SI9210098A - Benzimidazoles, drugs with this compounds, and process for their preparation - Google Patents

Abstract

1-Biphenylylmethyl-benzimidazole derivs. of formula (I) and their salts are new. (A) where: R1 = F, Cl, Br, 1-4C alkyl, cycloalkyl, CH2F, CHF2 or CF3 and is in the 4 position; R2 = R2 or may also be R2 when R4 = 1H-tetrazolyl; R'2 = 3-5C alkoxy substd. in the 3, 4 or 5 position by imidazolyl, or 2-5C alkoxy substd. in the 2, 3, 4 or 5 position by benzimidazolyl or tetrahydrobenzimidazolyl; R2 = e.g. (a) 2-(1-imadazolyl)ethoxy, 1-4C alkylsulphonyloxy, OSO2Ph or phenylalkylsulphonyloxy; (b) acylamino opt. N-substd. by 1-6C alkyl, Ph, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenylyl, where acyl is 1-7C alkanoyl, 2-4C alkoxycarbonyl, 1-6C alkylsulphonyl, benzoyl, phenylsulphonyl, phenylalkylsulphonyl, naphthylsulphonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl, where phenyl rings are opt. substd. by 1-2 of F, Cl, Br, Me and OMe, or 3-oxopyridazylinyl or (l) 3-oxodihydropyridazinyl, opt. 2-substd. by alkyl or phenylalkyl and opt. further C-substd. by 1-2 alkyl gps., Het = a C- or imino-bonded 5-membered heteroaromatic ring or a C-bonded 6-membered heteroaromatic ring. (B) where: R1 = H or F, Cl, Br, 1-4C alkyl, CH2F, CHF2 or CF3 in the 5, 6 or 7 position; R2 = Het or a gp. as defined in (l) above; R3 and R4 are as defined in (A); provided that: (a) R2 is not 3-methylimidazo (4,5-b)pyridin-2-yl or 3-n-hexylimidazo(4,5-b) pyridin-2-yl in the 6 position when R1 = H, R3 = n-Pr and R4 = COOH; (b) R2 is not benzoxazol-2-yl in the 5 or 6 position when R1 = H, R3 = n-Pr or n-Bu and R4 = 1H-tetrazolyl; (c) R2 is not 1-methyl-2-benzimidazolyl in the 5 or 6 position or 1-n-butyl-2-benzimidazolyl, 1,5-dimethyl-2-benzimidazolyl or 1-methyl-5-trifluoromethyl -2-benzimidazolyl in the 6 postion when R1 = H, R3 = n-Pr and R4 = COOH; (d) R2 is not 1-methyl-2-benzimidazolyl in the 6 position when R1 = H, R3 = n-Bu and R4 = COOH or 1H-tetrazolyl; (e) R2 is not 2-benzimidazolyl in the 6 position when R1 = H, R3 = n-Bu and R4 = COOH; unless otherwise stated, alkanoyl, alkyl and alkoxy gps. are 1-3C and cycloalkyl gps. are 3-7C.

Description

their 1-, 3-isomeric mixtures as well as their salts, in particular for the pharmaceutical use of their physiologically acceptable salts with inorganic or organic acids or bases, are even more valuable angiotensin antagonists, in particular angiotensin-II antagonists.

In the above general formula I mean

Rj in position 4 is a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms, a cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group, and

R _{2 is an} alkoxy group of 3 to 5 carbon atoms in position 3,4 or 5 substituted with an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted with a benzimidazolyl group, or tetrahydrobenzimidazolyl group or even if R ₄ represents a tet-tetrazolyl group, 2- (imidazol-1-yl) -ethoxy group, alkylsulfonyloxy group having 1 to 4 carbon atoms, benzenesulfonyloxy or phenylalkane sulfonyloxy group, optionally on a nitrogen atom with alkyl a group of 1 to 6 carbon atoms with a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group substituted acylamino group in which the acyl residue represents an alkanoyl group of 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group having from 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, preceded by m said phenyl nucleus may in each case be mono- or disubstituted by a fluorine, chlorine or bromine atom, methyl or methoxy group, and the substituents may be the same or different, phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, being a carbonyl group the phthalimino group substituted with a methylene, alkylmethylene or dialkylmethylene group, as well as the methylene group in the homophthalimino group may be substituted by one or two alkyl groups and the abovementioned phenyl cores are mono- or substituted by alkyl or alkoxy groups, the substituents being optionally substituted. identical or different and may be simultaneously fully or partially hydrated, optionally with one or two alkyl groups or with a tetramethylene or pentamethylene group substituted 5-, 6- or 7-membered alkyleneimine or alkenyleneimine group in which the methylene group may be substituted by carbonyl or a sulfonyl group, an imino group Bicycloalkane-2,3-dicarboxylic acids or imino bicycloalkene 2,3,3-dicarboxylic acids, in which the bicycloalkane and bicycloalkenes each contain 9 ah 10 carbon atoms, may be substituted by 1, 2 or 3 methyl groups and the endomethylene group may be substituted with an oxygen atom, optionally one or two alkyl groups each having 1 to 6 carbon atoms, a substituted amidine group, a glutamic acid imine group in which the n-propylene group is perfluorinated, which may be substituted by one or two alkyl groups, or with a tetramethylene or pentamethylene group, optionally an alkyl or phenyl group, a mono- or disubstituted imido group of maleic acid, the substituents being the same or different, a 5-membered heteroaromatic ring containing an imino group via a carbon atom or via an imino group , an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or via a carbon atom in a 6-membered heteroaromatic ring containing 1 or 2 nitrogen atoms, wherein said heteroaromatic rings in the carbon framework may be substituted by an alkyl group of 1 to 6 carbon atoms or a phenylalkyl group and bonded to the 6-membered heteroaromatic rings each time through two adjacent carbon atoms of an n-propylene or n-butylene group or bonded to both 5-membered and 6-membered heteroaromatic rings each time via two adjacent carbon atoms, a 1,3-butadienyl group or via an imino group and a neighboring carbon atom n-butylene or 1,3-butadienyl groups and in the thus formed annelated pyridine ring may be substituted by a methine group with a nitrogen atom and a vinylene group in position 3, 4 to the nitrogen atom of the resulting pyridine ring, with a sulfur atom or in the thus formed annelated phenyl ring one or two methine groups may be replaced by nitrogen atoms, with the additional previously mentioned condensed a romatic ah heteroaromatic rings in the carbon framework may be monosubstituted by a fluorine atom, chlorine ah bromine, alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, aminocarbonyl, aminocarbonyl, aminocarbonyl difluoromethyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group ah disubstituted by a fluorine or chlorine atom, by methyl, methoxy or hydroxy groups, such as two methyl substituents in position 1,2 in relation to each other or may be linked to methylene by a bridge or methylene optionally, and optionally in the imidazole ring, the NH group present may be substituted with an alkyl group of 1 to 6 carbon atoms, a phenylalkyl group or a cycoloalkyl group, or a pyrrolidine, piperidine or pyridine ring attached to the carbon atom, to which the pyridine ring is attached through two adjacent carbon atoms it condenses n is a phenyl radical and is a methylene group which is adjacent to the nitrogen atom in the pyrrolidine or piperidine ring with a carbonyl group, optionally an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group substituted imidazolidinedione dihydro-pyridine-a-pyridine a pyridazin-3-one group which may be substituted in the 2-position with a, optionally substituted phenyl group, an alkyl group, and additionally in a carbon framework with 1 or 2 alkyl groups,

Is a group in which they are represented

R _{5 is} a hydrogen atom, an alkyl group of 1 to 8 carbon atoms, a cycloalkyl group of 5 to 7 carbon atoms or a phenylalkyl group,

R _{6 is} a hydrogen atom, an alkyl group of 1 to 8 carbon atoms, an alkenyl group of 3 to 5 carbon atoms, a phenyl group, a phenylalkyl group or a cycloalkyl group of 5 to 7 carbon atoms,

R _? a hydrogen atom or an alkyl group of 1 to 6 carbon atoms or one of the residues R ₅ , R ₆ or R _? also a bicyclohexyl or biphenylyl group or

R ₆ and R _? together with a nitrogen atom lying between them an alkyleneimine group of 4 to 6 straight carbon atoms or a morpholine group, or

R ₅ and R ₆ together are an alkylene group of 2 to 4 carbon atoms, a 1H, 3H-quinazolin-2,4-dione-3-yl- or pentamethylene-oxazolin-2-yl group, or

R 1 is a hydrogen atom or in the 5, 6 or 7 position of a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms, a fluoromethyl, difluoromethyl or trifluoromethyl group, and

R 5 is a 5-membered heteroaromatic ring containing a imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or a 6-membered heteroaromatic ring containing 1 through a carbon atom or 2 nitrogen atoms, the aforementioned heteroaromatic rings being optionally substituted in the carbon framework by an alkyl group of 1 to 6 carbon atoms or a phenylalkyl group and bonded to the 6-membered heteroaromatic rings each via two adjacent carbon atoms by n-propylene or n-butylene groups or bonded to both 5-membered and 6-membered heteroaromatic rings each via two adjacent carbon atoms of the 1,3-butadienyl group or via imino group and adjacent carbon atom of the n-butylene or 1,3-butadienyl group and in the thus formed annelated pyridine ring the methine group is replaced by the nitrogen atom and the vinylene group in position 3, 4 to the nitrogen atom of the resulting p of the iridine ring, with a sulfur atom or in the thus formed annelated phenyl ring, one or two methine groups are replaced by nitrogen atoms, wherein the aforementioned condensed aromatic or heteroaromatic rings in the carbon framework may be monosubstituted by a fluorine, chlorine or bromine atom alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, fluoromethyl, difluoromethyl, trifluoro-methylsulfonylamino, sulfonosulfonyl, alkanoylsulfonylsulfonyl, alkanoyl with a fluorine or chlorine atom, with methyl, methoxy or hydroxy groups, as well as two methyl substituents in position 1,2 may be connected to each other by a methylene or ethylene bridge, and optionally an NH group may be present in the imidazole ring substituted with an alkyl group of 1 to 6 carbon atoms ia, with a phenylalkyl group or a cycloalkyl group, where, when (i) R 1 represents a hydrogen atom, R _{3 is a} n-propyl group and R _{4 is a} carboxy group, R ₂ in position 6 cannot represent 3-methyl imidase [4, 5-b] pyridin-2-yl or 3-hexyl-imidazo [4,5-b] pyridin-2-yl groups or if (ii) R 1 is a hydrogen atom, R _{3 is a} n-propyl or n-butyl group, and R _{4 is a} 1H-tetrazolyl group, R2 in position 5 or 6 cannot represent a benzoxazol-2-yl group or, if (iii) R1 is a hydrogen atom, R _{3 is a} n-propyl group and R _{4 is a} carboxy group, R _{2 is} in position 5 or 6 cannot represent the 1-methylbenzimidazol-2-yl group, or in position 6 it cannot represent the 1-butylbenzimidazol-2-yl, 1,5-dimethylbenzimidazol-2yl or 1-methyl-5-trifluoromethyl-benzimidazol-2-yl group, or if (iv) R _{1 is} a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is a} carboxy or 1H-tetrazolyl group, 1 'in position 6 cannot represent a 1-methylbenzimidazol-2-yl group, or if (v) Rj a hydrogen atom, R _{The 3} n-butyl group and the R ₄ carboxy group, R ₂ in position 6 cannot represent the benzimidazol-2-yl group, or a pyrrolidine, piperidine or pyridine ring bonded through the carbon atom, condensing to the pyridine ring via two adjacent carbon atoms a phenyl residue and the methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring may be replaced by a carbonyl group,

R _{3 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms in which the methylene group may be replaced by an oxygen or sulfur atom or a cycloalkyl group of 3 to 5 carbon atoms, and

R ₄ carboxy, cyano, lH-tetrazolyl or 1-trifenilmetiltetrazolilno group, an alkoxy carbonyl group with a total of 2 to 5 carbon atoms, alkansulfonilaminokarbonilno, arilsul6 fonilaminokarbonilno or trifluormetansulfonilaminokarbonilno group, while, unless otherwise stated previously mentioned alkanoyl, alkyl or alkoxy the moiety may each contain 1 to 3 carbon atoms as well as the aforementioned cycloalkyl moiety may each contain 3 to 7 carbon atoms.

For residues having the meanings given initially in the definition for residues R _x to R _3, it is appropriate to mean, for example:

R _x : hydrogen, fluorine, chlorine or bromine atom, methyl, ethyl, n-propyl, isopropyl, isobutyl, n-butyl, 1-methyl-n-propyl, 2-methyl-n-propyl, tert-butyl, cyclopropyl, a cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, fluoromethyl, difluoromethyl or trifluoromethyl group,

R ₂ : 3- (imidazol-1-yl) -propoxy, 4- (imidazol-1-yl) -butoxy, 5- (imidazol-1-yl) -pentoxy,

2-benzimidazol-1-yl) -ethoxy, 3- (benzimidazol-1-yl) -propoxy, 4- (benzimidazol-1-yl) butoxy, 5- (benzimidazol-1-yl) -pentoxy, 2- (tetrahydro) -benzimidazol-1-yl) -ethoxy,

3- (tetrahydrobenzimidazol-1-yl) -propoxy, 4- (tetrahydrobenzimidazol-1-yl) -butoxy, 5- (tetrahydrobenzimidazol-1-yl) -pentoxy, methanesulfonyloxy, ethanesulfonyloxy, n-propanesulfonyloxy, isopropanesulfonyloxy, isopropanesulfonyloxy, isopropanesulfonyloxy benzenesulfonyloxy,

4- fluorobenzenesulfonyloxy, 4-bromobenzenesulfonyloxy, 4-methylbenzenesulfonyloxy,

4-methoxybenzenesulfonyloxy, 3,4-dichlorobenzenesulfonyloxy, phenylmethanesulfonyloxy,

2-feniletansulfoniloksi, 3-fenilpropansulfoniloksi, formylamino, acetylamino, propionylamino, butanoilamino, izobutanoilamino, pentanoylamino, 3-metilbutanoilamino, heksanoilamino, methoxycarbonylamino, ethoxycarbonylamino, n-propoksikarbonilamino, izopropoksikarbonilamino, methanesulfonylamino, ethanesulfonylamino, n-propansulfonilamino, Isopropanesulfonylamino, n-butansulfonilamino, n-pentansulfonylamino, benzamido, benzenesulfonylamido, 4-fluorobenzenesulfonamido, 4-bromobenzenesulfonamido, 4-methylbenzenesulfonamide, phenolamide naphthalen-2-yl-sulfonylamido, cyclopentylcarbonylamido, cyclohexylcarbonylamido, cycloheptylcarbonylamido, phenylacetylamido, 3-phenylpropionylamido, cyclopentylacetylamido, 3-cyclopentylpropionylamido, cyclohexylacetylamido, cyclohexylacetylamido, 3-cyclohexylacetylamido, 3-cyclohexylacetylamido, 3-cyclohexylacetylamido, 3-cyclohexylacetylamido, 3-cyclohexylacetylamidoethyl to, N-methyl7 formylamino, N-methyl-acetylamino, N-methyl-propionylamino, N-methyl-butanoylamino, N-methyl-isobutanoylamino, N-methyl-pentanoylamino, N-methyl-3-methyl-butanoylamino, N-methyl -hexanoylamino, N-methyl-methoxycarbonylamino, N-methyl-ethoxycarbonylamino, N-methyl-n-propoxycarbonylamino, N-methyl-isopropoxycarbonylamino, N-methyl-methanesulfonylamino, N-methyl-ethanesulfonylamino, N-methylsulfonylamino, N-methylsulfonylamino, N-methylsulfonylamino -methyl-isopropanesulfonylamino, N-methyl-n-butanesulfonylamino, N-methyl-pentanesulfonylamino, N-methyl-n-hexansulfonylamino, N-methyl-benzamido, N-methylbenzenesulfonylamido, N-methyl-4-fluorobenzenesulfonamido, 4 -chlorobenzenesulfonamido, N-methyl-4-bromobenzenesulfonamido, N-methyl-4-methylbenzenesulfonamido, N-methyl-4-methoxybenzenesulfonamido, N-methyl-phenylmethanesulfonylamido, N-methyl-2-phenylethanesulfonylamido, N-methyl-phenylamino, N-methyl-3-phenylamino -methylnaphthalen-1-yl-sulfonamido, N-methyl-naphthalen-2-yl-sulfonylamido, N-methyl-cyclopentylcarbonylamido, N-methyl-cyclohexylcarbonylamido, N-methyl -cycloheptylcarbonylamido, N-methyl-phenylacetamido, N-methyl-3-phenylpropionylamido, N-methyl-cyclopentylacetylamido, N-methyl-3-cyclopentylpropionylamido, N-methyl-cyclohexylacetylamido, N-methyl-3-cycloylhexyl-ethylpropylamino, , N-methyl-3cyclo-heptylpropionylamido, N-ethyl-formylamino, N-ethyl-acetylamino, N-ethyl-propionylamino, N-ethyl-butanoylamino, N-ethyl-isobutanoylamino, N-ethylpentanoylamino, N-ethyl-3-methyl-butanoylamino , N-ethyl-hexanoylamino, N-ethylmethoxycarbonylamino, N-ethyl-ethoxycarbonylamino, N-ethyl-n-propoxycarbonylamino, N-ethyl-isopropoxycarbonyl-amino, N-ethyl-methanesulfonylamino, N-ethylethanesulfonylamino, N-ethylethanesulfonylamino, N-ethylethanesulfonylamino - amino, N-ethyl-isopropanesulfonylamino, N-ethyl-n-butansulfonylamino, N-ethyl-n-pentanesulfonylamino, N-ethyl-hexansulfonylamino, N-ethyl-benzamido, N-ethyl-benzenesulfonylamido, N-ethyl-4fluorobenzenesulfonyl -ethyl-4-chlorobenzenesulfonamido, N-ethyl-4bromobenzenesulfonamido, N-ethyl-4-methylbenzenesulfonamido, N-ethyl-4-methoxybenzenes lfonamido, N-ethyl-phenylmethanesulfonylamido, N-ethyl-2-phenylethanesulfonylamido, N-ethyl-3-phenylpropanesulfonylamido, N-ethyl-naphthalen-1-yl-sulfonamido, N-ethyl-naphthalen2-yl-sulfonylamido, N- ethyl-cyclopentylcarbonylamido, N-ethylcyclohexylcarbonylamido, N-ethyl-cycloheptylcarbonyl amido, N-ethyl-phenylacetylamido, N-ethyl3-phenylpropionylamido, N-ethyl-cyclopentylacetylamido, N-ethyl-3-cyclopentylamino, N-ethyl-3-yl-cyclopentylamino -ethyl-3-cyclohexylpropionylamido, N-ethyl-cycloheptylacetylamido, N-ethyl-3-cycloheptylpropionylamido, Nn-propyl-formylamino, Nn-propyl-acetylamino, Nn-propyl-propionylamino, Nn-propyl-butanoylamino, N-propyl-butanoylamino, N , Nn-propyl-pentanoylamino, Nn-propyl- (3-methylbutanoyl) 8 amino, Nn-propyl-hexanoylamino, N-isopropyl-formylamino, N-isopropyl-acetylamino, N-isopropyl-propionylamino, N-isopropyl-butanoylamino, N -isopropyl-isobutanoylamino, N-isopropyl-pentanoylamino, N-isopropyl- (3-methylbutanoyl) amino, N-isopropyl-hexanoylamino, Nn-butyl-form ylamino, Nn-butyl-acetylamino, N-n-butyl-propionylamino, Nn-butyl-butanoylamino, Nn-butyl-isobutanoylamino, N-n-butyl-pentanoylamino, Nn-butyl- (3-methyl-butanoyl) amino, Nn-butyl-hexanoylamino , N-isobutyl-formylamino, N-isobutyl-acetylamino, N-isobutyl-propionylamino, N-isobutyl-butanoylamino, N-isobutyl-isobutanoylamino, N-isobutyl-pentanoylamino, N-pentyl-formylamino, Nn-pentyl-acetylamino, Nn-pentyl-acetylamino -pentyl-propionylamino, Nn-pentylbutanoylamino, Nn-pentyl-isobutanoylamino, Nn-pentyl-pentanoylamino, N- (1-methylbutyl) -formylamino, N- (1-methyl-butyl) -acetylamino, N- (1-methyl- butyl) -propionylamino, N- (1-methyl-butyl) -butanoylamino, N- (1-methyl-butyl) -isobutanoylamino, N- (1-methylbutyl) -pentanoylamino, N- (2-methyl-butyl) -formylamino , N- (2-methyl-butyl) -acetylamino, N- (2-methyl-butyl) -propionylamino, N- (2-methyl-butyl) -butanoylamino, N- (2-methyl-butyl) isobutanoylamino, N- (2-methyl-butyl) -pentanoylamino, N- (3-methyl-butyl) -formylamino, N- (3-methyl-butyl) -acetylamino, N- (3-methyl-butyl) -propionylamino, N - (3-methyl-butyl) butanoylamino, N- (3-methyl-butyl) -isobutanoylamino, N- (3-methyl-butyl) -pentanoylamino, Nn-hexyl-formylamino, Nn-hexyl-acetylamino, Nn-hexyl- propionylamino propionylamino propionylamino propionylamino propylamino -isopropyl-3- (cyclohexyl) propionylamino, Nn-butyl-cyclohexylcarbonylamino, Nn-butyl-cyclohexylacetylamino, Nn-butyl-3- (cyclohexyl) propionylamino, N-isobutyl-cyclohexylcarbonylamino, N-isobutyl-cyclobutyl-butyl-ethylbutylamino-ethyl) 3- (cyclohexyl) propionylamino, Nn-pentyl-cyclohexylcarbonylamino, Nn-pentyl-cyclohexylacetylamino, Nn-pentyl-3- (cyclohexyl) propionylamino, Nn-hexylcyclohexylcarbonylamino, Nn-hexyl-cyclohexyl-cyclohexyl-cyclohexyl-cyclohexyl-cyclohexyl-cyclohexyl-cyclohexyl-cyclohexyl) , 5-methoxy-phthalimino, 5,6-dimethoxy-phthalimino, 6-metho xy-phthalimino, homophthalimino, 4,4-dimethyl-homophthalimino, 7-methoxyhomophthalimino, 6,7-dimethoxy-homophthalimino, 7-methoxy-4,4-dimethyl-homophthalimino, 6,7-dimethoxy-4,4-dimethyl- homophthalimino, 1,2,3,6-tetrahydrophthalimino, hexahydrophthalimino, cis-hexahydrophthalimino, trans-hexahydrophthalimino, 1-oxo-isoindolin-2-yl, 3,4-dimethyl-phthalimino, 4,5-dimethyl-1,2,3, 6-tetrahydrophthalimino, 4,5-dimethyl-hexahydrophthalimino, 4,5-dimethyl-1-oxo-isoindolin-2-yl, 3,4-dimethoxy-phthalimino, 4,5-dimethoxy-1,2,3,6-tetrahydrophthalimino, 4,5-dimethoxy-hexahydrophthalimino, 4,59 dimethoxy-1-oxo-isoindolin-2-yl, 2-carboxyphenylmethylamino, 2-carboxyphenylmethylene-carbonylamino, pyrrolidino, 2-methylpyrrolidino, 3-ethylpyrrolidino,

