁶, R^7a, R^7band R^7caccording to the invention have a meaning other than hydrogen, for example C_1-8-alkylcarbonyl, are preferably suitable as intermediate products for the synthesis of compounds of formula I wherein R^7a, R^7band R^7cdenote hydrogen.

Particularly preferred compounds of general formula I are selected from among formulae I.2a to I.2d, particularly I.2c:

[Image Omitted]
while the groups R¹to R⁶and R^7a, R^7b, R^7chave one of the meanings given previously, particularly have one of the meanings given specified as being preferred; and particularly

R¹denotes hydrogen, fluorine, chlorine, bromine, iodine, C_1-4-alkyl, C_2-6alkynyl, C_1-4-alkoxy, C_2-4-alkenyl-C_1-4-alkoxy, C_2-4-alkynyl-C_1-4-alkoxy, methyl substituted by 1 to 3 fluorine atoms, ethyl substituted by 1 to 5 fluorine atoms, methoxy substituted by 1 to 3 fluorine atoms, ethoxy substituted by 1 to 5 fluorine atoms, C_1-4-alkyl substituted by a hydroxy or C_1-3-alkoxy group, C_2-4-alkoxy substituted by a hydroxy or C_1-3-alkoxy group, C_2-6-alkenyl, C_3-6-cycloalkyl, C_3-6-cycloalkyl-C_1-3-alkyl, C_3-7-cycloalkyloxy, C_3-6-cycloalkyl-C_1-3-alkoxy, C_5-7-cycloalkenyloxy, hydroxy, amino, nitro or cyano, while in the C_5-6-cycloalkyl groups a methylene group may be replaced by O; particularly preferably denotes hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, isopropyl, difluoromethyl, trifluoromethyl, ethynyl, prop-1-yn-1-yl, but-1-yn-1-yl, hydroxy, methoxy, ethoxy, difluoromethoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy or cyclohexyloxy; and
R²denotes hydrogen, fluorine, hydroxy, methoxy, ethoxy or methyl, particularly hydrogen or methyl; and
R³is selected from the group B consisting of trimethylsilylethyl, ethynyl, 1-propyn-1-yl, 1-butyn-1-yl, tert.-butylethynyl, 2-hydroxyprop-2-ylethynyl, 2-methoxyprop-2-ylethynyl, 3-hydroxy-1-propyn-1-yl, 3-methoxy-1-propyn-1-yl, ethenyl, 1-propenyl, 1-butenyl, tert.-butylethenyl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuranyloxy, tetrahydrothiophenyloxy, 1,1-dioxotetrahydrothiophenyloxy, tetrahydropyranyloxy, tetrahydrothiopyranyloxy, 1,1-dioxotetrahydrothiopyranyloxy, tetrahydrofuranonyloxy, piperidinyloxy, piperidinonyloxy, pyrrolidin-3-yloxy, pyrrolidinone-3-yloxy, tetrahydrofuranyl-sulphanyl, cyclopropylsulphanyl, cyclobutylsulphanyl, cyclopentylsulphanyl and cyclohexylsulphanyl, while the â€”NH group in a piperidinyl, piperidinonyl, pyrrolidinyl or pyrrolidinonyl ring may be substituted by R^N, particularly C_1-3-alkyl or acetyl; is particularly preferably selected from trimethylsilylethyl, ethynyl, 2-hydroxyprop-2-ylethynyl, 2-methoxyprop-2-ylethynyl, 3-hydroxy-1-propyn-1-yl, 3-methoxy-1-propyn-1-yl, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, piperidin-4-yloxy, N-methylpiperidin-4-yloxy and N-acetylpiperidin-4-yloxy; and
R⁴denotes hydrogen or fluorine, particularly hydrogen; and
R⁵denotes hydrogen or fluorine, particularly hydrogen; and
R⁶denotes hydrogen, (C_1-6-alkyl)oxycarbonyl, (C_1-6-alkyl)carbonyl or benzoyl, particularly hydrogen, methylcarbonyl, methoxycarbonyl or ethoxycarbonyl, most particularly preferably hydrogen; and
R^7a, R^7b, R^7cindependently of one another represent hydrogen, (C_1-6-alkyl)oxycarbonyl, (C_1-8-alkyl)carbonyl or benzoyl, particularly hydrogen, methoxycarbonyl, ethoxycarbonyl, methylcarbonyl or ethylcarbonyl, particularly preferably hydrogen;
including the tautomers, the stereoisomers, the mixtures thereof and the salts thereof.

