KR920016431A - Benzimidazole, pharmaceutical compositions containing these compounds and methods of making the same - Google Patents

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Description

Benzimidazole, pharmaceutical compositions containing these compounds and methods of making the same

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Claims (10)

Formula (I) is benzimidazole, its 1-, 3-isomer mixtures and addition salts thereof with inorganic or organic acids or bases. Wherein R ₁ in the 4-position represents a fluorine, chlorine or bromine atom C _1-4 -alkyl, cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group, and R ₂ is an imidazolyl group Or a C _3-5 -alkoxy group substituted at the 3-, 4- or 5-position by R ₂ is a 2-, 3-, 4- by a benzimidazolyl or tetrahydrobenzimidazolyl group Or a C _2-5 -alkoxy group substituted at the 5-position, or when R ₄ represents a 1H-tetrazolyl group, R ₂ also represents a 2- (imidazol-1-yl) -ethoxy group Can be represented; C _1-4 -alkylsulfonyloxy group, benzenesulfonyloxy or phenylalkanesulfonyloxy group; C _1-6 -alkyl group or phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group An acylamino group optionally substituted at the nitrogen atom by the acyl group is a C _1-7 -alkanoyl group, C _2-4 (alkoxycarbonyl) group, C _1-6 -alkylsulfonyl group, benzoyl, benzene Sulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl groups, the aforementioned phenyl nuclei being understood as fluorine, chlorine or bromine atoms or methyl or methoxy groups, respectively. Or may be disubstituted and the substituents may be the same or different); Phthalamino, homophthalamino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino groups, wherein the carbonyl group in the phthalimino group may be substituted by methylene, alkyl methylene or dialkyl-methylene groups And in the homophthalimino group the methylene group can be substituted by one or two alkyl groups, and further the aforementioned phenyl nucleus can be mono- or di-substituted by alkyl or alkoxy groups, while the substituents are identical Or different and may be hydrogenated in whole or in part at the same time); 5-, 6- or 7-membered alkyleneamino or alkenyleneamino groups optionally substituted by one or two alkyl groups or lamethylene or pentamethylene groups, wherein the methylene group is substituted by a carbonyl or sulfonyl group Can be); Bicycloalkane-2,3-dicarboxylic acid amino or bicyclo alken-2,3-dicarboxylic acid amino groups, wherein the bicycloalkyne and bicycloalkene residues may each contain 9 or 10 carbon atoms; May be substituted by 1,2 or 3 methyl groups and may have an endomethylene group replaced by an oxygen atom); Amino groups optionally substituted by one or two C _1-6 alkyl groups; Glutaric acid amino groups, wherein the n-propylene group may be perfluorinated but may be substituted by one or two alkyl groups or tetramethylene or pentamethylene groups; Maleic acid imido groups optionally mono- or di-substituted by alkyl or phenyl groups, wherein the substituents may be the same or different; Represents a 5-membered heteroaromatic ring bound by a carbon atom or an amino group and containing an amino group, an oxygen or sulfur atom, or an amino group and an oxygen, sulfur or nitrogen atom, or R ₂ is bonded by a carbon atom and 1 6-membered heteroaromatic rings containing two or two nitrogen atoms, wherein the heteroaromatic rings described above may be substituted by C _1-6 alkyl or phenylalkyl groups in the carbon structure, or n-propenyl or n-butylene The group may be bonded to the 6-membered heteroaromatic ring by two carbon atoms, or the 1,3-butadienyl group may be bonded to the 5-membered and 6-membered heteroaromatic ring by two adjacent carbon atoms Or