3- isopropylpyrrolidino, piperidino, 3-methylpiperidino, 4-methylpiperidino, 4-ethylpiperidino, 4-isopropylpiperidino, hexamethylenimino, 3-methylhexamethylenimino,

4- methylhexamethylenimino, 3-ethylhexamethylenimino, 4-isopropylhexamethylenimino,

3.3-dimethyl-pyrrolidino, 3,4-dimethyl-pyrrolidino, 3,3-dimethyl-piperidino, 3,4-dimethylpiperidino, 4,4-dimethyl-piperidino, 3,3-dimethyl-hexamethylenimino, 3,4-dimethylhexamethylenimino, 4,4-dimethyl-hexamethylenimino, 3,5-dimethyl-hexamethylenimino,

3.3-tetramethylene-pyrrolidino, 3,3-pentamethylene-pyrrolidino, 3,3-tetramethylene-piperidino, 3,3-pentamethylene-piperidino, 4,4-tetramethylene-piperidino, 4,4pentamethylene-piperidino, 3,3-tetramethylene- hexamethylenimino, 3,3-pentamethylenehexamethylenimino, 4,4-tetramethylenehexamethylenimino, 4,4-pentamethylenehexamethylenimino, 2-oxo-pyrrolidino, 2-oxo-piperidino, 2-oxo-hexamethylenimino, propansultam-1-yl, butansultam, butansultam pentansultam-1-yl group, imino group, endo-bicyclo [2.2.2] oct-5-ene-2,3-dicarboxylic acid, imino group methyl-5-norbomen-2,3-dicarboxylic acid, 3,6- eridoxo-1,2,3,6-tetrahydrophthalimino group, imino group 5-norbornene-endo-2,3-dicarboxylic acid, glutarimino,

3.3-tetramethylene-glutarimino, 3,3-pentamethylene-glutarimino, 2,2-dimethyl-glutarimino, 3-methyl-glutarimino, 3,3-dimethyl-glutarimino, 3-ethyl-glutarimino, 3-ethyl-3-methylglutarimino, 1,3-cyclopentadicarbonyl-imino, 2,4-dimethyl-glutarimino, 2,4-di-propyl-glutarimino, glutaramino, 3,3-tetra-methylene-glutaramino, 3,3-pentamethylene-glutaramino, 2,2-dimethyl- glutaramino, 3-methyl-glutaramino, 3,3-dimethyl-glutaramino, 3-ethyl-glutaramino, 3-ethyl-3-methyl-glutaramino, 1,3-cyclopentadicarbonylamino, 2,4-dimethyl-glutaramino, 2,4-di- n-propyl-glutaramino, maleinamido, maleinimido,

2-methyl-maleinamido, 3-methyl-maleinamido, 2-methyl-maleinimido, 2-phenylmaleinamido, 3-phenyl-maleinamido, 2-phenyl-maleinimido, 2,3-dimethyl-maleinamido,

3-methyl-2-phenyl-maleinamido, 2-methyl-3-phenyl-maleinamido, 2-methyl-3-phenylmaleinimido, 2,3-diphenyl-maleinamido, 2,3-diphenyl-maleinamido, pyrrolidin-2-yl, pyrrolidin-2-one-5-yl, piperidin-2-yl, piperidin-2-one-1-yl, piperidin-2-one-6-yl, quinolin-2-yl, isoquinolin-1-yl, isoquinoline- 3-yl, pyridin-2-yl, 4-methylimidazol-2-yl, 1-methylimidazol-4-yl, 1-methylimidazol-5-yl, 1-hexyl-imidazol-4-yl, 1-hexylimidazol-5-yl, 1-benzylimidazol-4-yl, 1-benzylimidazol-5-yl, 1,2-dimethylimidazol-4-yl, 1,2-dimethylimidazol-5-yl, 11-pentyl-2-methyl-imidazol-4-yl, pentyl-2-methyl-imidazol-5-yl, 1-butyl-2-methyl-imidazol-4-yl, 1-butyl-2methyl-imidazol-5-yl, 1-benzyl-2-methyl-imidazol-4- Ilno, 1-benzyl-2-methyl-imidazol-510 ylno, benzimidazol-2-ylno, 1-methylbenzimidazol-2-ylio, 1-ethylbenzimidazol-2-ylio, l-propylbenzimidazol-2-yl, 1-isopropylbenzimidazol-2-yl -ylno, 1-butylbenzimidazol-2-yl, 1-isobutylbenzimidazol-2-yl, ln-pentylbenzimidazol-2yl, ln-hexylbenzyme idazol-2-yl, 1-cyclopropylbenzimidazol-2-yl, 1-cyclobutylbenzimidazol-2-yl, 1-cyclopentylbenzimidazol-2-yl, 1-cyclohexylbenzimidazol-2-yl, 5-nitrobenzimidazol-2-benzimide, 5-amino-5-amino-5-amino 2-yl, 5-acetamidobenzimidazol-2-yl, 5-methyl-benzimidazol-2-yl, 5-methoxy-benzimidazol-2-yl,

5-Ethoxy-benzimidazol-2-yl, 1-methyl-5-methoxy-benzimidazol-2-yl, 1,5-dimethylbenzimidazol-2-yl, 1,6-dimethyl-benzimidazol-2-yl, 1-4 dimethyl-benzimidazol-2-yl, 5,6-dimethyl-benzimidazol-2-yl, 1,5,6-trimethyl-benzimidazol-2-yl, 5-chlorobenzimidazol-2-yl, 5-chloro-1-methyl-benzimidazole- 2-yl, 6-chloro-1-methyl-benzimidazol-2-yl, 5,6-dichloro-1-methyl-benzimidazol-2-yl, 5-dimethylaminobenzimidazol-2-yl, 5-dimethylamino-1-ethyl- benzimidazol-2-yl, 5,6-dimethoxy-1-methyl-benzimidazol-2-yl, 5,6-drinethoxy-1-ethyl-benzimidazol-2-yl, 5-fluoro-1-methylbenzimidazol-2-yl, 6- fluoro-1-methyl-benzimidazol-2-yl, 5-trifluoromethylbenzimidazol-2-yl, 5-trifluoromethyl-1-methyl-benzimidazol-2-yl, 4-cyano-1-methylbenzimidazol-2-yl, 5-carboxy-1- methyl-benzimidazol-2-yl, 5-aminocarbonylbenzimidazol-2-yl, 5-aminocarbonyl-1-methyl-benzimidazol-2-yl, 5-dimethyl-aminosulfonyl-1-methyl-benzimidazol-2-yl, 5-methoxycarbonyl- 1-methyl-benzimidazol-2-yl,

5-methylaminocarbonyl-1-methyl-benzimidazol-2-yl, 5-dimethylaminocarbonyl-1-methylbenzimidazol-2-yl, 4,6-difluoro-1-methyl-benzimidazol-2-yl, 5-acetyl-1-methylbenzimidazole- 2-yl, 5,6-dihydroxy-1-methyl-benzimidazol-2-yl, imidazo [1,2a] pyridin-2-yl, 5-methyl-imidazo [1,2-a] pyridin-2-yl, 6-methyl-imidazo [1,2a] pyridin-2-yl, 7-methyl-imidazo [1,2-a] pyridin-2-yl, 8-methyl-imidazo [1,2a] pyridin-2-yl, 5,7-dimethyl-imidazo [1,2-a] pyridin-2-yl, 6-amino-carbonylimidazo [1,2-a] pyridin-2-yl, 6-chloro-imidazo [1,2-a] pyridin-2-yl, 6-bromimidazo [1,2-a] pyridin-2-yl, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyrimidin-2-yl, imidazo [1, 2-a] pyrimidin-2-yl, 5,7-dimethyl-imidazo [1,2-a] pyridin-2-yl, imidazo [4,5-b] pyridin-2-yl, 1-methyl-imidazo- [4,5-b] pyridin-2-yl, 1-n-hexyl-imidazo [4,5-b] pyridin-2-yl, 1-cyclopropyl-imidazo [4,5-b] pyridin-2-yl , 1-cyclohexylimidazo [4,5-b] pyridin-2-yl, 4-methyl-imidazo [4,5-b] pyridin-2-yl, 6-methylimidazo [4,5-b] pyridin-2- ilno, 1,4-dimethyl-imidazo [4,5-b] pyridin-2-yl o, 1,6-dimethylimidazo [4,5-b] pyridin-2-ylno, imidazo [4,5-c] pyridin-2-yl, 1-methyl-imidazo [4,5-c] pyridin-2- Ilno, 1-hexyl-imidazo [4,5-c] pyridin-2-yl, 1-cyclopropylimidazo [4,5-c] pyridin-2-yl, 1-cyclohexyl-imidazo [4,5-c] pyridine 2-yl, imidazo [2, 1b] thiazol-6-yl, 3-methyl-imidazo [2, 1b] thiazol-6-yl, 2-phenyl-imidazo [2, 1b] thiazol-6-yl, 3- phenyl-imidazo [2, 1b] thiazol-6-yl, 2,3-dimethyl-imidazo [2, 1b] thiazol-6-yl, 2,3-trimethylene-imidazo [2, 1b] thiazol-6-yl , 2,3-tetramethyleneimidazo [2, 1b] thiazol-6-yl, imidazo [1,2-c-] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1 , 2-b] pyridazin-2-yl, imidazo [4,5-c] pyridin-2-yl, purin8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] ] pyridazin-2-yl, imidazo [4,5-d] -pyridazin-2-yl, imidazolidin-2,4-dione-3-yl, 5-methyl-imidazolidin-2,4-dione-3-yl, 5- ethyl-imidazolidin-2,4-dione-3-yl, 5-n-propyl-imidazolidine-2,4-dione-3-yl, 5-benzyl-imidazolidine-2,4-dione-3-yl, 5- (2 -Phenylethyl) -imidazolidin-2,4-dione-3-yl, 5- (3-phenyl-propyl) -imide zolidin-2,4-dione-3-yl, 5,5-tetramethylene-imidazolidine-2,4-dione-3yl, 5,5-pentamethylene-imidazolidine-2,4-dione-3-yl, 5,5- Hexamethylene-imidazolidine 2,4-dione-3-yl, 1-methyl-imidazolidine-2,4-dione-3-yl, 1-benzyl-imidazolidine-2,4-dione-3-yl, 4,5-dihydro-2H- pyridazin-3-one-6-yl, 2-methyl-4,5-dihydro-2H-pyridazin-3-one-6yl, 2-ethyl-4,5-dihydro-2H-pyridazin-3-one-6- Ilno, 2-n-propyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 2-isopropyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 2-benzyl- 4,5-dihydro2H-pyridazin-3-one-6-yl, 2- (2-phenylethyl) -4,5-dihydro-2H-pyridazin-3-one-6-yl, 2- (3-phenylpropyl) -4 , 5-dihydro-2H-pyridazin-3-one-6-yl, 4-methyl-4,5-dihydro-2H-pyridazin-3on-6-yl, 5-methyl-4,5-dihydro-2H-pyridazine -3-one-6-yl, 4,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 5,5-dimethyl-4,5-dihydro-2H-pyridazin-3-one -6-yl, 4,5-dimethyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 2,4-dimethyl-4,5-dihydro-2H-pyridazin-3-one-6yl, 2 , 5-dimethyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 2,4,5-trimethyl-4,5-dihydro-2Hpyridaz in-3-one-6-yl, 2,4,4-trimethyl-4,5-dihydro-2H-pyridazin-3-one-6-yl, 2,5,5 trimethyl-4,5-dihydro-2H- 3-One-6-yl, 2H-pyridazin-3-one-6-yl, 2-methyl-pyridazin-3-one-6-yl, 2-ethyl-pyridazin-3-one-6-yl, 2- n-propyl-pyridazin-3-one-6-yl,

2-Isopropyl-pyridazin-3-one-6-yl, 2-benzyl-pyridazin-3-one-6-yl, 2- (2-phenylethyl) pyridazin-3-one-6-yl, 2- (3- phenylpropyl) 'pyridazin-3-one-6-yl, 4-methyl-pyridazin-3-one-6-yl, 5-methyl-pyridazin * 3-one-6-yl, 4,5-dimethyl-pyridazin-3-one -6-yl, 2,4-dimethylpyridazin-3-one-6-yl, 2,5-dimethyl-pyridazin-3-one-6-yl, 2,4,5-trimethyl-pyridazin-3-one-6-yl aminocarbonyl aminobenzoic acid , N-methylaminocarbonyl-n-pentylamino, N-methylaminocarbonyl-n-hexylamino, N-methylaminocarbonyl-n-octylamino, N-methylaminocarbonyl-cyclohexylamino, ethylaminocarbonylamino, N-ethylaminocarbonyl-methylamino, N-methylamino, N-ethylamino, N-ethylamino, N-methylamino n-hexylamino, N-ethylaminocarbonyl-n-heptylamino, N-ethylaminocarbonyl-cyclohexylamino, diethylaminocarbonyl mino, N- (diethylaminocarbonyl) -methylamino, N- (diethylaminocarbonyl) -ethylamino, N- (diethylaminocarbonyl) n-butylamino, N- (diethylaminocarbonyl) -n-hexylamino, N- (diethylaminocarbonyl) -noctylamino, isopropylamino-isopropylamino-isopropylamino-isopropylamino-isopropylamino; -methylamino, n-butylaminocarbonylamino, N- (n-butylaminocarbonyl) -methylamino, N- (n-butylaminocarbonyl) -ethylamino, N- (n-butylaminocarbonyl) -isopropylamino, N- (n-butylaminocarbonyl) -n-butylamino, N-butylamino - (n-butylaminocarbonyl) -n-hexylamino, N- (n-butylaminocarbonyl) -cyclohexylamino, N- (di- (n-butyl) -aminocarbonyl) -amino, N- (di- (n-butyl) -aminocarbonyl) -methylamino, N- (di- (n-butyl) -aminocarbonyl) -ethylamino, N- (di- (n-butyl) -aminocarbonyl) -n-butylamino, N- (di- (n-butyl) -aminocarbonyl) -Nhexylamino, N- (n-pentylaminocarbonyl) -methylamino, N- (n-pentylaminocarbonyl) ethyl-amino, N- (n-hexylaminocarbonyl) -ethyl-amino, n-hexylaminocarbonylamino, n-heptylaminocarbonylamino, n-octylaminocarbonylamino, n-octylaminocarbonylamino, n-octylaminocarbonylamino (n-hexylaminocarbonyl) -n-butylamino, N- (n-hexylaminocarbonyl) -n-pentyl lamino, N- (n-hexylaminocarbonyl) -n-hexylamino, N- (n-hexylaminocarbonyl) -cyclohexylamino, di (n-hexyl) -aminocarbonylamino, N- (di- (n-hexyl) -aminocarbonyl) -methylamino, N Aminoxylate (IoT) hexylamino-carboxylic acid-free aminocarbonylamino, pyrrolidinocarbonylamino, pyrrolidinocarbonylmethylamino, piperidinocarbonylamino, hexamethyleneiminocarbonylamino, morpholinocarbonylamino, 3,4,5,6tetrahydro-2-pyrimidon-1-yl, 3-methyl-3,4,5-tetrahydro-3-pyrimidine no,

3-ethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-n-propyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-isopropyl-3, 4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-n-butyl 3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-isobutyl-3,4,5,6- tetrahydro-2-pyrimidon-lyl, 3-n-pentyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-n-hexyl-3,4,5,6-tetrahydro-2- pyrimidon-1-yl, 3-cyclopentyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-cyclohexyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-cycloheptyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-benzyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3,4,5,6- tetra13 hydro-2 (1H) -pyrimidon-1-yl, 3-methyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidon-1-yl, 3-ethn-3,4,5,6 -tetrahydro-2 (1H) -pyrimidon-1-yl, 3-n-propyl-3,4,5,6-tetrahydro2 (1H) -pyrimidon-1-yl, 3-isopropyl-3,4,5,6 -tetrahydro-2 (1H) -pyrimidon-1-yl, 3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidon-1-yl, 3- (2-phenylethyl) -3,4 , 5,6-tetrahydro-2 (1H) -pyrimidon-1-yl or 3- (3-phenylpropyl) -3,4,5,6-tetrahydro-2 (1H) pyrimidon-1-yl group, and

R ₃ : hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl tert-butyl, n-pentyl, 1-methyl-butyl, 2-methyl-butyl, 3-methyl-butyl, cyclopropyl, cyclobutyl , cyclopentyl, methoxy, ethoxy, n-propoxy, isobutoxy, n-butoxy, methyl mercapto, ethyl mercapto, n-propyl mercapto, isopropyl mercapto or n-butyl mercapto group.