According to a variant of the embodiments given hereinbefore, other preferred compounds are those wherein the phenyl group which carries the substituent R³has at least one other substituent R⁴and/or R⁵which is different from hydrogen. According to this variant, particularly preferred compounds are those which have a substituent R⁴representing fluorine.

The phenyl group which carries the substituent R³is preferably at most monofluorinated.

The compounds of general formula I specified in the experimental section that follows, and the derivatives thereof, wherein R⁶has a meaning according to the invention other than hydrogen, particularly wherein R⁶denotes ethoxycarbonyl or methoxycarbonyl, including the tautomers, the stereoisomers thereof and the mixtures thereof, are preferred according to the invention.

Particularly preferred compounds of general formula I are selected from among:

(1) 1-chloro-2-(4-cyclopentyloxybenzyl)-4-(Î²-D-glucopyranos-1-yl)-benzene
(2) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-((R)-tetrahydrofuran-3-yloxy)-benzyl]-benzene
(3) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene
(4) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-(tetrahydrofuran-2-on-3-yloxy)-benzyl]-benzene
(5) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-(4-cyclobutyloxy-benzyl)-benzene
(6) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-(4-cyclohexyloxy-benzyl)-benzene
(7) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-(tetrahydropyran-4-yloxy)-benzyl]-benzene
(8) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-(1-acetyl-piperidin-4-yloxy)-benzyl]-benzene
(10) 1-(Î²-D-Glucopyranos-1-yl)-4-methyl-3-[4-(tetrahydrofuran-3-yloxy)-benzyl]-benzene
(11) 1-(Î²-D-Glucopyranos-1-yl)-4-methyl-3-[4-(2-trimethylsilyl-ethyl)-benzyl]-benzene
(12) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene
(13) 1-chloro-4-(Î²-D-glucopyranos-1-yl)-2-[4-(piperidin-4-yloxy)-benzyl]-benzene
(14) 1-fluoro-4-(Î²-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene
(15) 1-(Î²-D-glucopyranos-1-yl)-3-(4-ethynyl-benzyl)-benzene
(16) 1-ethynyl-4-(Î²-D-glucopyranos-1-yl)-2-(4-ethoxy-benzyl)-benzene
(17) 1-methoxy-4-(Î²-D-glucopyranos-1-yl)-2-(4-ethynyl-benzyl)-benzene
and the derivatives thereof wherein R⁶has a meaning according to the invention other than hydrogen, particularly wherein R⁶denotes ethoxycarbonyl or methoxycarbonyl,
including the tautomers, the stereoisomers thereof and the mixtures thereof.

In the processes according to the invention the groups R¹, R², R³, R⁴and R⁵preferably have the meanings specified hereinbefore as being preferred. Moreover Râ€² preferably denotes H, C_1-3-alkyl or benzyl, particularly H, ethyl or methyl. The groups R^8a, R^8b, R^8cand R^8dindependently of one another preferably denote H, C_1-4-alkylcarbonyl or benzyl, particularly H, methylcarbonyl, ethylcarbonyl or benzyl.

The invention also relates to compounds of general formula IV, particularly of general formula IVâ€²

[Image Omitted]
wherein Hal denotes chlorine, bromine or iodine and the groups R¹, R², R⁴and R⁵are as hereinbefore defined and the group R³is selected from the group B, as intermediate products or starting materials in the synthesis of the compounds according to the invention. Particularly preferably, the groups R¹, R², R³, R⁴and R⁵have the meanings given after formulae I.2a to I.2d. Most particularly preferred are compounds of general formula IVâ€², wherein Hal denotes chlorine, bromine or iodine and the groups R¹, R², R⁴and R⁵have the meanings given after formulae I.2a to I.2d and the group R³denotes ethynyl or C_3-6-1-alkyn-1-yl, while the ethynyl group may be substituted by the group â€”SiR₃, while the groups R independently of one another represent C_1-4-alkyl, C_1-4-alkoxy or aryl, and the C_3-6-1-alkyn-1-yl group may be substituted by hydroxy or C_1-3-alkoxy, particularly hydroxy or methoxy.

The invention also relates to