n-butylene or 1,3-butadienyl group is connected here by an amino group and an adjacent carbon atom, and in the thus formed anelated pyried ring the methyl group is replaced by a nitrogen atom. And the vinylene group can be replaced by a sulfur atom in the 3-, 4-position to the nitrogen atom of the formed pyridine ring, or in the so-formed annealed phenyl ring, one or two methine groups are N-atoms Wherein the fused aromatic or heteroaromatic rings described above are further substituted with fluorine, chlorine or bromine atoms in the carbon structure; or alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alka Noylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl alkylaminocarbonyl, dialkylaminocarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosul Mono-substituted by phonyl or dialkylaminosulfonyl groups or disubstituted by fluorine or chlorine atoms or methyl, methoxy or hydroxy groups, Two methyl substituents at the 1,2-position may be bonded by methylene or ethylene bridges and optionally present in the imidazole ring to a C _1-6 alkyl group, a phenylalkyl group or a cycloalkyl group. May be substituted); Or a pyrrolidine, piperidine or pyridine ring bonded by a carbon atom, wherein the phenyl group can be condensed in a cyclic ring which is pyrided by two adjacent carbon atoms and in the pyrrolidine or piperidine ring Methylene groups adjacent to can be replaced by carbonyl groups); Imidazolidinedione groups optionally substituted by alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene groups; Pyridazin-3-one or dihydro-pyridazin-3-one groups which may be optionally substituted in the 2-position by a phenyl substituted alkyl group in the carbon structure and further by one or two alkyl groups; R ₇ -NR ₆ -CO-NR ₅ -group wherein R ₅ represents a hydrogen atom, a C _1-8 alkyl group, a C _5-7 cycloalkyl group or a phenylalkyl group, and R ₆ represents a hydrogen atom, C _{1 -8 represents an} alkyl group, a C _3-5 alkenyl group, a phenyl group, a phenyl alkyl group or a C _5-7 -cycloalkyl group, R ₇ represents a hydrogen atom or a C _1-6 -alkyl group, or a group R _{One of 5} , R ₆ or R ₇ may also represent a bicyclohexyl or biphenyl group or R ₆ and R ₇ are unbranched C _4-6 -alkyleneamino groups or moles with a nitrogen atom between them Represents a polyno group or R ₅ and R ₆ together represent a C _2-4 -alkylene group), or R ₂ represents 1H, 3H-quinazolin-2,4-dione-3-yl or pentamethylene May represent an oxazolin-2-yl group or R ₁ represents a hydrogen atom, or R ₁ is a fluorine, chlorine, or bromine atom, a C _1-4 alkyl group at the 5-, 6- or 7-position; Can represent a fluoromethyl, difluoromethyl or trifluoromethyl group and R ₂ is bonded by a carbon atom or an imino group and represents an imino group, an oxygen or sulfur atom or an amino group and an oxygen, sulfur or nitrogen atom. Or a _2- membered heteroaromatic ring, or R ₂ is bonded by a carbon atom, and a 6-membered heteroaromatic ring containing one or two nitrogen atoms, wherein the heteroaromatic rings described above are May be substituted by a C _1-6 -alkyl or phenyl group and the n-propylene or n-butylene group may be bonded to a 6-membered heteroaromatic ring by two carbon atoms or a 1,3-butadienyl group Silver may be linked by two carbon atoms adjacent to a 5-membered and 6-membered heteroaromatic ring, or n-butylene or 1,3-butadienyl group may be selected from the 5-membered and 6-won In the anelated pyridine ring thus formed, which can be linked to a heteroaromatic ring, the methyl group can be replaced by a nitrogen atom and the vinylene group at the 3-, 4-position relative to the nitrogen atom of the formed pyridine ring by a sulfur atom In the anylated phenyl ring so formed or so formed, one or two