Preferred compounds of the above general formula I are those in which they are understood

Rj in position 4 is a fluorine, chlorine or bromine atom, an alkyl group of 1 to 3 carbon atoms, a cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group, and

R _{2 is an} alkoxy group of 3 to 5 carbon atoms in position 3,4 or 5 substituted by an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted by benzimidazolyl or tetrahydrobenzimidazolyl optionally substituted on the nitrogen atom with an alkyl group of 1 to 5 carbon atoms, an acylamino group in which the acyl residue represents an alkanoyl group with 2 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group with 1 to 3 the carbon atoms or the benzenesulfonyl group, the phthalimino or homophthalimino group, wherein the carbonyl group in the phthalimino group is replaced by a methylene group as well as the methylene group in the homophthalimino group may be substituted by one or two alkyl groups, optionally one or two alkyl groups, or with a tetramethylene or pentamethylene group substituted 5-, 6- or 7-membered alkylimino or alkenyleneimino group in which methylene a group may be substituted by a carbonyl or sulfonyl group, a glutaric acid imine group in which the n-propylene group is perfluorinated, which may be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, optionally a mono-alkyl or phenyl group - or a disubstituted maleic acid imido group, wherein the substituents may be the same or different, optionally with one or two alkyl groups each having 1 to 4 carbon atoms, a substituted amidine group, optionally in position 1 with an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, the phenyl nucleus of one of the aforementioned benzimidazole groups may be further substituted by a fluorine atom, methyl or trifluoromethyl group, imidase [2, 1b] thiazol-6-yl , imidazo [1,2-a] pyridin-2-yl, 5,6,7,8-tetrahydroimidazo [1,2-a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-2- ilno, imidazo [4,5-b] pyridine -2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1 , 2-b] pyridazin-2-yl, imidazo [4,5-c] pyridin-2-yl, purin-8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5 -c] pyridazin-2-yl, or an imidazo [4,5-d] pyridazin-2-yl group, bonded via a carbon atom to a pyrrolidine, piperidine or pyridine ring, wherein a phenyl residue is fused to the pyridine ring via two adjacent carbon atoms and is a methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring may be substituted by a carbonyl group, optionally in position 1, with an alkyl group of 1 to 3 carbon atoms or a benzyl group substituted with an imidazolyl group attached via a carbon atom additionally optionally substituted on the carbon backbone by an alkyl group of 1 to 3 carbon atoms, optionally an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group substituted imidazolidinedione group, pyridine a zin-3-one or a dihydro-pyridazin-3-one group which, in position 2, may be substituted by a methyl or benzyl group,

R ₇ -NR ₆ -CO-NR ₅ -group in which they represent

R _{5 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, a cyclohexyl or benzyl group,

R _{6 is} a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, an allyl, cyclohexyl, benzyl or phenyl group,

R _? a hydrogen atom or an alkyl group of 1 to 3 carbon atoms or

R ₆ and R _? together with the nitrogen atom lying between them, an alkyleneimine group of 4 to 6 straight carbon atoms or a morpholine group, or

R ₅ and R ₆ together are an alkylene group of 2 or 3 carbon atoms, or

R 1 is a hydrogen atom or in the 5,6 or 7 position of a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms or a trifluoromethyl group, and

Optionally in position 1 with an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, the phenyl nucleus of one of the aforementioned benzimidazole groups being optionally substituted by a fluorine atom, methyl or trifluoromethyl imidazo [2, 1b] thiazol-6-yl, imidazo [1,2-apyridin-2-yl, 5,6,7,8-tetra-hydro-imidazo [1,2-a] pyridin-2-yl , imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] pyridin-2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1,2-c] ] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-cypyridin-2-yl, purin-8 -yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-cypyridazin-2-yl] or imidazo [4,5-d] pyridazin-2-yl, pyrrolidine-linked carbon atom, a piperidine or pyridine ring, wherein a phenyl residue is condensed on the pyridine ring via two adjacent carbon atoms and the methylene group is adjacent to the nitrogen atom in the pyrrolidine or piperidine o the brooxy may be substituted by a carbonyl group, or optionally in position 1 with an alkyl group of 1 to 3 carbon atoms or a benzyl group substituted imidazolyl group via a carbon atom which may additionally be substituted by an alkyl group of 1 to 3 carbon atoms, where, if (v) R 1 is a hydrogen atom, R 8 is a n-butyl group and R _{4 is a} carboxy group, R 2 in position 6 cannot represent a benzimidazol-2-yl group,

R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and

R ₄ carboxy or 1 H -tetrazolyl group, their 1-, 3-isomeric mixtures as well as their salts, in particular for the pharmaceutical use of their physiologically acceptable salts with inorganic or organic acids or bases, unless otherwise stated above alkanoyl, the alkyl or alkoxy moiety may each contain 1 to 3 carbon atoms as well as the aforementioned cycloalkyl moiety may each contain 3 to 7 carbon atoms.

Particularly preferred compounds of the above general formula I are those in which they are understood

Rj in position 4 is a chlorine atom, an alkyl group of 1 to 3 carbon atoms or a trifluoromethyl group, and

R 2 is an alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted with an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted with a benzimidazolyl or tetrahydrobenzimidazolyl group , an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or an N-benzenesulfonylmethylamino group, phthalimino or homophthalimino group, the carbonyl group in the phthalimino group being substituted by a methylene group,

A 5-, 6- or 7-membered alkylimino group in which the methylene group is replaced by a carbonyl or sulfonyl group, a glutamic acid imine group in which the n-propylene group may be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, optionally with an alkyl or phenyl group a mono- or disubstituted imido group of maleic acid, the substituents may be the same or different, optionally in position 1 with an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazole-2- group, wherein the phenyl core of one of the benzimidazole groups mentioned above may be further substituted by a fluorine atom, methyl or trifluoromethyl group, imidase [2, 1b] thiazol-6-yl, imidase [1,2-a] pyridin-2 -yl, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] pyridin-2-yl, imidazo [4,5c] pyridin-2-yl, imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] ] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-c] -pyridin-2-yl, purin-8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl or imidazo [4,5d] pyridazin-2-yl group, via a carbon atom, a pyrrolidine, piperidine or pyridine ring attached to the pyridine ring a phenyl residue condensed through two adjacent carbon atoms and the methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring may be replaced by a carbonyl group, in position 1, with an alkyl group of 1 to 3 carbon atoms, or a benzyl group substituted imidazol-4-yl group, which may additionally be substituted in the carbon framework by an alkyl group of 1 to 3 carbon atoms, a pyridazin-3-one or a dihydro-pyridazin-3-one group which may be substituted in the 2-position by a methyl or benzyl group,

R ₇ -NR ₆ -CO-NR ₅ -group in which they represent

R _{5 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, a cyclohexyl or benzyl group,

R _{6 is} a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, an allyl, cyclohexyl, benzyl or phenyl group,

R _? a hydrogen atom or an alkyl group of 1 to 3 carbon atoms or

R ₆ and R _? together with the nitrogen atom between them an alkylene imine group of 4 to 6 straight carbon atoms or a morpholine group, or

R ₅ and R ₆ together are an alkylene group of 2 or 3 carbon atoms, or

R _{d is} a hydrogen atom or a 5, 6 or 7 alkyl group having 1 to 4 carbon atoms or a trifluoromethyl group, and

R ₂ optionally in position 1 having an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, wherein the phenyl core of one of the aforementioned benzimidazole groups may be further substituted by a fluorine atom, methyl or trifluoromethyl group, imidazo [2, 1b] thiazol-6-yl, imidazo [1,2-a] pyridin-2-yl, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2 -yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] -pyridin-2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1, 2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-c] -pyridin-2 -yl, purin-8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl or imidazo [4,5-d] pyridazin-2-yl a group bonded via a carbon atom to a pyrrolidine, piperidine or pyridine ring, wherein a phenyl residue is condensed to the pyridine ring via two adjacent carbon atoms and the methylene group is adjacent to the nitrogen atom in the pyrrolidine or piperidine may be substituted by a carbonyl group, or in position 1 by an alkyl group of 1 to 3 carbon atoms, or a benzyl group substituted imidazol-4-yl group, which may additionally be substituted in the carbon framework by an alkyl group of 1 to 3 carbon atoms , where, if (v) R 1 represents a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is a} carboxy group, R ₂ in position 6 cannot represent a benzimidazol-2-yl group,

R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and

R _{4 is a} carboxy or tet-tetrazolyl group, in particular those compounds of the above general formula I in which

R ₁ in the 4-position methyl group or a chlorine atom and

R < 2 > is an alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted by an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms which is substituted in the 2, 3, 4 or 5 position with benzimidazolyl or a tetrahydrobenzimidazolyl group, an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or an N-benzenesulfonylmethylamino group, phthalimino or homophthalimino group, wherein the carbonyl group in the phthalimino group may be replaced by a methylene group,

A 5-, 6- or 7-membered alkyleneimino group in which the methylene group is replaced by a carbonyl or sulfonyl group, optionally an alkyl or phenyl group, a mono- or disubstituted imido group of maleic acid, wherein the substituents may be the same or different, in for example in the 1-position with an alkyl group of 1 to 3 carbon atoms substituted benzimidazol-2-yl group, wherein the phenyl core of one of the aforementioned benzimidazole groups can be further substituted with a fluorine atom imidazo {1,2a] pyridine-2 -ylno, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-2-yl or imidazo [2, 1b] thiazol-6-yl a group in position 1 with an alkyl group of 1 to 3 carbon atoms substituted imidazol-4-yl group, pyridazin-3-one or a dihydro-pyridazin-3-one group which may be substituted in methyl 2 with a methyl or benzyl group, or

R _{1 is} a hydrogen atom or a 5,6 or 7 methyl group and

R ^ optionally in position 1 with an alkyl group of 1 to 3 carbon atoms substituted benzimidazol-2-yl group which may be further substituted in the phenyl core by a fluorine atom, in position 1 with an alkyl group of 1 to 3 carbon atoms substituted an imidazol-4-yl group or an imidazo [1,2-a] pyridin-2-yl group, wherein, if (v) R 1 is a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is a} carboxy group, R _{2 is} in position 6 cannot represent the benzimidazol-2-yl group,

R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and

R ₄ carboxy or 1 H -tetrazolyl group, their 1-, 3-isomeric mixtures as well as their salts, in particular for the pharmaceutical use of their physiologically acceptable salts with inorganic or organic acids or bases.

The compounds according to the invention are prepared by the following methods:

a) cyclizing a compound of the general formula

in which they are

Rj and R ₂ as initially defined, one of the residues Χ _χ or Υ _χ represents a group of the general formula

and the second of the residues Χ _χ or Y represents a group of the general formula

- NH ^Z 1 ^Z 2 K / c '- R.

whereby

R ₂ and R ₄ as initially defined,

R _g represents a hydrogen atom or an RgCO group, as defined

R ₃ as previously mentioned,

Z _x and Z ₂ , which may be the same or different, optionally represent substituted amino groups, or optionally lower alkyl groups substituted hydroxy or mercapto groups, or

Ζ _χ and Z ₂ together represent an oxygen or sulfur atom, optionally substituted by an alkyl group of 1 to 3 carbon atoms, an alkylenedioxy or alkylenedithio group each of 2 or 3 carbon atoms, with one of the residues Χ _χ or Υ _χ represent a group of general formula

Cyclization is conveniently carried out in a solvent or solvent mixture, such as ethanol, isopropanol, glacial, benzene, chlorobenzene, toluene, xylene, glycol, glycol monomethyl ether, diethylene glycodimethylether, sulfolane, dimethylformamide, tetraline, or in excess of acylating agent, in general II, e.g. in the corresponding nitrile, anhydride, acid halide, ester or amide, e.g. at temperatures between 0 and 250 ° C, preferably at the boiling point of the reaction mixture, optionally in the presence of a condensing agent such as phosphorous oxychloride, thionyl chloride, sulfuryl chloride, sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, phosphoric acid, phosphoric acid acid, acetic anhydride, or optionally in the presence of a base such as potassium ethylate, or potassium tert.butylate. Cyclization can also be carried out without solvent and / or condensing agent.

Particularly preferably, the reaction is carried out in such a way as to prepare the compound of general formula II into the reaction mixture by reducing the corresponding o-nitro-amino compound, optionally in the presence of a carboxylic acid of the general formula R ₃ COOH or by acylating the corresponding o-diamine compounds. Interrupting the reduction of the nitro group in the hydroxylamine step results in the subsequent cyclization of the N-oxide of the compound of general formula I. The resulting N-oxide is subsequently converted by reduction into the corresponding compound of general formula I.

Subsequent reduction of the N-oxide of formula I thus obtained is preferably carried out in a solvent such as water, water / ethanol, methanol, glacial, ethyl acetic acid or dimethylformamide with hydrogen in the presence of a hydride catalyst such as Raney-nickel, platinum or palladium / charcoal. metals such as iron, tin ah 'zinc, in the presence of acid as acetic acid, hydrochloric acid or sulfuric acid, with salts as ferric (II) sulphate, tin (II) chloride or sodium dithionite, or with hydrazine in the presence of Raney-nickel at temperatures between 0 and 50 ° C, preferably at room temperature.

b) the metabolism of benzimidazole of the general formula

in which they are

R 1 to R ₃ as initially defined, with a biphenyl compound of the general formula

in which it is

R ₄ as initially defined and

Z ₃ represents a nucleophilic leaving group, such as a halogen atom, e.g. a chlorine, bromine or iodine atom, or a substituted sulfonyloxy group, e.g. methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy.

The metabolism is efficiently carried out in a solvent or solvent mixture, such as methylene chloride, diethyl ether, tetrahydrofuran, dioxane, dimethylsulfoxide, dimethylformamide or benzene, as appropriate, in the presence of an acid-binding agent such as sodium carbonate, potassium carbonate, sodium hydroxylate or hydroxyl hydroxide or pyridine, both of which are also used at the same time as a solvent, preferably at temperatures of 0 and 100 ° C, e.g. at temperatures between room temperature and 50 ° C.

Metabolism results in a mixture of 1- and 3-isomers, which are then optionally separated, if desired, by chromatography using a carrier, such as silica gel or alumina, into the corresponding 1- and 3-isomers.

c) for the preparation of a compound of general formula I in which R ₄ represents a carboxy group:

translation of a compound of the general formula

in which they are

Rj to R ₃ as initially defined and

R ₄ 'represents a group which can be converted into a carboxy group by hydrolysis, thermolysis or hydrogenolysis.

Thus, e.g. the functional derivatives of the carboxy group as their unsubstituted or substituted amides, esters, thiol esters, orthoesters, iminoeters, amidines or anhydrides, a nitrile group or a tetrazolyl group is converted by hydrolysis to the carboxy group, esters with tertiary alcohols, e.g. tert.butyl ester is converted by thermolysis to the carboxy group and esters with aralkanols, e.g. the benzyl ester is converted by hydrogenolysis to the carboxy group.

Hydrolysis is carried out as appropriate either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, trichloroacetic acid or trifluoroacetic acid in the presence of a base, such as sodium hydroxide or potassium hydroxide in a suitable solvent such as water, water / methanol, ethanol, ethanol, ethanol, ethanol , water / isopropanol or water / dioxane at temperatures between -10 ° C and 120 ° C, nur. at 'temperatures between room temperature and boiling point of the reaction mixture. Hydrolysis in the presence of certain organic acids, such as trichloroacetic acid or trifluoroacetic acid, may optionally be simultaneously converted to the corresponding acyloxy group, such as trifluoroacetoxy group.

If R ₄ ', in a compound of general formula V, is a cyano or aminocarbonyl group, these groups may also be converted to the carboxy group by nitrite, e.g. sodium nitrite, in the presence of acid, as sulfuric acid, whilst being used simultaneously as a solvent, at temperatures between 0 and 50 ° C.

If R ₄ 'represents a compound of the general formula V e.g. the tert.but'lcksicarbonyl group may also be thermally cleaved in the tert.butyl group, optionally in an inert solvent such as methylene chloride, chloroform, benzene, toluene, tetrahydrofuran or dioxane, and preferably in the presence of a catalytic amount of acid, such as p-toluenesulfonic acid, sulfuric acid, sulfuric acid, sulfuric acid phosphoric acid or polyphosphoric acid, preferably at the boiling point of the solvent used, e.g. at temperatures between 40 ° C and 100 ° C.

If R ₄ 'represents a compound of the general formula V e.g. benzyloxycarbonyl group, the benzyl group may also be hydrolytically cleaved in the presence of a hydride catalyst, such as palladium / charcoal, in a suitable solvent such as methanol, ethanol, ethanol / water, glacial acetic acid, ethyl acetate, dioxane or dimethylformamide, preferably at temperatures between 0 and 50 and 50 C, e.g. at room temperature and hydrogen pressure from 1 to 5 bar. Hydrogenolysis can simultaneously reduce other residues, e.g. a nitro group to an amino group, a benzyloxy group to a hydroxy group, a vinylidene group to a suitable alkylidene group, or a cinnamic acid group to a corresponding phenyl propionic acid group or with a hydrogen atom, for example. halogen atom.

d) For the preparation of a compound of general formula I in which R ₄ represents a 1Htetrazolyl group:

Vaccination of a protective residue from a compound of the general formula

in which they are

R _p R ₂ and R ₃ as initially defined and

R ₄ represents a protected ΙΗ-tetrazolyl group in position 1 or 3 with a protecting residue.

As a protective residue, e.g. triphenylmethyl, tin tributyl or tin triphenyl group.

Vaccination of the protective residue used is preferably carried out in the presence of halogen, preferably in the presence of hydrogen chloride, in the presence of a base such as sodium hydroxide or alcoholic ammonia in a suitable solvent such as methylene chloride, methanol, methanol / ammonia, ethanol or isopropanol at temperatures between 0 and 100 ° C, preferably at room temperature or even if the reaction is carried out in the presence of alcoholic ammonia at elevated temperatures, e.g. at temperatures between 100 and 150 ° C, preferably at temperatures between 120 and 140 ° C.

e) For the preparation of a compound of general formula I in which R ₄ represents a 1Htetrazolyl group:

Metabolism of a compound of the general formula

R, to R ₃ as initially defined, with hydrochloric acid or salts thereof.

The metabolism is preferably carried out in a solvent such as benzene, toluene or dimethylformamide at temperatures between 80 and 150 ° C, preferably at 125 ° C. In this case it is expedient to release either nitric acid during the alkali azide metabolism, e.g. of sodium azide in the presence of a weak acid such as ammonium chloride or a tetrazolyl salt obtained in a mixture when digested with a hydrochloric acid salt, preferably with aluminum azide, or tributyltin azide, which was further conveniently prepared in a reaction mixture with aluminum chloride hydrochloride hydrochloride acid chloride with alkali azide as sodium azide, then released by acidification with dilute acid as 2N hydrochloric acid or 2N sulfuric acid.

f) For the preparation of compounds of the general formula I in which R ₂ represents one of the initially mentioned 2 groups: imidase [1,2-a] pyridin-2-yl, imidase [1,2a] pyrimidin-2-yl, imidase [ 1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl or imidazo [2, 1b] thiazol-6- group:

Metabolism of a compound of the general formula

D 'N, (VIII) nh ₂ in which one of the residues A, B, C or D represents a methine group or a nitrogen atom and the rest of the residues AB, C or D of the methine group or A and B are each a methine group and -C = D -the sulfur atom group,

R ₉ represents aist, hydrogen, fluorine, chlorine or bromine, alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkyoinc :, dialkylamino, alkanoylamino, ck.ro _with carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkhaminocarbonyl, trikhaminocarbonyl, trikylaminocarbonyl, trik an aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group and

R _{10 is} a hydrogen, fluorine or chlorine atom, a methyl, methoxy or hydroxy group, where, when R ₉ and R _{10 are} adjacent methyl groups, they may be linked to a methylene or ethylene group by a compound of the general formula

in which ^R r ^R 3 and R _{4 are} as defined initially and represents

With a ₄ nucleophilic starting group, such as a halogen atom, e.g. chlorine or bromine atom.

Metabolism is conveniently carried out in a solvent or solvent mixture such as ethanol, isopropanol, benzene, glycol, glycol monomethyl ether, dimethylformamide or dioxane, e.g. at temperatures between 0 and 150 ° C, preferably at temperatures between 20 and 100 ° C. Metabolism can also be performed without solvent.

g) For the preparation of compounds of general formula I in which R ₂ represents one of the initially mentioned groups: benzimidazol-2-yl, imidase [4,5-b] pyridin-2-yl, imidase [4,5-c] pyridine -2-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5c] pyridazin-2-yl, imidazo [4,5-d] pyridazin-2-yl or purin-8-yl group:

By cyclizing a compound of the general formula

in which none, one or two of the residues A ^, B _r or the nitrogen atom and the residual residues of residues A ₁ , B _p C _J or D _{3 of the} methine group are represented,

R atom of hydrogen, fluorine, chlorine or bromine, alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethylsulfonyl, alkanoylosulfonyl, alkanoylsulfonyl, alkanoyl and

R _{J2 is} a hydrogen, fluorine or chlorine atom, a methyl, methoxy or hydroxy group, one of the radicals or a Y ₂ R ₁₃ -NH group and the other of a radical of the X ₂ or Y ₂ group of the general formula

wherein R _p R and R ₄ as initially defined, and represent one of the radicals R _J3, or R ₁₄ is a hydrogen atom and the other of the radicals R ₁₃ or R ₁₄ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group,

Z ₅ and Z ₆ , which may be the same or different, optionally substituted amino groups, or optionally lower alkyl groups substituted hydroxy or mercapto groups, or

Z ₅ and Z ₆ together have an oxygen or sulfur atom optionally with an alkyl group of 1 to 3 carbon atoms substituted imino group, an alkyldioxy or alkylenedithio group with 2 or 3 carbon atoms each and then hydrolysis thereafter.

Cyclization is efficiently carried out in a solvent or solvent mixture, such as ethanol, isopropanol, glacial, benzene, chlorobenzene, toluene, xylene, glycol, glycol monomethyl ether, diethylene glycol dimethylether, sulfolane, dimethylformamide, tetralin or in excess of acylating agent with acylating agent formula X, e.g. in the corresponding nitrile, anhydride, acid halide, ester or amide, e.g. at temperatures between 0 and 250 ° C, and preferably at the boiling point of the reaction mixture, optionally in the presence of a condensing agent such as phosphorus oxychloride, thionyl chloride, sulfuryl chloride, sulfuric acid, p-toluenesulfonic acid, methanesulphonic acid, hydrochloric acid, phosphorus , polyphosphoric acid, acetic anhydride, or optionally in the presence of a base such as potassium ethylate or potassium tert.butylate. Cyclization can also be carried out without solvent and / or condensing agent.

