Patent TW-I247741-B (TW)
Title: Substituted benzimidazoles, the preparation and use thereof
Inventor: LUBISCH WILFRIED
IPC: A61K31/4184
Filed: 1999-11-26
Granted: 2006-01-21
Abstract: Compounds of the formula Ia or Ib, where R1 is hydrogen or branched or straight-chain C1-C6-alkyl, where one carbon atom of the alkyl radical may furthermore carry ORS (where R5 is hydrogen or C1-C4-alkyl), or one carbon atom in the chain may also carry an =O group or a group NR8R9, where R8 and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the carbon chains in R8 or R9 or the ring formed by NR8R9 may furthermore carry a radical R6 which, independently of R2, may have the same meaning as R2, R4 is hydrogen, branched or straight-chain C1-C6-alkyl, chlorine, bromine, fluorine, nitro, cyano, NR8R9, NH-CO-R10 or OR8, where R8 and R9, independently of one another, are each hydrogen or C1-C4-alkyl and NR8R9 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical (branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R41 COOR41 or phenyl), and R10 may be hydrogen, C1-C4-alkyl or phenyl and R41 may have the same meanings as R21, A is a saturated or monounsaturated heterocyclic, 4- to 8-membered ring which contains one or two nitrogen atoms, it being possible for an oxygen or sulfur atom additionally to be incorporated, which oxygen or sulfur atom is substituted by R2 and R3, where R2 is hydrogen, branched or straight-chain C1-C8-alkyl which may furthermore be substituted by R23, and a carbon atom of the chain may carry an =O group, C3-C7-cycloalkyl-C1-C4-alkyl, -CO-(NH)0,1-R21, COOR21 or phenyl, where R21 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, phen-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl, and each radical may furthermore carry (CH2)0-2-R23, and the respective phenyl ring in turn may furthermore be substituted by 1, 2 or 3 of the following radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, -(CH2)0-2, NR24R25, NH-CO-R10, OR10, COOR10, SO2-C1-C4-a1kyl, SO2Ph, SO2NH, NHSO2-C1-C4-alkyl, NHSO2Ph and CF3, where R24 and R25, independently of one another, are each hydrogen or C1-C4-alkyl and NR24R25 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R22, COOR22 (where R22 is hydrogen, branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C3-C7-cycloalkyl or phenyl) or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and, R23 is NR26R27 where R26 and R27 are each hydrogen, C1-C6-alkyl, C0-C4-alkylphenyl, where the phenyl ring may furthermore be substituted by up to 3 radicals Cl, F, Br, I, C1-C4-alkyl, CF3, CN, SO2-C1-C4-alkyl, SO2-phenyl, NO2, NH2, NHCO-C1-C4-alkyl, NHCO-phenyl, OH, O-C1-C4-alkyl, O-C1-C4-alkylphenyl, and NR26R27 may also be a cyclic amine having 3 to 8 members, where a further hetero atom such as O, N and S may also additionally be present, and the ring may furthermore be substituted by a radical R28 where R28 may be C1-C4-alkyl and C1-C4-alkylphenyl, R3 is hydrogen, branched or straight-chain C1-C8-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl which is unsubstituted, or substituted by C1-C6-alkyl or C3-C7-cycloalkyl which is unsubstituted or substituted by C1-C6-alkyl, where one carbon atom of the radical may furthermore carry a phenyl ring which in turn may also be substituted by 1, 2 or 3 of the following. Radicals: chlorine, fluorine, bromine, iodine, branched and straight-chain C1-C4-alkyl, nitro, CF3, cyano, (CH2)0-2, NR32R33, NH-CO-R10, OR10, COOR10, SO2-C1-C4-alkyl, SO2Ph, CH3, SO2NH, NHSO2-C1-C4-alkyl, NHSO2Ph and CF3, where R32 and R33, independently of one another, are each hydrogen or C1-C4-alkyl and NR32R33 together may be a cyclic amine having 4 to 8 ring atoms, where the ring may furthermore carry a radical of branched or straight-chain C1-C6-alkyl, C3-C7-cycloalkyl-C1-C4-alkyl, CO-R31, COOR31 or phenyl, and R10 is hydrogen, C1-C4-alkyl or phenyl, and R31 may have the same meaning as R21, and their tautomeric forms, possible enantiomeric and diastereomeric forms, their prodrugs and possible physiologically tolerated salts.