methine groups can be replaced by N-atoms and further the fused aromatic or heteroaromatic rings described above are fluorine, chlorine or bromine in the carbon skeleton. Atoms, or alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl , By fluoromethyl, difluoromethyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylamino sulfonyl groups Can be substituted or disubstituted by fluorine or chlorine atoms or methyl, methoxy or hydroxy groups, two methyl substituents at 1,2-positions relative to one another can be bonded by methylene or ethylene bridges and imidazole rings May optionally be substituted by a C _1-6 -alkyl group, phenylalkyl group or cycloalkyl group, provided that (i) R ₁ represents a hydrogen atom and R ₃ represents an n-propyl group When R ₄ represents a carboxy group, R ₂ is 3-methyl-imidazol [4,5-b] pyridin-2-yl or 3-n-hexyl-imidazo [4,5- at the 6-position; b] if a pyridin-2-yl group cannot be represented or (ii) R ₁ represents a hydrogen atom, R ₃ represents an n-propyl or n-butyl group and R ₄ represents a 1H-tetrazolyl group, then R ₂ or may represent a benzo-2-yl group in the 5-or 6-position, (ⅲ) R ₁ is hydrogen Character indicates, R ₃ cases showing a n- propyl group, R ₄ represents a carboxyl group, R ₂ is a 5- or 6- positions can not represent a 1-methyl-l, imidazol-2-yl group at the 6-position 1 -n-butyl-benzimidazol-2-yl, 1,5-dimethylbenzimidazol-2-yl or 1-methyl-5-trifluoro methyl-benz amidazol-2-yl group cannot be represented, or (Iii) when R ₁ represents a hydrogen atom, R ₃ represents an n-butyl group, and R ₄ represents a carboxy group or a 1H-tetrazolyl group, R ₂ represents 1-methylbenzimidazole- at the 6-position; (I) when R ₁ represents a hydrogen atom, R ₃ represents an n-butyl group and R ₄ represents a carboxy group, whether or not a 2-yl group can be represented, R ₂ is benzimidazole- ₂ at the 6-position; -Represents a one group, or R ₂ is a pyrrolidine or pyridine ring bonded by a carbon atom, wherein the phenyl group is two adjacent carbon Can be condensed in the pyridine ring and methylene group adjacent to the nitrogen atom in the pyrrolidine or piperidine ring can be replaced by a carbonyl group), and R ₃ represents a hydrogen atom or C _{1- 5} -alkyl group, wherein methylene group can be replaced by sulfur atom, or R ₃ can represent C _3-5 cycloalkyl group, R ₄ is carboxy, cyano, 1H-tetra Zolyl or 1-triphenylmethyl tetrazolyl group, C _2-5 (alkoxycarbonyl) group, alkanesulfonyl iminocarbonyl, arylsulfonylamino-carbonyl or trifluoro methanesulfonylaminocarbonyl group, Unless stated otherwise, the alkanoyl, alkyl or alkoxy moieties described above may in each case contain 1 to 3 carbon atoms and the aforementioned cycloalkyl moieties may in each case contain 3 to 7 carbon atoms. The compound of claim 1, wherein R ₁ represents a fluorine, chlorine or bromine atom C _1-3 -alkyl group, a cycloalkyl, fluoromethyl or difluoromethyl or trifluoromethyl group at the 4-position, and R ₂ is C _3-5 -alkoxy group substituted at the 3-, 4- or 5-position by an imidazolyl group, or R ₂ is 2-, 3 by a benzimidazolyl or tetrahydrobenzimidazolyl group A C _2-5 -alkoxy group substituted at the —, 4- or 5-position; _Acylamino group optionally substituted with a nitrogen atom for a C _1-5 -alkyl group wherein the acyl group is a C _2-7 -alkanoyl group, a C _2-4 (alkoxycarbonyl) group, C _1-3 -alkyl Sulfonyl group or benzenesulfonyl group), phthalimino, homophthalamino group wherein carbonyl group in phthalimino group can be substituted by methylene group and methylene in homophthalamino group Or may be substituted by two alkyl; 5-, 6- or 7-membered alkyleneimino or alkenyleneamino group optionally substituted by one or two alkyl groups or tetramethylene or pentamethylene groups