Particularly preferably, the reaction is carried out in such a way as to prepare a compound of general formula X into the reaction mixture, by reducing the corresponding o-nitro-amino compound in the present case in the presence of a carboxylic acid of general formula

(XI) wherein ^R p is R ₃ and R ₄ as defined initially, or by acylation of the corresponding o-diamino compound with a carboxylic acid of general formula XI.

Interrupting the reduction of the nitro group in the hydroxyl amine step results in the subsequent cyclization of the N-oxide of the compound of general formula I. The resulting N-oxide is then converted by reduction to the corresponding compound of the general formula I.

Subsequent reduction of the N-oxide thus obtained is preferably carried out in a solvent such as water, water / ethanol, methanol, glacial, ethyl acetate or dimethylformamide with hydrogen in the presence of a hydrating catalyst such as Raney-nickel, platinum or palladium / carbon as metals , tin or zinc in the presence of acid, such as acetic acid, hydrochloric acid or sulfuric acid, with salts such as ferric (II) sulfate, tin (II) chloride or sodium dithionite or hydrazine in the presence of Raney-nickel at temperatures between 0 and 50 And preferably at room temperature.

Subsequent hydrolysis is conveniently carried out either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, trichloroacetic acid or trifluoroacetic acid and in the presence of a base such as sodium hydroxide or potassium hydroxide in a suitable solvent, such as water, water / methanol, water / methanol, ethanol, water / isopropanol or water / dioxane, at temperatures between -10 ° C and 120 ° C, e.g. at temperatures between room temperature and boiling point of the reaction mixture. In the case of hydrolysis in the presence of organic acids such as trichloroacetic acid or trifluoroacetic acid, the alcoholic hydroxy groups present at the same time may simultaneously be converted to the corresponding acyloxy group, such as the trifluoroacetoxy group.

h) For the preparation of compounds of general formula I in which R ₂ represents a dihydropyridazin-3-one or pyridazin-3-one group which may be substituted in position 2, optionally substituted by a phenyl group, substituted alkyl group of 1 to 3 carbon atoms, or may be substituted in the carbon framework by one or two alkyl groups of 1 to 3 carbon atoms each:

Carboxylic acid metabolism of general formula

(XII) in which they are

R 'R- and R' as initially defined and 1 '3 4

E, optionally, with one or two alkyl groups of up to 3 carbon atoms each, substituted ethylene or ethylene ethylene group, or acid derivatives thereof, such as esters, amides or halides thereof, with hydrazine of the general formula

H ₂ N - NHR ₁₅ (XIII) in which

R ₁₅ represents a hydrogen atom or optionally substituted phenyl group with 1 to 3 carbon atoms.

The metabolism is efficiently carried out in a solvent such as methanol, ethanol, isopropanol, glacial acetic acid, propionic acid and / or excess hydrazine or. hydrazine hydrate at temperatures between 0 and 200 ° C, e.g. at temperatures of 20 and 150 ° C, preferably at the boiling point of the reaction mixture and optionally in the presence of an acid such as sulfuric acid or p-toluenesulfonic acid as a condensing agent. Metabolism can also be performed without solvent.

In the case of the metabolites previously described, the reactive groups present, such as hydroxy, amino or alkylamino groups, may be protected during the metabolism by conventional protecting groups which are further cleaved after the metabolism.

As hydroxy protecting groups, e.g. trimethylsilyl, acetyl, benzoyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group and as a protecting group for the amino, alkylamino or imino group, acetyl, benzoyl, ethoxycarbonyl or benzyl group.

In the present case, the subsequent cleavage of the protective residue used is preferably hydrolytic in an aqueous solvent, e.g. in water, isopropanol / water, tetrahydrofuran / water or dioxane / water in the presence of an acid such as hydrochloric acid or sulfuric acid or in the presence of an alkali base such as sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C, preferably at the boiling point of the reaction mixtures. However, the grafting of the benzyl moiety is preferably hydrogenolytic, e.g. with hydrogen in the presence of a catalyst, such as palladium / charcoal in a solvent, such as methanol, ethanol, ethyl ester of acetic acid or glacial acetic acid, optionally when added with acid, as hydrochloric acid at temperatures between 0 and 50 ° C and preferably at room temperature and pressure hydrogen 1 to 7 bar, preferably 3 to 5 bar.

The thus obtained isomer mixture of a compound of the general formula I can be optionally separated chromatographically using a carrier such as silica gel or alumina.

Furthermore, the compounds of the general formula I thus obtained can be converted into their acid addition salts, in particular for pharmaceutical use, into their physiologically acceptable salts with inorganic or organic acids. As acids, therefore, e.g. hydrochloric acid, hydrobromic acid, sulfuric acid, - phosphoric acid, fumaiic acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

In addition, the new compounds of general formula I are thus obtained, provided that they contain a carboxy or 1H-tetrazolyl group, if desired, subsequently converted into their salts with inorganic or organic bases, in particular for pharmaceutical use, into their physiologically acceptable salts. As bases, for example, they come in handy. sodium hydroxide, potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of general formulas II to XIII that are used as starting materials are partially known from the literature or obtained by methods known from the literature.

So we get e.g. a compound of the general formula II by alkylating the corresponding o-aminonitro compound and subsequently reducing the nitro group.

Compounds of the general formulas III V, VI, VII, IX, X ah XII, which: λ is used as starting material, are obtained by acihria of the corresponding o-femlendium mna or the corresponding o-aminonitro compounds, subsequent reduction of the nitro group and subsequent cyclization of the thus obtained o -diaminophenyl compounds and, optionally, subsequent vaccination of the protective residue used, or by cyclization of the appropriately substituted benzimidazole with the corresponding amine or NH-alkylation of the corresponding 1H-benzimidazole, whereby the isomer mixture thus obtained can then be separated by conventional methods, e.g. by chromatography. The starting compounds mentioned above are partially described in EP-A0 392 317.

So e.g. 2-n-butyl-5- (inridazo [1,2-a] pyridin-2-yl) -3H-benzimidazole with pres34-new p-amino-acetophenone is obtained with butyric acid chloride, subsequent nitration, bromination, cyclization with 2- aminopyridine in 6-n-butanoylamido-3 (imidase [1,2-a] pyridin-2-yl) nitrobesene, which is subsequently converted by cyclization to the desired compound after reduction of the nitro group or

2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -1H-benzimidazole by nitration of 3-methyl-4-n-butanoylamido-benzoic acid methyl ester, subsequent reduction of the nitro group and cyclization in 2 -n-butyl-4-methyl-6-methoxycarbonyl-1H-benzimidazole, which is then converted with 2-methylamino-aniline by cyclization to the desired compound.

Benzimidazole in which the alkoxy group in position 2, 3, 4 or 5 is substituted by an imidazole moiety is obtained e.g. by the metabolism of the corresponding 7-hydroxy-benzimidazole described in EP-A-0 392 317, by the metabolism with the corresponding α, ω-dihalogenalkane and the subsequent metabolism by the corresponding imidazole.

Novel compounds of general formula I and their physiologically tolerable salts have valuable pharmacological properties. These represent angiotensin antagonists, in particular angiotensin-II antagonists.

For example, we are compounds

A = 4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methylbenzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid,

B = trifluoroacetate 4′- [[2-n-butyl-7- [3- (imidazo-1-yl) -propyloxy] -4-methylbenzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid,

C - 4 '- [[2-n-butyl-4-methyl-7- [4- (tetrahydrobenzimidazol-1-yl) -butyloxy] -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid,

D = 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid,

E = 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl) -biphenyl ,

F = 4 '- [[2-n-propyl-4-methyl-6- (1-oxo-isoindolin-2-yl) -benziniidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl,

G = 4 '- [[2-n-propyl-4-methyl-6- (butansultam-1-yl) -benziniidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl,

H = semihirate 4 '- [[2-n-butyl-6- (2,3-dimethylmaleic acid imino) -4-methylbenzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid,

I = 4 '- [[2-n-butyl-6- (isopropylcarbonylamino) -4-methyl-benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid,

J = 4 '- [[2-n-butyl-4-methyl-6- (morpholinocarbonylamino) -benzimidazol-lyl] -methyl] -biphenyl-2-carboxylic acid,

K = semitrifluoroacetate 4 '- [[2-n-butyl-6- (cyclohexylaminocarbonylamino) -4-methyl benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid,

L = 4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5 -yl) -biphenyl,

M = 4 '- [(2-cyclopropyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid,

N = 4 '- [(2-n-propyl-4-methyl-6- (1-methyl-5-fluoro-benzimidazol-2-yl) -i-enzymidazolyl-yl) -methyl] -biphenyl-2-carboxyl acid,

O = 4'- [(2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl) phenyl] -2- (1H-tetrazole -5-yl) -biphenyl,

P = 44 (2-η-ρΐΌρΐ1-4-ιη6ίΠ-6- (5,6,7,8-ίβύ · 3ΐ ± 1ΐΌ-ΐπη ^ 3Ζ0- [1,2-3] ρπΊάΐη-2-ΐ1) bezimidazole- 1-yl) -methyl] -biphenyl-2-carboxylic acid, = 4 '- [(2-n-propyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2- a] Pyridin-2-yl) 36 benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, r = 4 '- [(2-n-propyl-4-chloro- 6- (1-methylbenzimidazol-2-yl) benzimidazol-1-yl) -methyl] 2- (1H-tetrazol-5-yl) -biphenyl-hydrochloride and

S = 4 '- [[2-n-propyl-4-methyl-6- (imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid their biological effects are as follows:

Description of the Angiotensin II Receptor Binding Method

The tissue (rat lung) was homogenized in tris buffer (50 mmol tris, 150 mmol NaCl, 5 mmol EDTA, pH 7.40) and centrifuged twice at 2000 x g for 20 minutes. The pellets were definitively suspended in incubation buffer (50 mmol tris, 5 mmol MgCl 2, 0.2% BSA, pH 7.40) 1:75, based on the weight of tissue moisture. After 0.1 ml of homogenate, incubate for 60 minutes at 37 ° C with 50 pM [125 ^ -angiotensin II (NEN, Dreieich, FRG) and increasing concentrations of the test substance in a total volume of 0.25 ml. The incubation is completed by rapid filtration through a glass fiber filter pad. The filter was washed with 4 ml of ice-free buffer (25 mmol tris, 2.5 mmol MgCl ₂ , 0.1% BSA, pH 7.40). The bound radioactivity is determined in a gamma counter. From the dose-effect curve, determine the appropriate IC _{5 ()} value.

Substances A to S show the following IC ₅₀ values in the test described:

Substance IC ₅₀ [nM] A 510,0 B 52,0 C 130.0 D 3.7 E 14,0 F 5.0 Mr 1,2

Η

I

J

K

L

M

N

Oh

P

Q

R

S

20,0

6.6

3.5

17,0

240,0

12,0

26,0

3.4

1,2

1.7 20,0

7.8

We additionally test compounds D, E, F, G, H, M, and O on awake renal hypertensive rats for their effect after oral administration, according to methods known in the literature. At a dose of 10 mg / kg, the compounds show the effect of lowering blood pressure.

Furthermore, no administration of the above compounds up to a dose of 30 mg / kg i.v. no toxic side effects, e.g. no negative inotropic effect and no disturbance of heart rhythm. The compounds are therefore well tolerated.

Based on their pharmacological properties, novel compounds and their physiologically tolerable salts are suitable for the treatment of hypertension and heart failure, further for the treatment of ischemic peripheral circulation disorders, myocardial ischemia (angina), for the prevention of progression of heart failure after myocardial infarction, for the treatment of diabetic nephropathy , gastrointestinal and bladder disorders.

Furthermore, novel compounds and their physiologically tolerable salts are suitable for the treatment of pulmonary diseases, e.g. pulmonary edema and chronic bronchitis, for the prevention of arterial restenosis after angiplasty, vascular wall thickening after vascular surgery, arteriosclerosis, and diabetic angiopathy. Due to the effect of angiotensin on the release of acetyl choline and dopamine in the brain, novel angiotensin antagonists are also suitable for the elimination of CNS disorders, e.g. depression, Alzheimer's disease,

Parkinson's syndrome, bulimia as well as disorders of cognitive function.

The dosage required to achieve an appropriate effect in adults is preferably 20 to 100 mg, preferably 30 to 70 mg, intravenously, and 50 to 200 mg, preferably 75 to 150 mg, of oral administration 1 to 3 times daily. To this end, the compounds of general formula I prepared according to the invention are optionally administered in combination with other effective substances, such as e.g. blood pressure lowerers, diuretics and / or calcium antagonists, together with one or more inert conventional carriers and / or diluents, e.g. with maize starch, milk sugar, raw sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / glycerin, water / sorbitol, water / polyethylene glycol, propylene glycol ethylene glycol, propylene ethylene glycol, containing fat as solid fat or their suitable mixtures, incorporated into conventional galenic preparations such as tablets, dragees, capsules, powders, suspensions or suppositories.

For the aforementioned combinations, further effective substances are therefore contemplated, e.g. bendroflumethiazide, chlorothiazide, hydrochlorothiazide, spironolactone, benzthiazide, cyclothiazide, etacric acid, furosemide, metoprolol, prazosin, atenolol, propranolol, (di) hydralazine hydrochloride, diltiazem, felodipine, nicardipine nitridipine, nicodipine, nicodipine, nicodipine, nicodipine, nicardipine. The dose for these active substances is therefore 1/5 of the normal recommended minimum dosage up to 1/1 of the normal recommended dosage, ie e.g. 15 to 200 mg of hydrochlorothiazide, 125 to 2000 mg of chlorothiazide, 15 to 200 mg of etacric acid, 5 to 80 mg of furosemide, 20 to 480 mg of propranolol, 5 to 60 mg of felodipine, 5 to 60 mg of nifedipine or 5 to 60 mg of nitrendipine.

The following examples should explain the invention more closely:

EXAMPLES

4 '- [[2-n-Butyl-7- [5- (imidazol-1-yl) -pentyloxy] -4-methyl-benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid hydrate

0.7 g (1.15 mmol) of tert-butyl ester 4 '- [[2-n-butyl-7- [5- (imidazol-1-yl) -pentyloxy] 4-methyl-benzimidazol-1-yl] - Methyl] -biphenyl-2-carboxylic acid was dissolved in 35 ml of methylene chloride, 5 ml of trifluoroacetic acid were added and stirred at room temperature for 12 hours. Dilute with methylene chloride and shake with water and with saturated sodium bicarbonate solution. The organic phase was dried over sodium sulfate and evaporated in vacuo. The crude product thus obtained was purified over a silica gel column (grain size: 0.063-0.02 mm, ethyl acetate / ethanol / ammonia = 90: 10: 0.1) and crystallized from acetone.

Yield: 0.19 g (29.9% of theory), mp 185-187 ° C

C ₃₄ H _3g N ₄ O ₃ x H ₂ O (550.70) calc .: C 71.81 H 7.09 N 9.85 found: 72.03 7.19 9.71 mass spectrum: m / e = M ⁺ 550

Analogous to Example 1, the following compounds are obtained:

4 '- [[2-n-butyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-ylmethyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-yl] methyl] -biphenyl-2- carboxylic acid

4 '- [[2-ethyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (phenylaminocarbonylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-ethyl-4-methyl-6- (cyclohexylaminocarbonylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (cyclohexylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-methylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (n-pentylaminocarbonyl-methylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (n-pentylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (n-butylaminocarbonyl-methylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (benzylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (allylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl] -methyl-amino) -benzimidazolyl-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (dimethylaminocarbonyl-phenyl-amino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl · 4-methyl-6- (dimethylaminocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl-n-butylamino) -benzimidazolyl-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-cyclohexylamino) -benzimidazolyl-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-benzylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-pyrrol-4-methyl-6- (n-hexylaminocarbonyl-cyclohexylamino) -benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl-ethylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (dimethylaminocarbonyl-n-pentylamino) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (morpholinocarbonylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (pyrrolidinocarbonylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (pyrrolidinocarbonyl-methylamino) -benziniidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (piperidinocarbonylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinon-1-yl) benzimidazol-1-yl] - methyl] -biphenyl-2-carboxylic acid.

EXAMPLE 2

4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [3 (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl] tert-butyl ester] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 69.4% of theory.

mp .: 208-210 ° C (522.64) calcd .: C 73.54 H 6.56 N 10.72 found: 73.45 6.62 10.60

R _f -value: 0.50 (silica gel; ethyl acetate / ethanol / ammonia = 50: 45: 5)

EXAMPLE 3

4 '- [[2-n-Butyl-7- [3- (benzimidazol-1-yl) -propyloxy] -4-methylbenzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid trifluoroacetate

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [3- (benzimidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl] tert-butyl ester] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 87.8% of theory.

M.p .: 221-223 ° C x CF ₃ COOH (686.72) Calc .: C 66.46 H 5.43 N 8.15 Found .: 66.58 5.62 8.31

R _f -value: 0.5 (silica gel; ethyl acetate / ethanol / ammonia - 50: 45: 5)

EXAMPLE 4

4 '- [[2-n-Butyl-7- [4- (imidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid hydrate

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [4- (imidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] -methyl] - tert-butyl ester] - biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 68.5% of theory.

Mp: 126-128 ° C

C ^ H ^ O ^ 1/0 (554.68) calc .: C 71.46 H 6.91 N 10.10 Found: 71.63 7.02 9.98 Mass spectrum: m / e = 536

EXAMPLE 5

4 '- [[2-n-butyl-7- [2- (benzimidazol-1-yl) -ethoxy] -4-methyl-benzimidazol-1-yl] -methyl] ~ biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-Butyl-7- [2- (benzimidazol-1-yl) -ethoxy] -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl tert-butyl ester. -2 Carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 78.1% of theory.

M.p .: 167-169 ° C

0 ^^ 0 / 558.68) calc .: C 75.25 H 6.13 N 10.03 found: 75.03 6.17 9.95

EXAMPLE 6

4 '- [[2-n-butyl-7- [5- (benzimidazol-1-yl) -pentyloxy] -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-Butyl-7- [5- (benzimidazol-1-yl) -pentyloxy] -4-methyl-benzimidazol-1-yl] -methyl] biphenyl- tert-butyl ester. 2-carboxylic acids and trifluoroacetic acids in methylene chloride.

EXAMPLE 7

4 '- [[2-n-butyl-7- [4- (benzimidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [4 (benzimidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] -methyl] - tert-butyl ester] - biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

EXAMPLE 8

4 '- [[2-n-butyl-4-methyl-7- [4- (tetrahydrobenzimidazol-1-yl) -butyloxy] -benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert.butyl ester

4 '- [[2-n-butyl-4-methyl-7- [4- (tetrahydrobenzimidazol-1-yl) -butyloxy] -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride . Yield: 86% of theory.

M.p .: 229-231 ° C

C ₃₇ H ₄₂ N ₄ O ₃ (590.76) Calc .: C 75.23 H 7.17 N 9.48 Found: 75.34 7.06 9.38

EXAMPLE 9

4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2- carboxylic acids and trifluoroacetic acids in dimethylformamide.

Yield: 63.9% of theory.

M.p .: 261-263 ° C (^, Η ^ Ν, Ο, (514.60) calcd .: C 77.02 H 5.87 found: 76.90 5.85

N, 10.89; 10.99

Analogous to Example 9, the following compounds are obtained:

4 '- [[2-n-propyl-4-methyl-6- (1-n-propylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-n-hexylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-cyclopropylbenzimidazol-2-yl) -benzimidazol-1-ylmethyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-cyclohexylbenzimidazol-2-yl) benzimidazol-1-ylmethyl] -biphenyl-2-carboxylic acid.

EXAMPLE 10

4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl) -biphenyl

To a solution of 1.60 g (3.3 mmol) of 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2yl) -benzimidazol-1-yl] -methyl] -2-cyano -Biphenyl in 50 ml of dimethylformamide was added 4.3 g (66 mmol) of sodium azide and 3.5 g (66 mmol) of ammonium chloride and the mixture was stirred at 140 ° C for 24 hours. Water is then added and the precipitate is filtered off. The crude product thus obtained is chromatographically purified over silica gel (300 g silica gel, methylene chloride + 6% ethanol).

