Patent ID: 6509341
Filing Date: 2003-01-21
Classification: A61P,C07D

Abstract:
A carboxylic acid of formula I whereR1 is tetrazole or a group â€ƒand R denotes a) a radical OR9 where R9 is: hydrogen, the cation of an alkali metal, the cation of an alkaline earth metal or a physiologically tolerated organic ammonium ion; C3-C8-cycloalkyl, C1-C8-alkyl, CH2-phenyl which is unsubstituted or substituted, C3-C6-alkenyl or a C3-C6-alkynyl group which is unsubstituted or substituted, or phenyl which is unsubstituted or substituted; b) a 5-membered heteroaromatic system linked via a nitrogen atom; c) a group â€ƒwhere k has a value of 0, 1 or 2, p has a value of 1, 2, 3 or 4, and R10 is C1-C4-alkyl, C3-C8-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl or unsubstituted or substituted phenyl; d) a radical â€ƒwhere R11 is C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, which radicals are unsubstituted or carry a C1-C4-alkoxy, C1-C4-alkylthio and/or a phenyl radical; phenyl which is unsubstituted or substituted; R2 is hydrogen, hydroxyl, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio, or CR2 is linked to CR12 as indicated under Z to give a 5- or 6-membered ring; X is nitrogen or methine; Y is nitrogen or methine; Z is nitrogen or CR12, where R12 is hydrogen, halogen or C1-C4-alkyl, or CR12 forms together with CR2 or CR3 a 5- or 6-membered alkylene or alkenylene ring which can be unsubstituted or substituted and in which in each case one or more methylene groups can be replaced by oxygen, sulfur, â€”NH or â€”N(C1-C4-alkyl); wherein two of X, Y and Z denote nitrogen and the third denotes methine or CR12, respectively;R3 is hydrogen, hydroxyl, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio; or CR3 is linked to CR12 as indicated under Z to give a 5- or 6-membered ring; R4 and R5 are identical or different and denote: phenyl or naphthyl each of which is unsubstituted or substituted, or phenyl or naphthyl which are connected together in ortho positions by a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO2, NH or N-alkyl group, C3-C8-cycloalkyl which is unsubstituted or substituted; R6 is a group â€ƒwhere R13 and R14 are identical or different, and R13 is C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, wherein each of these radicals is substituted by one or more radicals selected from: carboxyl, amino, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C3-C8-alkylcarbonylalkyl, C3-C8-cycloalkyl, 1-indanyl, 2-indanyl, 1-tetrahydronaphthyl, 2-tetrahydronaphthyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, phenoxy and phenyl, the phenyl radicals in turn being unsubstituted or substituted by one or more radicals selected from: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, and C1-C4-alkylthio; C3-C8-cycloalkyl, which is unsubstituted or substituted by one or more radicals selected from: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkylthio and C1-C4-haloalkoxy; phenyl or naphthyl, each of which is unsubstituted or substituted by one or more radicals selected from: halogen, nitro, carbamoyl, mercapto, carboxyl, cyano, hydroxyl, amino, R15, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C3-C6-alkenyloxy, C1-C4-haloalkyl, C3-C6-alkynyloxy, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, methylenedioxy, ethylenedioxy and phenyl, where the phenyl ring is unsubstituted or substituted by one or more radicals selected from: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and C1-C4-alkylthio; R14 is one of the groups indicated for R13, or is C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, each of which is unsubstituted or substituted by one or more radicals selcted from: halogen, hydroxyl, mercapto, nitro, carbamoyl, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy, C3-C6-alkynyloxy, C1-C4-alkylthio and C1-C4-haloalkoxy; or R13 and R14 together form a C3-C7-alkylene chain which is closed to a ring and which is unsubstituted or substituted by one or more radicals selected from: C1-C4-alkyl, C1-C4-alkylthio, C1-C4-alkoxy, C1-C4-haloalkyl and C1-C4-haloalkoxy, and where one methylene group of the alkylene chain is optionally replaced by oxygen, sulfur, nitrogen or N(C1-C4-alkyl); or R13 and R14 together form a C3-C7-alkylene chain or C4-C7-alkenylene chain, which is closed to a ring, where each chain is unsubstituted or substituted by one to three C1-C4-alkyl radicals, and where each chain is fused to a phenyl ring which in turn is unsubstituted or substituted by one or more radicals selected from: halogen, C1-C4-alkyl, C1-C4-alkylthio, C1-C4-alkoxy, C1-C4-haloalkyl, C1-C4-haloalkoxy, hydroxyl, carboxyl and amino; R7 and R8 are identical or different and denote: hydrogen, C1-C4-alkyl; R15 is C1-C4-alkyl, C1-C4-alkylthio, C1-C4-alkoxy, each of which is unsubstituted or carries one of the following radicals: hydroxyl, carboxyl, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, carbamoyl and CON(C1-C4-alkyl)2; R18 is hydrogen; C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, phenyl, naphthyl, C3-C8-cycloalkyl, where these radicals are unsubstituted or substituted; R19 is C1-C8-alkylcarbonyl, C2-C8-alkenylcarbonyl, C2-C8-alkynylcarbonyl, benzyloxycarbonyl, C3-C8-cycloalkylcarbonyl, phenylcarbonyl or naphthylcarbonyl, where the abovementioned radicals are unsubstituted or substituted; C1-C8-alkylsulfonyl, C3-C8-alkenylsulfonyl or C3-C8-alkynylsulfonyl, phenylsulfonyl or naphthylsulfonyl, each of which is unsubstituted or substituted; C3-C8-cycloalkylsulfonyl; R20 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted; R21 is hydrogen, C1-C4-alkyl; W is sulfur or oxygen, or a physiologically tolerated salt or an enantiomerically pure or diastereomerically pure form.