Methylene groups may be replaced by carbonyl or sulfonyl groups; glutaric acid amino groups, where n-propylene groups are perfluorinated, or one or two alkyl groups or tetramethylene or pentamethylene groups By Chi By alkyl or phenyl group optionally mono- or di-substituted maleic acid amido group (wherein the substituents may be the same or different);; there can) be by one or two C _1-4 alkyl groups An optionally substituted amidino group; a benzimidazol-2-yl group optionally substituted at the 1-position by a C _1-6 -alkyl or cycloalkyl group, wherein the phenyl nucleus of any of the benzimidazole groups May be further substituted by fluorine atom or methyl or trifluoromethyl group), or R ₂ is imidazo [2, 1-b] thiazol-6-yl, amidazo [1,2-a ] Pyridin-2-yl, 5,6,7,8-tetrahydro-imidazo [1,2, -a] pyridin-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] -pyridin-2-yl imidazo [4,5-c] pyridin-2-yl, purin-8-yl, imidazo [4, 5-b] pyridin-2-yl, or amidazo [4,5-d] pyridazin-2-yl groups, or carbon-bonded pyrrolidine, piperidine or pyridine rings, wherein the phenyl group is 2 Methylene groups condensed in the pyridine ring by two adjacent carbon atoms and adjacent to the N- atom in a pyrrolidine or piperidine ring can be replaced by a carbonyl group); by C _1-3 -alkyl groups or benzyl groups Carbon-bonded amidazolyl groups which may be optionally substituted in the 1-position and also substituted by C _1-3 alkyl groups in the carbon skeleton; Imidazolidinedione groups optionally substituted by alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene groups; Pyridazin-3-one or dihydro-pyridazin-3-one groups which may be substituted by methyl or benzyl groups in the 2-position; R ₇ -NR ₆ -CO- group wherein R ₅ represents a hydrogen atom, a C _1-5 -alkyl group, a cyclohexyl or benzyl group, R ₆ represents a hydrogen ledger, a C _1-6 -acyl group, allyl, C _4-6 -alkyl which represents a cyclohexyl, benzyl or phenyl group, R ₇ represents a hydrogen atom or a C _1-3 -alkyl group, or R ₅ and R ₇ are unbranched with a nitrogen atom between them Rhenimino group or morpholino group or R ₅ and R ₆ together represent a C _2-3 -alkylene group), or R ₁ represents a hydrogen atom or 5-, 6- or 7- In which R ₁ may represent a fluorine, chlorine or bromine atom, a C _1-4 -alkyl group or a fluoromethyl group and R ₂ is optionally substituted by a C _1-6 -alkyl group or a cycloalkyl group in the 1-position Benzimidazol-2-yl group, wherein one of the aforementioned benzimidazole groups is a fluorine atom or a methyl or May be further substituted by a methyl group, trifluoromethyl, R ₂ is 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] 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- 2-yl, amidazo [4,5, -c] pyridazin-2-yl or amidazo [4,5-d] pyrazin-2-yl groups, or carbon-bonded pyrrolidine, paperidine or The pyridine ring, wherein the phenyl group can be condensed in the pyridine ring by two adjacent carbon atoms and the methylene group adjacent to the N-atom in the pyrrolidine or piperidine ring is a carbonyl group or a C _1- at 1 position. Optionally substituted by ₃ alkyl groups or benzyl groups Substituted with a carbon-bonded imidazolyl group, which may also be substituted and substituted by C _1-3 alkyl groups in the carbon backbone, provided that (i) R ₁ represents hydrogen and R ₃ represents n- When a butyl group and R ₄ represents a carboxy group, R ₂ cannot represent a benzimidazol-2-yl group at the 6-position and R ₂ is a C _1-5 -alkyl group or C _3-5 -cyclo Alkanoyl, alkyl or alkoxy moieties mentioned above, in each case containing 1 to 3 carbon atoms, and cycloalkyl as described above, wherein R ₄ is a carboxy or 1H-tetrazolyl group The residue is in each case benzimidazole of formula (I), which