Yield: 900 mg (51% of theory)

Tal. Mp 228-230 ° C

C ^ H ^ Ng (538.70) calcd .: C 73.58 H 5.61 N 20.80 Found: 73.48 5.55 20.70

The following compounds are obtained analogously to Example 10:

4 '- [[2-n-propyl-4-methyl-6- (1-n-hexylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (1-cyclobutylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl]

2- (1H-Tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (1-cyclohexylbenzimidazol-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [2- (imidazol-1-yl) -ethoxy] -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [4- (imidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [5- (imidazol-1-yl) -pentyloxy] -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [2- (benzimidazol-1-yl) -ethoxy] -4-methyl-benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [3- (benzimidazol-1-yl) -propyloxy] -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [4- (benzimidazol-1-yl) -butyloxy] -4-methyl-benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [5- (benzimidazol-1-yl) -pentyloxy] -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [2- (4,5,6,7-tetrahydrobenzuidazol-1-yl) -ethyloxy] -4-methyl benzimidazol-1-yl] -methyl] -2- (1H-Tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [3- (tetrahydrobenzimidazol-1-yl) -propyloxy] benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-7- [4- (tetrahydrobenzimidazol-1-yl) -butyloxy] -4-methylbenzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-7- [5- (tetrahydrobenzimidazol-1-yl) -pentyloxy] benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (phenylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-ethyl-4-methyl-6- (cyclohexylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-propyl-4-methyl-6- (cyclohexylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (cyclohexylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (n-pentylaminocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (n-pentylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

44 [2-N-Propyn-4-methyl-6- (n-butylaminocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (benzylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (allylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (dimethylaminocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (dimethylaminocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl-n-butylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-cyclohexylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -buffer 1

4 '- [[2-n-propyl-4-methyl-6- (methylaminocarbonyl-benzylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (n-hexylaminocarbonyl-cyclohexylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (cyclohexylaminocarbonyl-ethylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (dimethylaminocarbonyl-n-pentylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (morpholinocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (pyrrolidinocarbonylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '' [[2-n-propyl-4-methyl-6- (pyrrolidinocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (piperidinocarbonyl-methylamino) benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinon-1-yl) benzimidazol-1-yl] - methyl] -2- (1H-tetrazol-5-yl) -biphenyl

EXAMPLE 11

4 '- [[2-n-propyl-4-methyl-6-phthalimino-benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepare analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6-phthalimino benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 6.8% of theory.

Melting point: above 160 ° C sintering (553.60) Calc .: C 71.59 H 4.92 N 17.71 Found: 71.39 4.88 17.54

EXAMPLE 12

4 '- [(2-n-butyl-4-methyl-6-phthalimino-benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-butyl-4-methyl-6-phthalimino-benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 7.1% of theory.

Melting point: above 150 ° C sintering (567.70) Calc .: C 71.94 H 5.15 N 17.27 Found: 71.75 5.19 17.22

EXAMPLE 13

4 '- [[2-n-propyl-4-methyl-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl] -methyl 2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (1-oxo isoindolin-2-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide \ dimethylformamide.

Yield: 25.0% of theory.

Melting point: above 170 ° C sintering

C ₃₃ H2 ₉ N ₇ O (539.60) calcd .: C 73.45 H 5.42 N 18.17 found: 73.20 5.41 18.33

EXAMPLE 14

4 '- [[2-n-butyl-4-methyl-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (1-oxo-isoindolin 2-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 21.0% of theory.

Melting point: above 165 ° C sintering

0 ^^ 0 (553.70) calculated: C 73.76 H 5.64 N 17.71 found: 73.58 5.33 17.41

EXAMPLE 15

4 '- [[2-n-propyl-4-methyl-6- (butanesultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide .

Yield: 49.0% of theory.

Melting point: above 186 ° C sintering

0 ^^ 028 (541.70) calcd .: C 64.30 H 5.77 N 18.10 S 5.92 found: 64.10 5.39 18.01 5.98

EXAMPLE 16

4 '- [[2-ethyl-4-methyl-6- (butanesultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-ethyl-4-methyl-6- (butansultam-1-yl) benzimidazol-1-yl] methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 60.0% of theory.

Melting point: amorphous above 194 ° C sintering

C ^ N ^ S (527.70) calc .: 0 63.74 H 5.54 N 18.58 S 6.08 found: 63.83 5.66 18.41 5.82

EXAMPLE 17

4 '- [[2-n-butyl-4-methyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared in analogy as in Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (butansultam-1-yl) benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 48.0% of theory.

Melting point: amorphous above 183 ° C sintering

C ^ N / S (555.70) calculated: C 64.84 H 5.99 N 17.64 S 5.77 found: 64.53 5.66 17.63 5.55

EXAMPLE 18

4 '- [[2-n-propyl-4-ethyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-ethyl-6- (butansultam-1-yl) benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 27.0% of theory.

Melting point: amorphous above 189 ° C sintering

C ^ N ^ S (555.70) calcd .: C 64.84 H 5.99 N 17.64 S 5.77 found: 64.81 5.68 17.87 5.31

EXAMPLE 19

4 '- [[2-ethyl-4-ethyl-6- (butanesultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [[2-ethyl-4-ethyl-6- (butansultam-1-yl) benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 39.0% of theory.

Melting point: amorphous above 212 ° C sintering C ₂₉ H ₃₁ N ₇ O ₂ S (541.70) calcd: C 64.30 H 5.77 N 18.10 found: 64.30 5.51 17.99

S, 5.92 5.59

EXAMPLE 20

4 '- [[2-n-propyl-4-isopropyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared in analogy as in Example 10 from 4 '- [[2-n-propyl-4-isopropyl-6 (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 22.0% of theory.

M.p .: amorphous

C ₃₁ H ₃₅ N ₇ O ₂ S (569.70) calcd .: C 65.35 H 6.19 N 17.21 S 5.63 found: 65.13 6.10 17.54 5.40

EXAMPLE 21

4 '- [[2-ethyl-4-isopropyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared in analogy as in Example 10 from 4 '- [[2-ethyl-4-isopropyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 24.0% of theory.

Melting point: amorphous, above 209 ° C sintering (555.70) calculated: C 64.84 H 5.99 N 17.64 S 5.77 found: 64.99 5.71 17.43 5.71

EXAMPLE 22

4 '- [[2-n-propyl-4-trifluoromethyl-6- (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2 (1H-tetrazol-5-yl) -biphenyl

Prepared in analogy to Example 10 from 4 '- [[2-n-propyl-4-trifluoromethyl-6 (butansultam-1-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 17.0% of theory.

Mp .: 199-203 ° C (595.70) Calcd .: C 58.48 H 4.74 N 16.46 Found: 58.28 4.43 16.22

EXAMPLE 23

4 '- [[2-n-propyl-4-methyl-6- (N-benzenesulfonyl-methylamino) -benzimidazol-1-yl] -methyl-2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (N-benzenesulfonyl-methylamino) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide .

Yield: 42.0% of theory.

M.p .: 161-163 ° C

C ^ NAS (577.70) calcd .: C 66.53 H 5.41 N 16.97 S 5.55 found: 66.32 5.36 16.70 5.31

EXAMPLE 24

4 '- [[2-n-butyl-4-methyl-6- (N-benzenesulfonyl-methylamino) -benzimidazol-1-yl] -methyl] ~

2- (1H-Tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (N-benzenesulfonyl-methylamino) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 37.0% of theory.

M.p .: 150-153 ° C

C ₃₃ H ₃₃ N ₇ O ₂ S (591.70) calcd .: C 66.98 H 5.62 N 16.57 found: 66.71 5.38 16.39

Analogous to Example 24, the following compounds are obtained:

4 '- [[2-ethyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazole -5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-ylmethyl] -2- (1H-tetrazole -5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (4,5-dihydro-2H-pyridazin-3-one-6-yl) -benzimidazol-1-yl] methyl] -2- (1H -tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyridininon-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-ethyl-4-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinon-1-yl) -benzimidazol-1-yl] -methyl ] -2- (1H-tetrazol-5-yl) -biphenyl

EXAMPLE 25

4 '- [[2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxyl tert-butyl ester acids and trifluoroacetic acids in methylene chloride.

Yield: 48.0% of theory.

Mp .: 233-235 ° C (528.70) Calcd .: C 77.25 H 6.10 N 10.60 Found: 77.10 5.98 10.46

EXAMPLE 26

4 '- [[2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 41.0% of theory.

M.p .: 235-237 ° C

0 ^^ (552.70) Calc .: C 73.89 H 5.84 N 20.28 Found: 73.67 5.81 19.93

Analogous to Example 26, the following compounds are obtained:

4 '- [[2-n-butyl-4-methyl-6- (1-ethyl-benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (1-cyclopropylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (1-n-pentylbenzimidazol-2-yl) -benzimidazol-1-ylmethyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (1-cyclopentylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl

EXAMPLE 27

4 '- [[2-n-propyl-4-methyl-6- (2-oxo-piperidin-1-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) - biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (2-oxo-piperidin-1-yl] benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 51.0% of theory.

Melting point: amorphous, above 140 ° C sintering (505.60) calculated: C 71.26 H 6.18 N 19.39 Found: 71.08 6.22 19.47

EXAMPLE 28

4 '- [[2-n-butyl-4-methyl-6- (2-oxo-piperidin-1-yl) -benzimidazol-1-yl] -methyl] -2 (1H-tetrazol-5-yl) - biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (2-oxo-piperidinyl-yl] -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and of sodium azide in dimethylformamide.

Yield: 39.0% of theory.

Melting point: amorphous, above 128 ° C sintering

C ₃₁ H ₃₃ N ₇ O (519.70) Calc .: C 71.65 H 6.40 N 18.87 Found: 71.44 6.23 18.59

EXAMPLE 29

4 '- [[2-n-propyl-4-methyl-6- (2-oxo-piperidin-1-yl) -benzimidazol-1-yl] -methyl] -2 (1H-tetrazol-5-yl) - biphenyl

Prepared from 4 '- [[2-n-propyl-4-methyl-6- (2-oxo-piperidin-1-yl) -benzimidazol-1-yl] methyl] -2- (2-triphenylmethyl-tetrazol-5 -yl) -biphenyl by cleaving triphenylmethyl group with methanolic hydrochloric acid.

Yield: 51.0% of theory.

Melting point: amorphous, above 115 ° C sintering

C ^ H ^ O (505.60) calcd .: C 71.26 H 6.18 N 19.39 found: 71.51 6.39 19.09

EXAMPLE 30

4 '- [[2-n-propyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-propyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] - tert-butyl ester] - biphenyl-2carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 54.0% of theory.

Mp .: 202-204 ° C (486.60) Calcd .: C 76.52 H 5.39 N 11.52 Found: 76.33 5.32 11.30

Analogous to Example 30, the following compounds are obtained:

4 '- [[2-n-propyl-6- (8-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-6- (6-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (5,7-dimethyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (6-aminocarbonyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-6- (6-chloro-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl2-carboxylic acid

4 '- [[2-n-propyl-6- (imidazo [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-6- (2,3-dimethyl-imidazo [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] 59 biphenyl-2-carboxylic acid

EXAMPLE 31

4 '- [[2-n-butyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] - tert-butyl ester] - biphenyl-2carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 41.0% of theory.

M.p .: 193-195 ° C

0 ^^ 0, (500.60) calcd. C 76.78 H 5.64 N 11.19 Found: 76.73 5.48 11.00

EXAMPLE 32

4 '- [[2-n-propyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [[2-n-propyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl, and of sodium azide in dimethylformamide.

Yield: 28.0% of theory.

M.p .: 187-189 ° C

0 ^^ (510.60) calc .: 0 72.92 H 5.13 N 21.95 found: 72.80 4.97 21.74

Analogous to Example 32, the following compounds are obtained:

4 '- [[2-n-propyl-6- (7-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5 -yl) -biphenyl

4 '- [[2-n-propyl-6- (5-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] 60

2- (1H-Tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-6- (6-bromo-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5 -yl) -biphenyl

4 '- [[2-n-propyl-6- (5,7-dimethyl-imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazole- 5-yl) -biphenyl

4 '- [[2-n-butyl-6- (3-methyl-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl 2- (1H-tetrazol-5-yl) - biphenyl

4 '- [[2-n-propyl-6- (2-phenyl-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl ) -biphenyl

EXAMPLE 33

4 '- [[2-n-butyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-butyl-6- (imidazo- [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 23.0% of theory.

M.p .: 170-173 ° C

C ^ H ^ Ng (524.60) calcd .: C 73.26 H 5.38 N 21.36 found: 73.09 5.32 21.20

EXAMPLE 34

4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methylbiphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] - methyl] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 38.0% of theory.

Melting point: 195-197 ° C (after solvent evaporation)

Melting point: 299-303 ° C (methylene chloride / methanol = 20: 1)

C ₃₂ H ₂₄ N ₄ O ₂ (500.60) calcd: C 76.78 H 5.64 N 11.19 Found: 76.55 5.61 10.87

Analogous to Example 34, the following compounds are obtained:

4 '- [[2-n-propyl-4-methyl-6- (8-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2- carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (7-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2- carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (6-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2- carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (5-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2- carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (5,7-dimethyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2 -carboxylic acid

4 '- [[2-ethyl-4-methyl-6- (6-aminocarbonyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-ethyl-4-methyl-6- (6-chloro-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid

EXAMPLE 35

4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5 -yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] - 2cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 21.0% of theory.

Melting point: above 181 ° C sintering

C ^ N, (524.60) calcd .: C73.26 H 5.38 N 21.36 found: 73.10 5.24 21.13

Analogous to Example 35, the following compounds are obtained:

4 '- [[2-n-propyl-4-methyl-6- (5-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H- tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5 -yl) -biphenyl

EXAMPLE 36

4 '- [[2-n-butyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [[2-n-butyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazo] -1-yl] -methyl] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 51.0% of theory.

Mp .: 194-197 ° C Calc .: C 77.02 H 5.88 N 10.89 Found: 76.81 5.78 10.64

Analogous to Example 36, the following compounds are obtained:

4 '- [[2-n-propyl-6- (pyrrolidin-2-one-5-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (pyrrolidin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (quinolin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-6- (quinolin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-6- (isoquinolin-3-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-ethyl-6- (isoquinolin-3-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

EXAMPLE 37

4 '- [[2-n-butyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5 -yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [[2-n-butyl-4-methyl-6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] - 2cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 26.0% of theory.

^C 33 ^H 30 ^N g ( ⁵ 38.60) calc .: C 73.58 H 5.61 N 20.80 Found: 73.39 5.40 20.92

Analogous to Example 37, the following compounds are obtained:

4′- [[2-n-propyl-6- (pyrrolidin-2-one-5-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol64)

5-yl) -biphenyl

4 '- [[2-n-propyl-6- (pyrrolidin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-propyl-6- (piperidin-2-one-6-yl) -benzimidazo] -1-yl] -methyl] -2- (1H-tetrazol5-yl) -biphenyl

4 '- [[2-n-butyl-6- (piperidin-2-one-6-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol5-yl) -biphenyl

4 '- [[2-n-propyl-6- (piperidin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-butyl-6- (piperidin-2-yl] -benzimidazol-1-yl]] -methyl] -2- (1H-tetrazo] -5-yl] biphenyl

4 '- [[2-ethyl-6- (pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [[2-n-propyl-6- (pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-butyl-6- (pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-propyl-6- (quinolin-2-yl) -benzimidazol-1-yl] -methyl]' 2 '(1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-butyl-6- (quinolin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-n-propyl-6- (isoquinolin-3-yl] -benzimidazo] -1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

4 '- [[2-ethyl-6- (isoquinolin-3-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) biphenyl

EXAMPLE 38

4 '- [[2-n-butyl-4-methyl-6- (2,2-dimethylpropionylamino) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-4-methyl-62,2-dimethylpropionylamino) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid acids in methylene chloride.

EXAMPLE 39

4 '- [[2-n-butyl-7- [2- (tetrahydrobenzimidazol-1-yl) -ethoxy] -4-methyl-benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [2- (tetrahydrobenzimidazol-1-yl) -ethoxy] -4-methyl-benzimidazol-1-yl] -methyl tert-butyl ester] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 81% of theory.

Mp .: 236-237 ° C ^^ 0, (562.71) Calcd .: C 74.71 H 6.81 N 9.96 Found: 74.51 6.79 9.98

EXAMPLE 40

4 '- [[2-n-butyl-4-methyl-7- [5- (tetrahydrobenzimidazol-1-yl) -pentyloxy] benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-4-methyl-7- [5- (tetrahydrobenzimidazol-1-yl) -pentyloxy] -benzimidazol-yl] -methyl] -biphenyl tert-butyl ester -2-carboxylic acids and trifluoroacetic acids in methylene chloride.

EXAMPLE 41

4 '- [[2-n-butyl-7- [3- (tetrahydrobenzimidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-7- [3- (tetrahydrobimidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl tert-butyl ester] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

EXAMPLE 42

4 '- [[2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [[2-n-propyl-4-methyl-6 (imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl] -methyl ] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 47% of theory.

Melting point: 224-226 ° C (after solvent evaporation)

M.p .: 294-297 ° C (methylene chloride / ethanol = 20: 1)

C ₃₁ H2 ₇ N ₅ O ₂ (501.60) calc .: C 74.23 H 5.43 N 13.96 found: 74.10 5.31 13.66

EXAMPLE 43

4 '- [[2-n-propyl-4-methyl-6- (imidazole [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-propyl-4-methyl-6- (imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] tert-butyl ester] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 43% of theory.

Melting point: 192-195 ° C (after solvent evaporation)

Melting point:> 300 ° C (methylene chloride / ethanol = 20: 1)

C ^ NN ^S (506.64) calcd: C 71.12 H 5.17 N 11.06 S 6.33 found: 70.97 5.19 10.88 6.09

Analogous to Example 43, the following compounds are obtained:

4 '- [[2-n-prop3-4-methyl-6- (3-methyl-imidazo [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxyl. acid

4 '- [[2-n-propic4-methyl-6- (2,3-dimethyl-imidazo [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (2,3-tetramethylene-imidazo [2, 1b] -thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2- carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (2,3-trimethylene-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxyl acid

4 '- [[2-ethyl-4-methyl-6- (2-phenyl-imidazo [2, 1-b] thiazol-6-yl) -benzimidazol-1-yl] -ethyl] biphenyl-2-carboxylic acid

EXAMPLE 44

4 '- [[2-n-propyl-4-methyl-6- (imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) -il) -bifeml

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (imidazo [2, 1b] thiazol-6-yl) -benzimidazo] -1-yl] -methyl] -2 -cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 21% of theory.

Melting point: amorphous, above 196 ° C sintering

C ₃ 0 ^H 26 ^N 8 ^S (W7) calcd .: C 67.90 H 4.94 N 21.12 S 6.04 found: 67.77 4.84 21.00 5.87

Analogous to Example 44, the following compounds are obtained:

4 '- [[2-n-propyl-4-methyl-6- (3-methyl-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazole- 5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (2,3-dimethyl-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -2- (1H- tetrazol-5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (2,3-trimethylene-imidazo [2, 1b] thiazol-6-yl) -benzimidazolyl-yl] -methyl] -2- (1H- tetrazol-5-yl) -biphenyl

4 '- [[2-ethyl-4-methyl-6- (2,3-tetramethylene-imidazo [2, 1b] thiazol-6-yl) -benzimidazolyl-yl] -methyl] -2- (1H-tetrazole- 5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (2-phenyl-imidazo [2, 1b] thiazol-6-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazole -5-yl) -biphenyl

EXAMPLE 45

4 '- [[2-n-propyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -2-cyano-biphenyl and sodium azide in dimethylfor mamidu.

Yield: 28% of theory.

Mp .: 202-205 ° C Calc .: C 73.26 H 5.38 'N 21.36 Found: 73.01 5.22 21.56

Analogous to Example 45, the following compounds are obtained:

4 '- [[2-ethyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazole

5-yl) -biphenyl

4 '- [[2-n-butyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl-2- (1H-tetrazole)

5-yl) -biphenyl

4 '- [[2-n-propyl-4-methyl-6- (1-xexyl-benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] 2- (1H-tetrazol-5-yl) - biphenyl

4 '- [[2-n-propyl-4-methyl-6- (1-cyclopropyl-benzimidazol-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl) - biphenyl

4 '- [[2-n-propyl-4-methyl-6- (1-cyclohexyl-benzimidazol-2-yl) -benzimidazol-1-yl] methyl] -2- (1H-tetrazol-5-yl) - biphenyl

EXAMPLE 46

4 '- [[2-n-propyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl2-carboxylic acid

Prepare analogously to Example 1 from 4 '- [[2-n-propyl-4-methyl] -6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid in methylene chloride.

Yield: 43% of theory.

M.p .: 239-242 ° C

0 ^^ 0, (500.61) calc .: 0 76.78 H 5.64 N 11.19 found: 76.55 5.60 11.41

The following compounds are obtained analogously to Example 46:

4 '- [[2-ethyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-butyl-4-methyl-6- (benzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-n-hexyl-benzimidazol-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-cyclopropyl-benzimidazol-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

4 '- [[2-n-propyl-4-methyl-6- (1-cyclohexyl-benzimidazol-2-yl) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

EXAMPLE 47

4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-ylmethyl] -2- (1H-tetrazol-5-yl) - biphenyl

Prepared from 4 '- [[2-n-butyl-7- [3- (imidazol-1-yl) -propyloxy] -4-methyl-benzimidazol-1-yl] -methyl] -2- (1-triphenylmethyltetrazole- 5-yl) -biphenyl by cleavage of 1-triphenylmethane group with ethanol / hydrochloric acid.