may contain 3 to 7 carbon atoms, a mixture of 1-, 3-isomers thereof and addition salts with inorganic or organic acids or bases thereof. The compound of claim 1, wherein R ′ represents a chlorine atom or a C _1-3 -alkyl group or a trifluoromethyl group at the 4-position and R ₂ is at the 3-, 4- or 5-position by an imidazolyl group. C _2-5 -which represents a substituted C _3-5 -alkoxy group or R ₂ is substituted at the 2-, 3-, 4- or 5-position by benzimidazolyl or tetrahydrobenzimidazolyl group Alkoxy group; C _2-5 (alkanoyl) imino group or N-benzenesulfonylmethylamino group, phthalimino, or homophthalimino group, wherein the carbonyl group in the phthalamino group may be substituted by a methylene group 5-, 6- or 7-membered alkyleneamino group, wherein the methylene group is substituted by a carbonyl or sulfonyl group; Glutaric acid amino groups, wherein the n-propylene group may be substituted by one or two alkyl groups or tetramethylene or pentamethylene groups; Maleic acid imido groups, optionally mono- or di-substituted by alkyl or phenyl groups, wherein the substituents may be the same or different; Benzimidazol-2-yl groups optionally substituted at the 1-position by a C _1-6 -alkyl or cycloalkyl group, wherein the phenyl nucleus of one of the benzimidazole groups described above is a fluorine atom or a methyl or trifluoro May be further substituted by a methyl group), and R ₂ is imidazo [2,1-b] thiazol-6-yl, imidazo [1,2-a] pyridin-2-yl, 5 , 6,7,8-tetrahydro-amidazo [1,2, -a] pyridin-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] pyrimidin-2-yl, imidazo [1,2-a] pyrazine-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 amidazo [4,5-d] pyridazin-2-yl group, or carbon-bonded pyrrolidine, piperi Dine or pyridine ring, wherein the phenyl group is two adjacent carbons It is condensed on the pyridine ring by those pyrrolidine or piperidine methylene group adjacent to the N- atom Dean ring may be replaced by a carbonyl group), C _1-3 - alkyl groups or by a benzyl group, 1- Amidazolyl-4-yl groups which may be substituted in the position and also substituted by C _1-3 -alkyl groups in the carbon skeleton; Pyridazin-3-one or dihydro-pyridazin-3-one which may be substituted by a methyl or benzyl group at the 2-position; R ₇ -NH ₆ -CO-NR ₅ -group wherein R ₅ represents a hydrogen atom, a C _1-5 alkyl group, a cyclohexyl or a benzyl group, and R ₆ represents a hydrogen atom, a C _1-6 alkyl group, allyl C _4-5 -alkyl which represents a cyclohexyl, benzyl or phenyl group, R ₇ represents a hydrogen atom or a C _1-3 -alkyl group or R ₆ and R ₇ are unbranched with a nitrogen atom between them Lene imino group or morpholino group, or R ₅ and R ₆ together represent a C _2-3 -alkylene group), or R ₁ represents a hydrogen atom or 5-, 6- or 7- Or benzimidazole-2- in which R ₁ may represent a C _1-4 -alkyl group or a fluoromethyl group and R ₂ is optionally substituted by a C _1-6 -alkyl group or a cycloalkyl group in the 1-position; A phenyl nucleus of one of the above-described benzimidazole groups to a fluorine atom or to a methyl or trifluoromethyl group May be further substituted, or R ₂ , is imidazo [2,1-b] thiazol-6-yl, amidazo [2,1-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, already Multizo [4,5-c] pyridazin-2-yl, or imidazo [4,5-d] pyridazin-2-yl groups, or carbon-bonded pyrrolidine, piperidine or pyridine rings, wherein The phenyl group may be condensed in the pyridine ring by two adjacent carbon atoms, and the methylene group adjacent to the N-atom in a pyrrolidine or piperidine ring may be substituted by a carbonyl group); Or an amidazolyl-4-yl group which may be substituted by a C _1-3 alkyl group or benzyl group in the 1-position and also substituted by a C _1-3 alkyl group in the