Yield: 89.8% of theory.

M.p .: 83-87 ° C

C ^ H ^ NgO x 1.5 H ₂ O (573.69) Calc .: C 66.99 H 6.50 N 19.53 Found: 66.83 6.52 19.43

EXAMPLE 48

4 '- [[6- (N-Benzosulfonyl-methylamino) -2-n-butyl-4-methyl-benzimidazol-1-yl] -methylbiphenyl-2-carboxylic acid

Prepare analogously to Example 1 from 4 '- [[6- (N-benzosulfonylmethylamino) -2-n-butyl-4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and of trifluoroacetic acid in methylene chloride.

I

Yield: 95.6% of theory.

M.p .: 211-212 ° C

C ₃₃ H ₃₃ N ₃ O ₄ S (567.70) calcd .: C 69.80 H 5.86 found: 69.52 5.92

N 7.40 S 5.65 7.33 5.84

EXAMPLE 49

4 '- [[6- (N-Benzosulfonyl-n-pentylamino) -2-n-butyl-4-methylbenzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[6- (N-benzosulfonyl-n-pentylamino) -2-n-butyl-4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2- tert-butyl ester carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 81.8% of theory.

M.p .: 232-233 ° C

C ₃₇ H ₄₁ N ₃ O ₄ S (623.81) calculated: C 71.24 H 6.62 N 6.74 S 5.14 found: 71.30 6.77 6.68 5.33

EXAMPLE 50

4 '- [[2-n-butyl-6- (isopropylcarbonylamino) -4-methyl-benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-butyl-6- (isopropyl carbonylamino) -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid acids in methylene chloride.

Yield: 86.3% of theory.

Mp .: 313-315 ° C ^C 3oH ₃₃ N ₃ 0 ₃ (483.61) Calc'd: C 74.51 H 6.88 N 8.69 Found: 74.37 7.10 8.74

EXAMPLE 51

4 '- [[2-n-Butyl-6- (2,3-dimethylmaleinimino) -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid semihydrate

Prepare analogously to Example 1 from ter.butyl ester

4 '- [[2-n-butyl-6- (2,3-dimethylmaleinimino) -4-methyl-benz-imidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 88.9% of theory.

M.p .: 321-322 ° C

C ₃₂ H ₃₁ N ₃ O ₄ x 0.5 H ₂ O (530.62) Calc .: C 72.43 H 6.08 N 7.92 Found: 72.89 6.16 7.89

EXAMPLE 52

4 '- [[6- (2,3-Dimethylmaleinimino) -2-n-propyl-4-methylbenzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid semihydrate

Prepared in analogy to Example 1 from 4 '- [[6- (2,3-dimethylmaleinimino) -2-n-propyl-4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxyl tert-butyl ester acids and trifluoroacetic acids in methylene chloride.

Yield: 75.4% of theory.

M.p .: 329-331 ° C

C ₃₁ H2 ₉ N ₃ O ₄ x 0.5 Hp (516.60) calcd .: C 72.08 H 5.85 N 8.13 found: 72.04 5.84 7.96

EXAMPLE 53

4 '- [(6-acetamino.2-n-butyl-4-methyl-benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid trifluoroacetate semihydrate

Prepare in analogy to Example 1 from 4 '- [(6-acetamino-2-n-butyl4-methyl-benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid in methylene chloride.

Yield: 95.7% of theory.

Melting point: 112-114 ° C (amorphous)

C _2g H ₂₉ N ₃ O ₃ x CF ₃ COOH x 0.5 H ₂ O (578.59) calc .: C 62.28 H 5.40 N 7.26 found: 62.57 5.46 7, 21

EXAMPLE 54

4 '- [[2-n-butyl-4-methyl-6- (morpholinocarbonylamino) -benzimidazol-1-yl] methyl] -biphenyl-2-carboxylic acid

Prepared analogously to Example 1 from 4 '- [[2-n-butyl-4-methyl-6 (morpholinocarbonylamino) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester in trifluoroacetic acid in methylene chloride.

Profit. 80.9% of theor.

Mp .: 279-281 ° C (526.64) Calc .: C 70.70 H 6.51 N 10.64 Found: 70.48 6.50 10.51

EXAMPLE 55

4 '- [[2-n-Butyl-6- (cyclohexylaminocarbonylamino) -4-methylbenzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid semitrifluoroacetate

Prepared analogously to Example 1 from 4 '- [[2-n-butyl-6- (cyclohexylaminocarbonylamino) -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid in methylene chloride.

Yield: 76.9% of theory.

M.p .: 288-289 ° C

0.5 CF ₃ COOH (595.70) Calc .: C 68.55 H 6.51 N 9.41 Found: 69.08 7.02 9.65

EXAMPLE 56

4 '- [[2-n-propyl-4-isopropyl-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl] ethyl] -2- (1H-tetrazol-5-yl ) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-n-propyl-4-isopropyl-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl] -methyl] -2-cyano- of biphenyl and sodium azide in dimetiformamide.

Yield: 14% theory.

M.p .: amorphous

C ₃₅ H _b N _? O (567.71) calcd .: C 74.05 H 5.86 N 17.27 found: 73.97 5.82 17.26 mass spectrum: M ⁺ = 567

EXAMPLE 57

4 '- [[2-n-propyl-5- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-flu-propyl-5- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -biphenyl tert-butyl ester2 -carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 32% of theory.

M.p .: 250-253 ° C

Ο ₃₁ Η * Ν ₄ Ο ₂ (486.60) calculated: C 76.52 H 5.39 N 11.52 found: 76.28 5.47 11.27

EXAMPLE 58

4 '- [[2-n-propyl-4-ethyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-n-propyl-4-ethyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic tert-butyl ester acids and trifluoroacetic acids in methylene chloride.

Yield: 64% of theory.

M.p .: 217-219 ° C

0 ^, 1 ^ 0, (528.70) calc .: 077.24 H 6.10 N 10.60 found: 77.12 6.09 10.75

EXAMPLE 59

4′- [[2-n-propyl-4-ethyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare in analogy as in Example 10 from

4 '- [[2-n-propyl-4-ethyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -2-cyanobiphenyl and sodium azide in dimethylformamide.

Yield: 15% of theory.

M.p .: 215-217 ° C

0 ^, ^ (552.70) Calc .: 0 73.89 H 5.84 N 20.28 Found: 73.66 6.02 20.56

EXAMPLE 60

4 '- [[2-cyclopropyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [[2-cyclopropyl-4-methyl6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid tert-butyl ester and of trifluoroacetic acid in methylene chloride.

Yield: 52% of theory.

M.p .: 244-246 ° C

C ₃₃ H 2 N ₄ O, (512.60) calcd: 077.32 H 5.51 N 10.93 found: 77.75 5.71 10.94

EXAMPLE 61

4 '- [[2-cyclopropyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [[2-cyclopropyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 59% of theory.

M.p .: 245-247 ° C

C ^ Ng (536.65) calc .: C 73.86 H 5.26 N 20.88 found: 73.95 5.42 20.90

Example 62

4 '- [(2-cyclobutyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-cyclobutyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid and trifluoroacetic acid acids in methylene chloride.

Yield: 63% of theory.

Mp .: 189-191 ° C (526.60) calcd .: C 77.55 H 5.74 N 10.64 Found: 77.35 5.92 10.40

Example 63

4 '- [(2-cyclobutyl-4-methyl-6- (1-methylbenz-imidazol-2-yl) benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [(2-cyclobutyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 61% of theory.

M.p .: 197-199 ° C

C ^ N, (550.70) Calc .: C 74.16 H 5.49 N 20.35 Found: 74.12 5.74 20.67

Example 64

4 '- [(2-n-propyl-4-methyl-6- (1-methyl-5-fluoro-benzimidazol-2-yl) benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [(2-propyl-4-methyl-6- (1-methyl-5-fluoro-benzimidazol-2-yl) -benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride. Yield: 34% of theory.

M.p .: 250-252 ° C

C ^ FN.O, (532.60) calcd .: C 74.42 H 5.49 N 10.52 found: 74.14 5.64 10.54

Analogous to Example 64, the following compounds are obtained:

4 '- [(2-n-propyl-4-methyl-6- (pyridin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (quinolin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (isoquinolin-3-yl) -benzimidazol-1-yl) -methyl] -biphenyl2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (isoquinolin-1-yl) -benzimidazol-1-yl) -methyl] -biphenyl2-carboxylic acid

Example 65

4 '- [(2-n-propyl-4-methyl-6- (imidazol [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl) methyl] -2- (1H-tetrazol-5 -yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl6- (imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl) -methyl] -2 -cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 16.5% of theory.

Melting point: above 275 ° C (dec.) (543.65) Calc .: C 68.49 H 5.38 N 23.19 Found: 68.25 5.50 23.37

The following compounds are obtained analogously to Example 65:

4 '- [(2-n-propyl-4-methyl-6- (pyridin-2-yl) -benzimidazol-1-yl) -methyl] -2 (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-methyl-6- (quinolin-2-yl) -benzimidazol-1-yl) -methyl] -2 (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-methyl-6- (isoquinolin-3-yl) -benzimidazol-1-yl) -methyl] -2 (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-methyl-6- (isoquinolin-1-yl) -benzimidazol-1-yl) -methyl] -2 (1H-tetrazol-5-yl) -biphenyl

Example 66

4 '- [(2-n-propyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) -benzimide zol-1-yl ) -methyl] biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [(2-n-propyl-4methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) ) -benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 67% of theory.

Melting point: above 240 ° C (sintering) ^C 32 ^H 32 ^N 4 ° 2 (504.64) Calc .: C 76.16 H 6.39 N 11.10 Found: 75.94 6.46 11.20

Analogous to Example 66, the following compounds are obtained:

4 '- [(2-n-butyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) benzimidazol-1-yl) - methyl] biphenyl-2-carboxylic acid

4 '- [(2-ethyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Example 67

4 '- [(2-n-propyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) benzimidazol-1-yl) - methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl-6 (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) - benzimidazol-1-yl) methyl] -2-cyano biphenyl and sodium azide in dimethylformamide.

Yield: 73.5% of theory.

Melting point: above 275 ° C (dec.)

C ₃₂ H ₃₂ N ₈ (528.67) Calc .: C 72.70 H 6.10 N 21.20 Found: 72.40 6.07 21.48

Analogous to Example 67, the following compounds are obtained:

4 '- [(2-n-butyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) benzimidazo-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-ethyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] -pyridin-2-yl) benzimidazol-yl) -methyl] -2 - (1H-Tetrazol-5-yl) -biphenyl

Example 68

4 '- [(2-n-prop3-4-methyl-6- (1-methyl-6-fluoro-benzimidazol-2-yl) benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepare analogously to example i from tert-butyl ester 4 '- [(2-n-propyl-4-methyl-6 (1-methyl-6-fluoro-benzimidazol-2-yl) -benzimidazol-1-yl) -methyl ] -biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 76% of theory.

Wt .: 243-245%:

C ₃₃ H ₂₉ FN ₄ O ₂ (532.60) calcd .: C 74.42 H 5.49 N 10.52 found: 74.74 5.52 10.77

Mass spectrum: m / e = 532

Example 69

4 '- [(2-n-propyl-4-chloro-6- (1-oxo-isoindolin-2-yl) -benzimidazo] 1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl-4-chloro 6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2 tert-butyl ester -carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 7.5% of theory.

Mp .: 209-2KPC

C ^ CIN ^ (536.04)

Mass spectrum: m / e = 535/537

R _f -value: 0.25 (silica gel; methylene chloride / ethanol = 9: 1).

Example 70

4 '- [(2-n-propyl-4-chloro-6- (1-methylbenzimidazol-2-yl) -benzimidazolyl-yl) -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl4-chloro-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxyl tert-butyl ester acids and trifluoroacetic acids in methylene chloride.

Yield: 52.7% of theory.

M.p .: 292-295 ° C

C ₃₂ H2 ₇ CN ₄ O ₂ (535.06)

R _f -value: 0.30 (silica gel; methylene chloride / ethanol = 19: 1) calculated: C 71.90 H 5.08 N 10.45 Cl 6.63 found: 71.29 5.21 10, 40 6.76

Example 71

4 '- [(2-n-propyl-4-chloro-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) methyl] -2- (1H-tetrazol-5-yl) -biphenyl- hydrochloride

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-chloro-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl, and of sodium azide in dimethylformamide.

Yield: 54.8% of theory.

Melting point: above 204 ° C sintering

C ^ H ^ ClNg x HCl (595.55)

R _f -value: 0.20 (silica gel; petroleum ether / ethyl acetate = 1: 1 and 1% glacial acetate) calc .: C 62.55 H 4.71 N 18.85 Cl 11.85 found: 62.34 4 , 97 18.84 11.57

Example 72

4 '- [(2-n-propyl-4-chloro-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl) -methyl] 2- (1H-tetrazol-5-yl) - biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-chloro-6- (1-oxo-isoindolin-2-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl, and of sodium azide in dimethylfor mamide.

Yield: 24.6% of theory.

M.p .: 246-248 ° C

C ₃₂ H 2 ClN ₇ O (560.08)

R _f -value: 0.15 (silica gel; methylene chloride / ethanol = 9: 1) calculated: C 69.00 H 4.67 N 17.55 Cl 6.40 found: 68.26 4.75 17, 73 6.97

Analogous to Example 72, the following compounds are obtained:

4 '- [(2-n-propyl-4-methyl-6- (4-methyl-imidazol-2-yl) -benzimidazolyl-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-chloro-6- (4,5,6,7-tetrahydro-benzimidazol-2-yl) -benzimidazol-1-yl) methyl] -2- (1H-tetrazole -5-yl) -biphenyl

Example 73

4 '- [(2-n-propyl-4-chloro-6- (cyclohexylaminocarbonylamino) -benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl4-chloro-6- (cyclohexylaminocarbonylamino) -benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid in methylene chloride.

Yield: 75% of theory.

M.p .: 222-224 ° C

C ₃₁ H3 ₃ C1N ₄ O ₃ (545.09)

R _f -value: 0.15 (silica gel; methylene chloride / ethanol = 19: 1) calculated: C 68.50 H 6.10 N 10.30 Cl 6.48 found: 68.89 5.98 10, 02 7.04

Example 74

4 '- [(2-n-Propyl-4-methyl-6-amidino-benzimidazol-1-yl) -methyl] biphenyl 2-carboxylic acid hydrate

a) 4 '- [(2-n-propyl-4-methyl-6-amidino-benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid methyl ester

2.1 g (5 mmol) of 4 '- [(2-n-propyl-4-methyl-6-cyano-benzimidazol-1-yl) -methyl] biphenyl-2-carboxylic acid methyl ester was dissolved in 250 ml of methanol at room temperature. temperature at stirring. Hydrogen chloride was added at 10-20 ° C for 3 hours under ice-cooling. The mixture was then stirred for a further 3 hours at room temperature. The solvent was distilled off in vacuo, the residue was mixed twice with ether and evaporated. The resulting iminoether was taken up in 250 ml of methanol and 10.0 g of ammonium carbonate was added. The reaction mixture was stirred for 12 hours at room temperature. After removal of the solvent in vacuo, the residue is purified over a quartz gel column (grain size 0.063-0.032 mm), using as a elution agent a mixture of methylene chloride and methanol with increasing polarity (9: 1 and 8: 2). The uniform fractions were evaporated in vacuo.

Yield: 1.5 g (58% of theory)

R _f -value: 0.15 (silica gel; eluent: methylene chloride / methanol = 9: 1).

b) 4 '- [(2-n-propyl] -4-methyl-6-amidino-benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

0.51 g (1.0 mmol) of 4 '- [(2-n-propyl-4-methyl-6-amidino-benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid methyl ester was dissolved in 6 ml. tetrahydrofuran, 2.8 ml of a 1.4 M aqueous solution of lithium hydroxide and 3 ml of water are added and stirred for 2 days at room temperature. A solution of 300 mg of ammonium chloride in 4 ml of water is then added. The mixture was stirred for 5 minutes and the resulting precipitate was filtered off with suction, washed with acetone and dried over potassium hydroxide.

Yield: 0.25 g (59% of theory)

Mp: 270-271 ° C (dec.) ^C A ^N 4 ° 2 ^xH 2 ^O (426.53) calcd: C 70.25 H 6.35 N 12.60 found: 70.04 6.23 12 , 50

R _f -value: 0.55 (silica gel; eluting agent: methylene chloride / methanol / ammonia = 2: 1: 0.25).

Analogous to Example 74, the following compounds are obtained:

4 '- [(2-n-propyl-4-methyl-6- (3-methyl-imidazol-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid

4 '- {(2-n-propyl-4-chloro-6- (4,5,6,7-tetrahydro-benzimidazol-2-yl) -benzimidazol-1-yl) methyl] -biphenyl-2-carboxylic acid .

Example 75

4 '- ((2-n-propyl-4-methyl-6- (1-methyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

a) 3-methyl-4-butyrylamino-5-nitro-acetophenone

32.6 g (148 mmol) of 3-methyl-4-butyrylamino-acetophenone were added portionwise at -15 ° C in 300 ml of fuming nitric acid and stirred for a further 30 minutes at -15 ° C. The reaction mixture was then poured onto 3 L of ice with stirring, the crude product was filtered off with suction, washed with 400 ml of water, dried and purified by recrystallization from ethanol / diethyl ether (1: 1).

Yield: 23.8 g (61.0% of theory)

R _f -value: 0.32 (silica gel; methylene chloride)

R _f -value: 0.48 (silica gel; methylene chloride / methanol = 50: 1).

b) 3-methyl-4-butyrylamino-5-nitro-1-bromoacetophenone

To a solution of 23.8 g (90 mmol) of 3-methyl-4-butyrylamino-5-nitro-acetophenone in 900 ml of dichloromethane at room temperature was added dropwise a stirring solution of 16.0 g (200 mmol) of bromine in 140 ml of dioxane, to give a constant complete discoloration of the reaction mixture. The mixture was then stirred for a further 2 hours, then the reaction mixture was evaporated to dryness in vacuo, and the resulting residue was triturated with about 20 ml of dichloromethane / diethyl ether (1: 1), filtered off with suction and dried. This gives 23 g (74% of theory) of 3-methyl-4-butyrylamino-5-nitro- (o-bromo-acetophenone containing about 10% starting material. The product is further digested without further purification.

R _f -value: 0.69 (silica gel; methylene chloride / methanol = 50: 1)

R _f -value: 0.84 (silica gel; methylene chloride / methanol = 9: 1).

c) 2-Butyrylamino-3-nitro-5- (imidazo-4-yl) -toluene

A solution of 6.8 g (20 mmol) of 3-methyl-4-butyrylamino-5-nitro-bromoacetophenone in 20 ml of formamide was heated at 140 ° C for 2 hours. The cooled solution was then poured into about 50 ml of 1 N ammonia and stirred for 15 minutes. The precipitated crude product is filtered off with suction, washed with about 50 ml of water and dried. This gives 4.4 g (75% of theory) of the product which is further digested without further purification.

R _f -value: 0.29 (silica gel; methylene chloride / methanol = 9: 1)

d) 2-Butyrylamino-3-nitro-5- (1-methyl-imidazol-4-yl) toluene

To a solution of 2.5 g (8.7 mmol) of 2-butyrylamino-3-nitro-5- (imidazol-4-yl) -toluene and 5.2 g (30 mmol) of potassium carbonate dihydrate in 30 ml of dimethylsulfoxide are added dropwise 1, 3 g (9.5 mmol) of methyl iodide at room temperature and then stirred for 2 hours. The reaction mixture was then stirred in about 150 ml of water and then extracted four times with 25 ml of ethyl acetate each. The organic extracts are washed with about 30 ml of water, dried and evaporated. The crude product thus obtained was purified by column chromatography (300 g silica gel, eluting agent: methylene chloride / methanol = 30: 1).

Yield: 640 mg (24% of theory)

R _f -value: 0.54 (silica gel; methylene chloride / methanol = 9: 1)

e) 2-Butyrylamino-3-amino-5- (1-methyl-imidazol-4-yl) -toluene

640 mg (2.1 mmol) of 2-butyrylamino-3-nitro-5- (1-methyl-imidazol-4-yl) -toluene was hydrogenated in 30 ml of methanol after the addition of about 200 mg of palladium / charcoal (20%) at room temperature and hydrogen pressure 5 bar. After complete uptake of hydrogen, it is filtered off from the catalyst and the filtrate is evaporated. The crude product thus obtained is further digested without further purification.

Yield: 600 mg (100% theory)

R _f -value: 0.23 (silica gel; methylene chloride / methanol = 9: 1)

f) 2-n-propyl-4-methyl-6- (1-methyl-imidazol-4-yl) -benzimidazole

600 mg (2.1 mmol) of 2-butyrylamino-3-amino-5- (1-methyl-imidazol-4-yl)-toluene was heated in 10 ml of ice for 1 hour at reflux. It was then evaporated to dryness in vacuo, the residue was mixed with about 15 ml of water, adjusted with ammonia to alkaline and extracted four times with about 10 ml of ethyl acetate each. The organic extracts were washed with about 15 ml of water, dried and then evaporated. The crude product thus obtained is further digested without further purification.

Yield: 420 mg (79% of theory)

R _f -value: 0.37 (silica gel; methylene chloride / methanol = 9: 1)

g) tert-butyl ^4> - [(2-n-propyl-4-methyl-6- (l-methyl-imidazol-4-yl) benzimidazol-l-yl) -metill-biphenyl-2-carboxylic acid

To a solution of 200 mg (0.79 mmol) of 2-n-propyl-4-methyl-6- (1-methylimidazol4-yl) -benzimidazole and 90 mg (0.8 mmol) of potassium ter.butylate in 5 ml of dimethylsulfoxide were added 280 mg (0.8 mmol) of 4'-bromomethyl-biphenyl-2-carboxylic acid tert-butyl ester and the mixture was stirred for 90 minutes at room temperature, then stirred in about 40 ml of water, extracted four times with about 10 ml of ethyl acetate each, then the organic extracts rinse with 10 ml of water each, dry and evaporate to dryness. The crude product thus obtained was purified by column chromatography (100 g silica gel, eluent; dichloromethane / methanol = 30: 1).

Yield: 230 mg (56% of theory)

R _f -value: 0.61 (silica gel; methylene chloride / methanol = 9: 1)

h) 4 ^, - [(2-n-propyl-4-methyl-6- (1-methyl-imidazol-4-yl) benzimidazol-1-yl) -methyl-biphenyl-2-carboxylic acid

A solution of 230 mg (0.44 mmol) tert-butyl ester 4 '- [(2-n-propyl-4-methyl-6 (1-methyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] - biphenyl-2-carboxylic acid and 2 ml of trifluoroacetic acid in 10 ml of dichloromethane were stirred at room temperature overnight and then evaporated to dryness. The residue is dissolved in about 5 ml of dilute sodium hydroxide, the solution is neutralized with acetic acid, the precipitate is then filtered off with suction, washed with water and dried.

Yield: 120 mg (59% of theory)

M.p .: 293-295 ° C

R _f -value: 0.39 (silica gel; methylene chloride / methanol = 9: 1).

Analogous to Example 77, the following compounds are obtained:

4 '- [(2-n-propyl-4-methyl-6- (1-ethyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (1-n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (lisopropyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (1-cyclohexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Example 76

4 '- [(2-n-propyl-4-methyl-6- (1-methyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-propyl-4-methyl-6- (1-methyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl, and of sodium azide in dimethylformamide.

Yield: 24% theory.

M.p .: 255-257 ° C

R _f -value 0.24 (silica gel; methylene chloride / methanol = 9: 1)

C ^ N ^ O (506.62) calcd .: C 68.75 H 5.97 N 22.12 found: 68.90 5.97 22.03

Analogous to Example 76, the following compounds are obtained:

4 '- [(2-n-propyl-4-methyl-6- (1-ethyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-methyl-6- (1-n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl-biphenyl-2-carboxylic acid

4 '- [(2-n-propyl-4-methyl-6- (1-isopropyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

4 '- [(2-n-propyl-4-methyl-6- (1-cyclohexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl ) -biphenyl

Example 77

4 '- [(2-ethyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2yl) -benzinididazol-1-yl) -methyl] -2- ( 1H-tetrazol-5-yl) -biphenyl

Prepared in analogy to Example 10 from 4 '- [(2-ethyl-4-methyl-6- (5,6,7,8tetrahydro-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1- yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 21% of theory.

M.p .: amorphous

R _f -value 0.27 (silica gel; methylene chloride / methanol = 9: 1) (514.64) calculated: C 72.35 H 5.88 N 21.78 found: 72.01 5.82 21, 44

Example 78

4 '- [(2-n-propyl-4-methyl-6- (8-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2 -carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl-4-methyl-6- (8-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1- yl-methyl] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 87% of theory.

M.p .: 295-297 ° C

R _f -value 0.34 (silica gel; methylene chloride / methanol = 9: 1) χ Η, Ο (532,65) calculated: C 74.41 H 6.06 N 10.52 found: 74.81 6 , 05 10.43

Example 79

4 '- [(2-n-propyl-4-methyl-6- (2-pyridyl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl4-methyl-6- (2-pyridyl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 56% of theory.

Melting point: above 136 ° C (dec.) X 0.5 H, O (494.60) calculated: C 72.85 H 5.71 N 19.83 found: 72.45 6.01 19.83

Example 80

4 '- [(2-n-propyl-4-methyl-6- (8-methyl-imidazo [1,2-a] pyridin-2-yl)

-benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl-6 (8-methyl-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl) - methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide. Yield: 19% of theory.

M.p .: amorphous

R _{f -} value 0.36 (quartz gel; methylene chloride / ethanol = 9: 1) 0 ^ 1 / ^ / 538,61)

Mass spectrum: m / e = 538

Example 81

4 '- [(2-ethyl-4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepare analogously to Example 1 from tert-butyl ester 4 '- [(2-ethyl4-methyl-6- (5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2-yl) -benzimidazole -1-yl) -methyl] biphenyl-2-carboxylic acid and trifluoroacetic acid in methylene chloride.

Yield: 50% theory.

Melting point:> 300 ° C

R _f -value: 0.16 (silica gel; methylene chlorides / ethanol = 9: 1)

Example 82

4 '- [(2-n-propyl-4-methyl-6- (1-isopropyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenes

1-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl4-methyl-6- (1-isopropyl-imidazol-4-yl) -benzimidazol-1-yl) methyl] -biphenyl-2- tert-butyl ester carboxylic acids and trifluoroacetic acids in methylene chloride.

Yield: 84% of theory.

M.p .: 285-286 ° C

R _f -value: 0.55 (silica gel; methylene chloride / methanol = 9: 1

Example 83

4 '- [(2-n-propyl-4-methyl-6- (1-isopropyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1

H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl-6 (1-isopropyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2-cyano-biphenyl and sodium azide in dimethylformamide.

Yield: 18% of theory.

M.p .: amorphous

R _f -value 0.29 (silica gel; methylene chloride / methanol = 9: 1)

C ₃₁ H ₃₂ N ₈ (516.66)

Mass spectrum: m / e = 516

Example 84

4 '- [(2-n-propyl-4-methyl-6' (1-n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl4-methyl-6- (1n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) methyl] -biphenyl and trifluoroacetic acid tert-butyl ester in methylene chloride.

Example 85

4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid

Prepared in analogy to Example 1 from 4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] biphenyl tert-butyl ester, and of trifluoroacetic acid in methylene chloride.

Example 86

4 '- [(2-n-propyl-4-methyl-6- (1n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepare analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl-6 (1n-hexyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] 2-cyano-biphenyl and of sodium azide in dimethylformamide.

Example 87

4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -ethyl] -2- (1H-tetrazol-5-yl) -biphenyl

Prepared analogously to Example 10 from 4 '- [(2-n-propyl-4-methyl-6- (1-benzyl-imidazol-4-yl) -benzimidazol-1-yl) -methyl] -2-cyanobiphenyl, and of sodium azide in dimethylformamide.

For the following pharmaceutical applications, any administered compound of formula I, in particular those in which R ₄ represents a carboxy or 1H-tetrazolyl group, can be used as an effective substance:

Example I

Ampoules containing 50 mg of active substance per 5 ml of active substance mg

ΚΗ, ΡΟ,

At ₂ HPO ₄ x2H ₂ O

NaCl water for injection mg 50 mg 12 mg 5 ml

Preparation:

Dissolve the buffered substances and isotonic agent in one part of the water. The active ingredient is added and after complete dissolution is filled with water to nominal volume.

Example II

Ampoules containing 100 mg of active ingredient per 5 ml of active ingredient 100 mg of methylglucamine 35 mg of glycofurol 1000 mg of block polymer polyethylene glycolapolipropylene glycol 250 mg of water for injection 5 ml

Preparation:

Methylglucamine is dissolved in one part of the water and the active substance is introduced into the solution while stirring and heating. After addition of the solvent, fill with water to nominal volume.

Example III

Tablets containing 50 mg active ingredient 50.0 mg calcium phosphate 70.0 mg milk sugar 40.0 mg corn starch polyvinylpyrrolidone magnesium stearate

35,0 mg

3.5 mg

1.5 mg

200.0 mg

Preparation:

The active substance, CaHPO ₄ . milk sugar and cornstarch are moistened evenly with PVP aqueous solution. Sift the mass through a 2 mm sieve, dry at 50 ° C in an air-conditioned oven and sift again.

After the lubricant is mixed, the granulate is compressed on a tablet machine.

Example IV

Dragees containing 50 mg active ingredient 50.0 mg lysine 25.0 mg milk sugar 60.0 mg corn starch 34.0 mg gelatin 10.0 mg magnesium stearate 1.0 mg

180,0 mg

Preparation:

The active substance is mixed with excipients and moistened with an aqueous gelatin solution. After sieving and drying, the granulate is mixed with magnesium stearate and compressed into cores.

The prepared cores are coated according to known coating processes. A dye is added to the suspension or solution for more expensive.

Example V

Dragees containing 100 mg of active ingredient lysine milk sugar cornstarch polyvinylpyrrolidone microcrystalline cellulose magnesium stearate

100.0 mg 50.0 mg 86.0 mg 50.0 mg 2.8 mg 60.0 mg 1.2 mg

350,0 mg

Preparation:

The active substance is mixed with excipients and moistened with an aqueous solution of PVP. The wet mass is sieved through a 1.5 mm sieve and dried at 45 ° C. After drying, the magnesium stearate is again sieved and mixed. Compress this mixture into cores.

The prepared cores are coated according to the known coating process. Dyes may be added to the suspension or solution for dragees.

Example VI

Capsules containing 250 mg active ingredient 250.0 mg corn starch 68.5 mg magnesium stearate 1.5 mg

320,0 mg

Preparation:

The active substance and cornstarch are mixed and moistened with water. The wet mass is sieved and dried. The dry granulate is sieved and mixed with magnesium stearate. The final mixture is filled into size 1 hard gelatin capsules.

Example VII

Oral suspensions containing 50 mg of active ingredient per 5 ml of active ingredient 50.0 mg of hydroxyethylcellulose 50.0 mg of sorbic acid 5.0 mg of sorbit 70% 600.0 mg of glycerin 200.0 mg of flavoring 15.0 mg of water ad 5.0 ml

Preparation:

The distilled water is heated to 70 ° C. Hydroxyethylcellulose is dissolved therein by stirring. After addition of the sorbite and glycerin solution, cool to room temperature. At room temperature, sorbic acid, aroma and active ingredient are added. To vent the suspension, evacuate the suspension with stirring. The dose = 50 mg is contained in 5.0 ml.

Example VIII

Suppositories containing 100 mg active substance active fat

100.0 mg 1600.0 mg

1700,0 mg

Preparation:

Melt the solid fat. At 40 ° C, the ground active substance was homogeneously dispersed into the melt. Cool to 38 ° C and pour into slightly pre-cooled suppository forms.

Claims (10)