carbon skeleton, provided that (V) When R ₁ represents hydrogen, R ₃ represents an n-butyl group and R ₄ represents a carboxy group, R ₂ cannot represent a benzimidazol-2-yl group at the 6-position and R ₃ is C _1- Benzimidazoles of the general formula (I), a 1-, 3-isomer mixture thereof and an inorganic thereof or a ₅ -alkyl group or a C _3-5 -cycloalkyl group, wherein R ₄ represents a carboxy or 1H-tetrazolyl group Addition salts with organic acids or bases. The compound of claim 1, wherein R _{1 at the} 4-position represents a methyl group or a chlorine atom, and R ₂ represents a C _3-5 -alkoxy group substituted at the 3-, 4- or 5-position by an imidazolyl group. Or a C _2-5 -alkoxy group where R ₂ is substituted at the 2-, 3-4- or 5-position by a benzimidazolyl or tetrahydrobenzimidazolyl group; C _2-5 (alkanoyl) imino group or N-benzenesulfonylmethylimino group, phthalimino, or homophthalimino group, wherein in the phthalimino group the carbonyl group is substituted by a methylene group Can be); 5-6- or 7-membered alkyleneamino group, wherein the methylene group may be substituted by a carbonyl or sulfonyl group; Maleic acid imido group optionally substituted with an alkyl or phenyl group, wherein the substituents may be the same or different, and benzimidazole optionally substituted at the 1-position by a C _1-3 -alkyl group Or a 2-yl group wherein the phenyl nucleus of one of the benzimidazole groups described above may be further substituted by a fluorine atom, or R ₂ is imidazo [2,1-a] pyridin-2-yl Group, 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridin-2-yl, imidazo [1,2-a] pyrimidin-6-yl, or imidazo [2, 1-b] thiazol-6-yl group; Amidazolyl-4-yl group substituted at the 1-position by C _1-3 alkyl group, pyridazin-3-one or dihydro-pyridazine- which may be substituted by the methyl or benzyl group at the 2-position A tri-ion group, R ₁ may represent a hydrogen atom or R ₁ may represent a methyl group at the 5-, 6- or 7-position, and R ₂ may be a C _1-3 -alkyl group at the 1-position Or a benzimidazol-2-yl group optionally substituted by, wherein the phenyl nucleus may be further substituted by a fluorine atom, or R ₂ is in the 1-position by a C _1-3 alkyl group Substituted imidazo [2,1-a] pyridin-2-yl group, imidazol-4-yl group, (V) R ₁ represents hydrogen, R ₃ represents n-butyl group and R ₄ When R represents a carboxy group, R ₂ cannot represent a benzimidazol-2-yl group at the 6-position and R ₃ is a C _1-5 -alkyl group or C _3-5 -cycloalkyl Benzimidazoles of the general formula (I), a 1-, 3-isomer mixture thereof, and an addition salt thereof with an inorganic or organic acid or base, wherein the group is represented and R ₄ represents a carboxy or 1H-tetrazolyl group. The compound of claim 1, wherein (a) 4 ′-[[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl] -methyl] -Biphenyl-2-carboxylic acid, (b) 4 '-[[2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl]- Methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (c) 4 '-[[2-n-propyl-4-methyl-6- (1-oxo-isoindolin-2- Yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, d) 4 '-[[2-n-propyl-4-methyl-6- (Butanesultam-1-yl) -benzimidazol-1-yl] -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (e) 4 '-[[2-n-butyl -6- (2,3-dimethylmaleic acid) -4-methylbenzimidazol-1-yl] -methylbiphenyl] -2-carboxylic acid, (f) 4 '-[[2-n-butyl-6 -(Isopropylcarbonylamino) -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid, (g) 4 '-[[2-n-butyl-4-methyl- 6- (morpholinocarbonylimino) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid, (h) 4 '-[[2-n-butyl-6- (cyclohexyl Iminocarbonyl Mino) -4-methyl-benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid, (i) 4 '-[[2-cyclopropyl-4-methyl-6- (1-methylbenz) Imidazol-2-yl) -benzimidazol-1-yl] -biphenyl-2-carboxylic acid, (j) 4 ′-[(2-n-propyl-4-methyl-6- (1-methyl-5) -Fluoro-benzimidazol-2-yl) -benzimidazol-1-yl-methyl] -biphenyl-2-carboxylic acid, (k) 4 '-[(2-n-propyl-4-methyl-6 -(Imidazo [1,2-a] pyrimidin-2-yl) -benzimidazol-1-yl) -2 (1H-tetrazol-5-yl) -biphenyl, (l) 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, (m) 4 ′-[(2-n-propyl-4-methyl-6- (4,5,6,7-tetrahydro-imidazo [1,2-a ] Pyridin-2-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (n) 4 '-[(2-n-propyl-] 4-Chloro-6- (1-methylbenzimidazol-2-yl) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl) -biphenyl, (o) 4 '-[[2-n-propyl-4- Tyl-6- (imidazol [2,1-b] thiazol-6-yl) -benzimidazol-1-yl] -methyl] -biphenyl-2-carboxylic acid, (p) 4 ′-[[2 -Ethyl-4-methyl-6- (butanesultam-1-yl) -benzimidazol-1-yl) -methyl] -2- (H1-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] pyridine- 2-yl) -benzimidazol-1-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) -benzimidazol-1-yl) -methyl] -2- (1H-tetrazol-5-yl ) -Biphenyl and (v) 4 ′-[(2-n-propyl-4-methyl-6- (1-methyl-6-fluoro-benzimidazole-2 Benzimidazole of formula (I), a 1-, 3-isomer mixture thereof and a salt with an inorganic or organic acid or base thereof, which is -yl) -benzimidazol-1-yl) -methyl] biphenyl. The physiologically acceptable addition salt of a compound according to any one of claims 1 to 5, wherein the compound is an inorganic or organic acid or base. A pharmaceutical composition containing a compound according to any one of claims 1 to 5 and a physiologically acceptable addition salt according to claim 6, optionally with at least one inert carrier and / or diluent. Use of a compound according to any one of claims 1 to 6 for the preparation of a pharmaceutical composition having angiotensin-antagonist activity. A process for preparing a pharmaceutical composition according to claim 8, characterized in that the compound according to claim 1 is incorporated into one or more inert carriers and / or diluents by non-chemical methods. a) closing the compound of formula (II) and reducing the corresponding N-oxide so obtained, or b) reacting benzimidazole of formula (III) with a biphenyl compound of formula (IV) or c) to prepare a compound of formula (I) wherein R ₄ represents a carboxy group, converting the compound of formula (V) to the corresponding carboxy compound, or d) R ₄ to a 1H-tetrazolyl group To prepare the compound of general formula (I), the protecting group is separated from the compound of general formula (VI), or e) to prepare a compound of general formula (I) wherein R ₄ represents a 1H-tetrazolyl group. To this end, the compound of general formula (VII) is reacted with hydrazonic acid or a salt thereof, or f) R ₂ is imidazo [1,2-a] -pyridine, as mentioned in any one of claims 1 to 5. -2-yl, imidazo [1,2-a] pyrimidin-2-yl, imidazo [1,2-c] pyrimidin-2-yl, imidazo [1,2-a] pyrazine-2 -Work To prepare a compound of formula (I) representing one of the imidazo- [1,2-b] pyridazin-2-yl, or imidazo [2,1-b] thiazol-6-yl groups Or reacting a compound of formula (VIII) with a compound of formula (VIII), or g) R ₂ is benzimidazol-2-yl, imidazo [4] according to any one of claims 1 to 5. , 5-b] pyridin-2-yl, imidazo [4,5-c] pyridin-2-yl, imidazo [4,5-b] pyrazin-2-yl, imidazo [4,5-c] To prepare a compound of formula (I) representing one of the pyridazin-2-yl, imidazo [4,5-d] pyridazinyl or furin-8-yl groups, the compounds of formula to ring-closure and a corresponding reduction of the N- oxide and optionally subsequently hydrolyzing the thus obtained compound to obtain, or, h) R ₂ is a C _1-3 optionally substituted by a phenyl group at the 2-position - by alkyl groups , Or one or two carbon atoms of 1 to 3 in the carbon structure