PATENT APPLICATIONS 1. Benzimidazoles of the general formula in which they are understood Rj in position 4 is a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms, a cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group, and R 3 is an alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted with an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms which is in position 2, 3, 4 or 5 substituted with a benzimidazolyl group, or tetrahydrobenzimidazolyl group or even if R ₄ represents a 1H-tetrazolyl group, 2- (imidazol-1-yl) -ethoxy group, alkylsulfonyloxy group having 1 to 4 carbon atoms, benzenesulfonyloxy or phenylalkane sulfonyloxy group, optionally on a nitrogen atom with alkyl a group of 1 to 6 carbon atoms with a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group substituted acylamino group in which the acyl residue represents an alkanoyl group of 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group having from 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, said phenyl nucleus may in each case be mono- or disubstituted by a fluorine, chlorine or bromine atom, with a methyl or methoxy group, and the substituents may be the same or different, phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, wherein the phthino is a carbonyl group the group substituted by a methylene, allrylmethylene or dialkylmethylene group, as well as the methylene group in the homophthalimino group may be substituted by one or two alkyl groups and the abovementioned phenyl cores are mono- or disubstituted by alkyl or alkoxy groups, the same being substituents ah different and may at the same time be completely ah 'partially hydrated, optionally with one or two alkyl groups ah with a tetramethylene or pentamethylene group substituted 5-, 6- ah 7-membered alkyleneimine or alkenyleneimine group in which the methylene group may be substituted by carbonyl or a sulfonyl group, an imino group bicycloalkane-2,3-dicarboxylic acids ah imino group bicycloalkene2,3-dicarboxylic acids in which the bicycloalkane and bicycloalkenes each contain 9 or 10 carbon atoms may be substituted by 1, 2 or 3 methyl groups and the endomethylene group may be replaced by an oxygen atom , optionally, with one or two alkyl groups each having 1 to 6 carbon atoms, a substituted amidine group, a glutaric acid imine group in which the n-propylene group is perfluorinated, which may be substituted with one or two alkyl groups or tetramethylene, or a pentamethylene group, optionally an alkyl or phenyl group, a mono- or disubstituted maleic acid imido group, wherein the substituents may be the same or different, a 5-membered heteroaromatic ring containing an imine group via an imino group, an oxygen atom or sulfur or imino group and oxygen, sulfur or nitrogen atom, or bonded via a carbon atom A 6-membered heteroaromatic ring containing 1 or 2 nitrogen atoms, wherein said heteroaromatic rings in the carbon framework may be substituted by an alkyl group of 1 to 6 carbon atoms or a phenylalkyl group and bonded to the 6-membered heteroaromatic rings each time 100 through two adjacent carbon atoms of a n-propylene or n-butylene group or bonded to both 5-membered and 6-membered heteroaromatic rings each time via two adjacent carbon atoms, n-propylene, n-butylene or 1,3-butadienyl group or via the imino group and the adjacent carbon atom of the n-butylene or 1,3butadienyl group and in the thus formed annelated pyridine ring the methine group with the nitrogen atom and the vinylene group in position 3, 4 can be substituted for the nitrogen atom of the resulting pyridine ring, with the sulfur atom or in the resulting annelated phenyl ring, one or two methine groups may be replaced by nitrogen atoms, wherein the aforementioned condensed aromatic or heteroaromatic rings in the carbon framework may be monosubstituted by a fluorine, chlorine or bromine atom, alkyl, alkoxy, hydroxy phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or diaUrylaminosulfonyl group or disubstituted by a fluorine or chlorine atom, by methyl, methoxy or hydroxy groups, such as substituents as well as substituents such as with a methylene or ethylene bridge to one another, and optionally in the imidazole ring, the NH group present may be substituted by an alkyl group of 1 to 6 carbon atoms, a phenylalkyl group or a cycoloalkyl group, or a pyrrolidine, piperidine or pyridine ring bonded through the carbon atom wherein a phenyl residue is condensed on the pyridine ring via two adjacent carbon atoms and is a methylene group which may be substituted by a carbonyl group, optionally alkyl, phenylalkyl, tetramethylene, pentamethylene, pentamethylene, or methyl adjacent to the pyrrolidine or piperidine ring a substituted imidazolidinedione group, a pyridazin-3-one or a dihydro-pyridazin-3-one group, which may be substituted in position 2 by, optionally, a phenyl group of substituents: 'Wine group, and additionally in a carbon framework of 1 or 2 alkyl groups, R ₇ -NR ₆ -CO-NR ₅ -group in which they represent R _{5 is} a hydrogen atom, an alkyl group of 1 to 8 carbon atoms, a cycloalkyl group of s 101 5 to 7 carbon atoms or a phenylalkyl group, R _{6 is} a hydrogen atom, an alkyl group of 1 to 8 carbon atoms, an alkenyl group of 3 to 5 carbon atoms, a phenyl group, a phenylalkyl group or a cycloalkyl group of 5 to 7 carbon atoms, R _? a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, or one of the radicals R _$, R ₆ or _R? also a bicyclohexyl or biphenylyl group or R ₆ and R _? together with a nitrogen atom lying between them an alkyleneimine group of 4 to 6 straight carbon atoms or a morpholine group, or R ₅ and R ₆ together are an alkylene group of 2 to 4 carbon atoms, a 1H, 3H-quinazolin-2,4-dione-3-yl- or pentamethylene-oxazolin-2-yl group, or R 1 is a hydrogen atom or in the 5, 6 or 7 position of a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms, a fluoromethyl, difluoromethyl or trifluoromethyl group, and R 2 is a 5-membered heteroaromatic ring containing a imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or a 6-membered heteroaromatic ring containing 1 or 2 through a carbon atom 2 nitrogen atoms, the aforementioned heteroaromatic rings being optionally substituted in the carbon framework by an alkyl group of 1 to 6 carbon atoms or a phenylalkyl group and bonded to the 6-membered heteroaromatic rings each time by two adjacent n-propylene carbon atoms or n -butylene groups, or bonded to both 5-membered and 6-membered heteroaromatic rings, each via two adjacent carbon atoms of the n-propylene, n-butylene or 1,3-butadienyl group, or via the imino group and the adjacent carbon atom of the n-butylene or 1,3-butadienyl group and in the thus formed annelated pyridine ring the methine group is replaced by a nitrogen atom and the vinylene group in position 3,4 to the nitrogen atom of the pyridine ring formed, with the sulfur atom or in the thus formed annelated phenyl ring one or two methine groups are replaced by nitrogen atoms, with the aforementioned aforementioned condensed aromatic or heteroaromatic rings in the carbon framework having a carbon-bearing framework fluorine, chlorine or bromine atom, with alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alklamine, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, fluormethyl, difluoromethylsulfonyl, difluoromethylsulfonyl, alkali a dialkylaminosulfonyl group or may be disubstituted by a fluorine or chlorine atom, by methyl, methoxy or hydroxy groups, as well as the two methyl substituents in position 1,2 may be connected to each other by a methylene or ethylene bridge and optionally in imidazole the ring-present NH group may be substituted by alk an aryl group of 1 to 6 carbon atoms, a phenylalkyl group or a cycloalkyl group, wherein, if (i) R 1 is a hydrogen atom, R _{3 is a} n-propyl group and R _{4 is a} carboxyl group, R _? in position 6 it cannot represent a 3-methyl-imidazo [4,5-b] pyridin-2-yl or 3-n-hexyl-imidazo [4,5-b] pyridin-2-yl group, or if they represent (ii) R _{x is} a hydrogen atom, R _{3 is a} n-propyl or n-butyl group and R _{4 is a} 1H-tetrazolyl group, R 2 in position 5 or 6 cannot represent a benzoxazol-2-yl group or, if (iii) R 1 is a hydrogen atom, R ₃ n-propyl group and R ₄ carboxy group, R ₂ in position 5 or 6 cannot represent l-methylbenzimidazol-2-yl group or in position 6 cannot represent ln-butylbenzimidazol-2-yl, 1,5 dimethylbenzimidazol-2- or 1-methyl-5-trifluoromethylbenzimidazol-2-yl group, or if (iv) R _{x is} a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is a} carboxy or 1H-tetrazolyl group, R ₂ in position 6 cannot represent l -methylbenzimidazol-2-yl group or, if (v) R 1 represents a hydrogen atom, R _{3 a} n-butyl group and R _{4 a} carboxy group, R ₂ in position 6 cannot represent the benzimidazol-2-yl group ah 'beyond the carbon atom pyrrolidine bound, taps a ridin or pyridine ring, wherein 103 a phenyl residue is condensed onto the pyridine ring via two adjacent carbon atoms and the methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring may be replaced by a carbonyl group, R _{3 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms in which the methylene group may be replaced by an oxygen or sulfur atom or a cycloalkyl group of 3 to 5 carbon atoms, and R ₄ carboxy, cyano, 1H-tetrazolyl or 1-triphenylmethyltetrazolyl group, alkoxy carbonyl group having a total of 2 to 5 carbon atoms, alkanesulfonylaminocarbonyl, arylsulfonylaminocarbonyl or trifluonnethanesulfonylaminocarbonyl group, their 1-, 3-iso-organic isomeric mixtures acids or bases, unless otherwise stated above, the alkanoyl, alkyl or alkoxy moiety may each contain 1 to 3 carbon atoms, as well as the aforementioned cycloalkyl moiety may each contain 3 to 7 carbon atoms. Benzimidazoles of the general formula I according to claim 1, wherein R ₁ in position 4 represents a fluorine, chlorine or bromine atom, an alkyl group of 1 to 3 carbon atoms, a cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group, and R _{2 is an} alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted with an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted with benzimidazolyl or a tetrahydrobenzimidazolyl group, optionally a nitrogen atom with an alkyl group of 1 to 5 carbon atoms, substituted acylamino group in which the acyl residue represents an alkanoyl group with 2 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group of 1 to 3 carbon atoms or a benzenesulfonyl group, a phthalimino or homophthalimino group, wherein the carbonyl group in the phthalimino group is replaced by a methylene group as well as the methylene group in the homophthalimino group may be substituted by one or two alkyl groups, 104 optionally substituted by one or two alkyl groups or a tetramethylene or pentamethylene group substituted by a 5-, 6- or 7-membered alkylimino or alkenyleneimine group in which the methylene group may be substituted by a carbonyl or sulfonyl group, a glutamic acid imine group in which the n-propylene group is perfluorinated, which may be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, optionally a alkyl or phenyl group, a mono- or disubstituted imido group of maleic acid, the substituents being the same or different, optionally with one or two alkyl groups of 1 to 4 carbon atoms each substituted amidine group, optionally in position 1 with an allyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, wherein the phenyl core of one of the aforementioned benzimidazole groups may be further substituted by a fluorine atom , methyl or trifluoromethyl group, imidazo [2,1-b] thiazol-6-yl, imidazo [1,2-a] pyridin-2-yl, 5,6,7,8 -tetrahydro-imidazo [1,2-a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] -pyridin-2-yl, imidazo [4,5 -c] pyridin-2-yl, imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl , imidazo [4,5-c] -pyridin-2-yl, purin-8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl, or imidazo A [4,5-d] pyridazin2-yl group linked by a carbon atom to a pyrrolidine, piperidine or pyridine ring, wherein a phenyl residue is condensed to the pyridine ring via two adjacent carbon atoms and is a methylene group adjacent to the nitrogen atom of the pyrrolidine or piperidine ring, optionally substituted by a carbonyl group, optionally in position 1, with an alkyl group of 1 to 3 carbon atoms or a benzyl group substituted with an carbon-bonded imidazolyl group, which may additionally be substituted in the carbon framework by an alkyl group of 1 up to 3 atoms 105 carbon, optionally alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group substituted imidazolidinedione group, pyridazin-3-one or dihydro-pyridazin-3-one group, which in position 2 may be substituted by a methyl or benzyl group , R ₇ -NR ₆ -CO-NR ₅ -group in which they represent R _{5 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, a cyclohexyl or benzyl group, R _{6 is} a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, an allyl, cyclohexyl, benzyl or phenyl group, R _? a hydrogen atom or an alkyl group of 1 to 3 carbon atoms or R ₆ and R _? together with the nitrogen atom lying between them, an alkyleneimine group of 4 to 6 straight carbon atoms or a morpholine group, or R ₅ and R ₆ together are an alkylene group of 2 or 3 carbon atoms, or Rf is a hydrogen atom or in the 5,6 or 7 position of a fluorine, chlorine or bromine atom, an alkyl group of 1 to 4 carbon atoms or a trifluoromethyl group, and R ₂ optionally in position 1 having an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, the phenyl nucleus of one of the aforementioned benzimidazole groups being optionally substituted by a fluorine atom, methyl or trifluoromethyl group imidazo [2, 1b] thiazol-6-yl, imidazo [1,2-a] pyridin-2-yl, 5,6,7,8-tetra-hydro-imidazo [1,2-a] pyridine- 2-yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] pyridin-2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1, 2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-c] pyridin-2 -ily, purine-8-yl, 106 imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl or imidazo [4,5-d] pyridazin-2-yl group, pyrrolidine-linked via a carbon atom, a piperidine or pyridine ring, wherein a phenyl residue is condensed on the pyridine ring via two adjacent carbon atoms and the methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring can be replaced by a carbonyl group, or optionally in position 1 with an alkyl group of 1 to 3 carbon atoms or a benzyl group substituted with an imidazolyl group attached via a carbon atom which may additionally be substituted by an alkyl group of 1 to 3 carbon atoms in the carbon framework, where, if (v) R 1 is a hydrogen atom, R _{3 is a} n- the butyl group and the R ₄ carboxy group, R, in position 6 cannot represent the benzimidazol-2-yl group, R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and R _{4 is a} carboxy or tet-tetrazolyl group, their 1-, 3-isomer mixtures and their salts, with inorganic or organic acids ah bases, unless otherwise stated above the alkanoyl, alkyl or alkoxy moiety may contain at any one time 1 to The 3 carbon atoms as well as the aforementioned cycloalkyl moiety may each contain from 3 to 7 carbon atoms. Benzimidazoles of the general formula I according to claim 1, in which they are Rj in position 4 is a chlorine atom, an alkyl group of 1 to 3 carbon atoms or a trifluoromethyl group, and R, an alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted with an imidazolyl group, an alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted with benzimidazolyl or tetrahydrobenzimidazolyl a group, an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or an N-benzenesulfonylmethylamino group, 107 a phthalimino or homophthalimino group, wherein the carbonyl group in the phthalimino group may be replaced by a methylene group, A 5-, 6- or 7-membered alkylimino group in which the methylene group is replaced by a carbonyl or sulfonyl group, a glutamic acid imine group in which the n-propylene group may be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, optionally with an alkyl or phenyl group a mono- or disubstituted imido group of maleic acid, the substituents may be the same or different, optionally in position 1 with an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazole-2- group, wherein the phenyl core of one of the benzimidazole groups mentioned above may be further substituted by a fluorine atom, a measuring or trifluoromethyl group, imidase [2, 1b] thiazol-6-yl, imidase [1,2-a] pyridin-2 -yl, 5,6,7,8-tetrahydro-imidazo [1,2a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] pyridine 2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-c] -pyridin-2-yl, purin-8-yl, imidazo [4,5-b] pyrazine A 2-yl, imidazo [4,5-c] pyridazin2-yl or imidazo [4,5-d] pyridazin-2-yl group, via a carbon atom, a pyrrolidine, piperidine or pyridine ring is attached, via a pyridine ring via of two adjacent carbon atoms is a fused phenyl residue and the methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring may be replaced by a carbonyl group, in position 1, with an alkyl group of 1 to 3 carbon atoms, or a benzyl group substituted imidazol-4-yl group, which may additionally be substituted in the carbon framework by an alkyl group of 1 to 3 carbon atoms, a pyridazin-3-one or a dihydro-pyridazin-3-one group which may be substituted in the 2-position by 108 methyl or benzyl group, A R 6 -NR 4 -CO-NR 1 -group in which they represent R _{5 is} a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, a cyclohexyl or benzyl group, R _{6 is} a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, an allyl, cyclohexyl, benzyl or phenyl group, R _? a hydrogen atom or an alkyl group of 1 to 3 carbon atoms or R ₆ and R _? together with the nitrogen atom between them an alkylene imine group of 4 to 6 straight carbon atoms or a morpholine group, or R ₅ and R ₆ together are an alkylene group of 2 or 3 carbon atoms, or R 1 is a hydrogen atom or a 5, 6 or 7 alkyl group having 1 to 4 carbon atoms or a trifluoromethyl group, and R 1, optionally, in position 1 with an alkyl group of 1 to 6 carbon atoms or a cycloalkyl group substituted benzimidazol-2-yl group, wherein the phenyl core of one of the aforementioned benzimidazole groups may be further substituted by a fluorine atom, methyl or trifluoromethyl group, imidazo [2, 1b] thiazol-6-yl, imidazo [1,2-a] pyridin-2-yl, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2 -yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [4,5-b] pyridin-2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [1, 2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl, imidazo [4,5-c] -pyridin-2 -yl, purin-8-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl or imidazo [4,5-d] pyridazin-2-yl group, a pyrrolidine, piperidine or pyridine ring attached to the carbon atom, wherein a phenyl residue is condensed to the pyridine ring via two adjacent carbon atoms and the methylene group is adjacent to the nitrogen atom in the pyrrolidine or piperidine ring u can be replaced with a carbonyl group or in position. 1 with an alkyl group of 1 to 3 carbon atoms or with benzyl 109 group substituted imidazol-4-yl group which may be further substituted in the carbon framework by an alkyl group of 1 to 3 carbon atoms, where, if (v) R 1 represents a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is} carboxy the group R ₂ in position 6 cannot represent the benzimidazol-2-yl group, R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and R ₄ carboxy or 1H-tetrazolyl group, their 1-, 3-isomer mixtures and their salts with inorganic or organic acids or bases. Benzimidazoles of the general formula I according to claim 1, wherein R1 in position 4 represents a methyl group or a chlorine atom, and R ₂ alkoxy group of 3 to 5 carbon atoms in position 3, 4 or 5 substituted with imidazolyl group, alkoxy group of 2 to 5 carbon atoms in position 2, 3, 4 or 5 substituted with benzimidazolyl or tetrahydrobenzimidazolyl a group, an alkanoylamino group having 2 to 5 carbon atoms in the alkanoyl moiety or an N-benzenesulfonylmethylamino group, phthalimino or homophthalimino group, the carbonyl group in the phthalimino group being substituted by a methylene group, A 5-, 6- or 7-membered alkyleneimino group in which the methylene group is replaced by a carbonyl or sulfonyl group, optionally an alkyl or phenyl group, a mono- or disubstituted imido group of maleic acid, wherein the substituents may be the same or different, in for example, in the 1-position with an alkyl group of 1 to 3 carbon atoms substituted 110 benzimidazol-2-yl group, wherein the phenyl core of one of the aforementioned benzimidazole groups can be further substituted by a fluorine atom, imidazo [1,2a] pyridin-2-yl, 5,6,7,8-tetrahydro-imidase - [1,2-a] pyridin-2-yl, imidazo [1,2a] pyrimidin-2-yl or imidazo [2, 1b] thiazol-6-yl group, in position 1 with an alkyl group of 1 to 3 atoms carbon substituted imidazol-4-yl group, pyridazin-3-one ah dihydro-pyridazin-3-one group which may be substituted in the 2-position with a methyl or benzyl group, ah Rj is a hydrogen atom or in the position 5,6 ah 7 methyl group and R ^ optionally in position 1 with an alkyl group of 1 to 3 carbon atoms substituted benzimidazol-2-yl group which may be further substituted in the phenyl core by a fluorine atom, in position 1 with an alkyl group of 1 to 3 carbon atoms substituted imidazol-4-yl group ah imidazo [1,2-a] pyridin-2-yl group, where, if (v) R _{3 is} a hydrogen atom, R _{3 is a} n-butyl group and R _{4 is a} carboxy group, R 2 is in position 6 cannot represent the benzimidazol-2-yl group, R _{3 is an} alkyl group of 1 to 5 carbon atoms or a cycloalkyl group of 3 to 5 carbon atoms, and R _{4 is a} carboxy or tet-tetrazolyl group, their 1-, 3-isomer mixtures and their salts, with inorganic or organic acids or bases. 5. The following benzimidazoles of the general formula I according to claim 1: (a) 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, 111 (b) 4 '- [[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl)' benzimidazolyl-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (c) 4 '- [[2-n-propyl-4-methyl-6- (1-oxo-isoindolin-2-yl) -benzimidazolyl-yl] -methyl] -2- (1H-tetrazole- 5-yl) -biphenyl, (d) 4 '- [[2-n-propyl-4-methyl-6- (butansultam-1-yl) -benzimidazolyl-yl] -methyl] -2- (1H-tetrazole- 5-yl) -biphenyl, (e) 4 '- [[2-n-butyl-6- (2,3-iminodimethylammonic acid) -4-methyl-benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid , (f) 4 '- [[2-n-butyl-6- (isopropylcarbonylamino) -4-methyl-benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, (g) 4' - [[2- n-Butyl-4-methyl-6- (morpholinocarbonylamino) -benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, (h) 4 '- [[2-n-butyl-6- (cyclohexylaminocarbonylamino) -4 -methyl-benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, (i) 4 '- [(2-cyclopropyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, (j) 4 '- [(2-n-propyl-4-methyl-6- (1-methyl-5-fluoro-benzimidazol-2-yl) benzyl midazoll-yl] -methyl] -biphenyl-2-carboxylic acid, (k) 4 '- [(2-n-propyl-4-methyl-6- (imidazo [1,2-a] pyrimidin-2-yl) - benzimidazolyl-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (1) 4 '- [(2-n-propyl-4-methyl-6- (4,5,6, 7-Tetrahydro-imidazo- [1,2-a] pyridin-2-yl) -benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid, 112 (m) 4 '- [(2-n-propyl-4-methyl-6- (4,5,6,7-tetrahydro-imidazo [1,2-a] pyridin-2-yl) -benzimidazole- 1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (n) 4 '- [(2-n-propyl-4-chloro-6- (1-methylbenzimidazol-2-yl) ) - Benzimidazolyl-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (o) 4 '- [[2-n-propyl-4-methyl-6- (imidazo [2, 1b] ] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid, (P) 4 '- [[2-ethyl-4-methyl-6- (butansultam-1-yl) -benzimidazole -1-yl] -methyl] 2- (1H-tetrazol-5-yl) -biphenyl, (q) 4 '- [[2-n-butyl-4-methyl-6- (1-methylbenzimidazol-2-yl) ) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (r) 4 '- [[2-n-propyl-6- (imidazo [1,2-a] ] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (s) 4 '- [[2-n-propyl-4-methyl- 6- (imidazo [1,2-a] pyridin-2-yl) -benziniidazolyl-yl] -methyl] -biphenyl-2-carboxylic acid, (t) 4 '- [[2-n-propyl-4-methyl -6- (imidazo [1,2-a] pyridin-2-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (u) 4 '- [[2 -n-propyl-4-methyl-6- (imidazo [2,1-b] thiazol-6-yl) - b enzymidazol-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl and (v) 4 '- [(2-n-propyl-4-methyl-6- (1-methyl-6-fluoro) -benzimidazol-2-yl) benzimidazol-1-yl) -methyl] -biphenyl-2-carboxylic acid, their 1-, 3-isomer mixtures, and their salts with inorganic or organic acids or bases. 113 6. Physiologically tolerable salts of the compounds according to at least one of claims 1 to 5 with inorganic or organic acids or bases. Medicaments comprising a compound according to at least one of claims 1 to 5 or a physiologically tolerated salt according to claim 6 in addition to one or more inert carriers and / or diluents, as appropriate. Use of compounds according to at least one of claims 1 to 6 for the preparation of a medicament with an angiotensin antagonist effect. Method for the preparation of a medicament according to claim 8, characterized in that the compound according to at least one of claims 1 to 6 is incorporated in one or more inert carriers and / or diluents in a non-chemical manner. A process for the preparation of benzimidazoles according to claims 1 to 6, characterized in that a) a compound of the general formula (II) wherein: R 1 and R ₂ as defined in claims 1 to 5, one of the residues Xj or Y represents a group of the general formula 114 and the second of residues X _t or Yj represents a group of the general formula - NH ^ 1 / ^Z 2 C - R, wherein R 2 and R ₄ as defined in claims 1 to 5, R _g represents a hydrogen atom or an R ₃ CO group, as defined Rg angles previously mentioned, Zj and Z ₂ , which may be the same or different, optionally represent substituted amino groups ah optionally with lower alkyl groups substituted hydroxy or mercapto groups, or Zj and Z ₂ together represent an oxygen atom ah sulfur, optionally with an alkyl group of 1 to 3 carbon atoms substituted imino group, an alkyldioxy or alkylenedithio group each 2 ah 3 carbon atoms, wherein one of the radicals X _: or represent a group of the general formula or Z Z V / ² - NH - C - R _{3 is} cyclized and optionally reduced the corresponding N-oxide, or b) benzimidazole of the general formula 115, (111) in which R ₁ to Rg as defined in claims 1 to 5 is reacted with a biphenyl compound of the general formula wherein R ₄ as defined in claims 1 to 5 and Z ₃ represents the nucleophilic exit group, or c) for the preparation of a compound of general formula I in which R ₄ represents a carboxy group, a compound of general formula R ₁ to R ₃ as defined in claims 1 to 5 and R ₄ 'represents a group which can be converted into a carboxy group by hydrolysis, thermolysis or hydrogenolysis, converted to the corresponding carboxy compound or d) for the preparation of a compound of general formula I wherein R ₄ is 1H-tetrazolyl 116 group, the protective residue of a compound of the general formula in which they are R _p and Rg as defined in claims 1 to 5 and R ₄ 'represents, in position 1 or 3, with a protective residue a protected tet-tetrazolyl group, cleaved or e) for the preparation of a compound of general formula I in which R ₄ represents an 1H-tetrazolyl group, a compound of general formula R 1 to R ₃ as defined in claims 1 to 5 is reacted with hydrochloric acid or its salts, or f) for the preparation of compounds of general formula I, in which R ₂ represents one of claims 1 to 5 of the imidazo [1,2-a] pyridin-2-yl, imidase [1,2-a] pyrimidin-2-yl , imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazin-2-yl, imidazo [1,2-b] pyridazin-2-yl or imidazo [2, 1b] thiazole -6-ilno 117 group, the compounds of the general formula (VIII) are metabolised, in which one of the residues A, B, C or D represents a methine group or a nitrogen atom and the rest of the residues A, B, C or D of the methine group or A and B are each a methine group and -C = D-group sulfur atom, R ₉ represents a hydrogen, fluorine, chlorine or bromine atom, alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanesulfonylmethyl, trifluoromethylsulfonyl, alkylsulfonylmethyl, trifluoromethylsulfonylamino a dialkylaminosulfonyl group and R _{10 is} a hydrogen, fluorine or chlorine atom, a methyl, methoxy or hydroxy group, where, when R 1 and R _{10 are} adjacent methyl groups, they may be linked to a methylene or ethylene group by a compound of general the formula they are in 118 R p R ₄ and R ₄ as defined in claims 1 to 5, With a ₄ nucleophilic starting group, such as a halogen atom, e.g. chlorine or bromine atom. g) For the preparation of compounds of general formula I in which R2 represents one of the claims 1 to 5 of said groups: benzimidazol-2-yl, imidase [4,5-b] pyridin-2-yl, imidase [4,5-c ] pyridin-2-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] pyridazin-2-yl, imidazo [4,5-d] pyridazin-2-yl or purine -8-yl group, cyclize a compound of the general formula in which none, one or two of the residues Aj, B _p C _x or D _{3 represent} a nitrogen atom and the remaining residues of the residues Ap B _p C ₃ or D _{1 of the} methine group, R _{n is} a hydrogen, fluorine, chlorine or bromine atom, alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethylsulfonyl, alkynoosulfonyl, alkyloxymethyl, alkali a dialkylaminosulfonyl group and R ₁₂ a hydrogen, fluorine or chlorine atom, a methyl, methoxy or hydroxy group, one of the residues X ₂ or Y ₂ R _{J 3} -NH group and the other of the residues or Y ₂ group of the general formula 119 wherein R & D _3, and R ₄ are as defined in claims 1 to 5, one of the radicals R ₁₃ or R ₁₄ is a hydrogen atom and the other of the radicals R _J3, or R ₁₄ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or cycloalkyl group, Z ₅ and Z ₆ , which may be the same or different, optionally substituted amino groups, or optionally lower alkyl groups substituted hydroxy or mercapto groups, or Z ₅ and Z ₆ together the oxygen or sulfur atom optionally with an alkyne group of 1 to 3 carbon atoms substituted imino group, an alkyldioxy or alkylenedithio group each 2 or 3 carbon atoms, and the corresponding N-oxide thus obtained is reduced and thus the resulting compound is optionally subsequently hydrolyzed or h) For the preparation of compounds of general formula I in which R2 represents a dihydropyridazin-3-one or pyridazin-3-one group which may be substituted in position 2, optionally substituted by a phenyl group, substituted alkyl group of 1 to 3 carbon atoms, or may be substituted on the carbon backbone by one or two alkyl groups of at least 1 to 3 carbon atoms each, the carboxylic acids of the general formula in which are R _p Rg and R ₄ as defined in claims 1 to 5, 120 E, optionally, with one or two alkOn groups of 1 to 3 carbon atoms each, is substituted by an ethylene or ethylene ethylene group, or by its reaction acid derivatives, such as its esters, amides or halides, with hydrazine of the general formula H ₂ N - NHR ₁₅ (XIII) in which R ₁₅ represents a hydrogen atom or, optionally, a phenyl group substituted with an alkyl group of 1 to 3 carbon atoms, and, if necessary, between the reductions a) to h), the protective residue used is cleaved off and / or optionally thereafter 1- , The 3-isomer mixture of the compound of general formula I isomerically separated into its 1- and 3-isomer, or the compound of the general formula I thus obtained converted into its salt, in particular for pharmaceutical use, in its physiologically acceptable salt with inorganic or organic acid, or base.