Dihydro-pyridazin-3-ones or pyridazin-3-ones, which may be substituted by alkyl groups, are used to prepare compounds of formula (I) representing groups, the carboxylic acids of formula (XII) or esters thereof , Reacting reactive acid derivatives such as amides or halides with hydrazines of the general formula (XIII) and optionally separating the protecting groups used during reactions a) to h) to protect the reactive groups and / or The 1-, 3-isomer mixture of the obtained compound of general formula (I) is decomposed into 1- and 3-isomers by isomeric separation or the compound of general formula (I) thus obtained is an addition salt thereof, more particularly pharmaceutical A process for the preparation of benzimidazoles according to claims 1 to 6, characterized in that it is converted to a salt with a physiologically acceptable inorganic or organic acid or base for its use. Wherein R ₁ , R ₂ , R ₃ , R ₄ are as defined in claims 1 to 5, wherein one of groups X ₁ or Y ₁ is a general formula Represents a group of and another group X ₁ or Y ₁ is Wherein R ₂ and R ₄ are as defined in claims 1 to 5, R ₈ represents a hydrogen atom or an R ₃ CO-group (wherein R ₃ is as defined above), Z ₁ and Z ₂ are the same or different and optionally substituted amino group or hydroxy; Or a mercapto group optionally substituted by a lower alkyl group or Z ₁ and Z ₂ together are an oxygen or sulfur atom, optionally a C _1-3 -alkylsubstituted amino group, alkylenedioxy having 2 or 3 carbon atoms each, or Alkylenedithio group], but one of the groups X ₁ or Y ₁ or Represent a leaving group and Z ₃ denotes a nucleophilic R ⁴ 'represents a group which can be converted into a carboxy group by hydrolysis, thermal decomposition or hydrogenolysis ^4〃 R is 1- or protective group at the 3-position Represents a 1H-tetrazolyl group protected by Z ₄ represents a nucleophilic leaving group such as a halogen atom, for example chlorine or bromine atom, and one of groups A, B, C or D represents a methine group or a nitrogen atom The remaining groups A, B, C or D represent methine groups or A and B each represent methine and the -C = D- group represents a sulfur atom, R ⁹ represents hydrogen, fluorine, chlorine or bromine atom or alkyl , Alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, (dialkyl, amino) alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, tri Fluorome Butyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkyl aminosulfonyl groups, R ¹⁰ represents hydrogen, fluorine or chlorine or methyl, methoxy or hydroxy groups and R ₉ and R ₁₀ are adjacent In the case of methyl groups, these may be linked together to methylene or ethylene groups, where 0, 1 or 2 of the groups A ₁ , B _1, C ₁ or D ₁ represent nitrogen atoms and the remaining groups group A ₁ , B _1, C ₁ or D ₁ represents a methine group, R ₁₁ represents hydrogen fluorine, chlorine or bromine atom or alkyl, alkoxy hydroxy phenyl, nitro, amino, alkylamino, dialkyl amino, alkanoylamino, cyano, carboxy , Alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, amino sulfonyl, alkylaminosulfonyl or dialkylamino sulfonyl group, R ₁₂ represents a hydrogen, fluorine or chlorine atom or a methyl, methoxy or hydroxy group, one of groups X ₂ or Y ₂ represents a R ₁₃ -NH- group and another X ₂ or Y ₂ group is a general formula Wherein R ₁ , R ₃ and R ₄ are as defined in any one of claims 1 to 5 and one of the groups R ₁₃ or R ₁₄ represents a hydrogen atom or the R ₁₃ or R ₁₄ group represents a hydrogen atom, C _1-6 -alkyl group or cycloalkyl group, Z ₅ and Z ₆ represent the same or different and optionally substituted amino group or mercapto group optionally substituted by hydroxy or lower alkyl group, Z ₅ and Z ₆ together represent an oxygen or sulfur atom, optionally a C _1-3 -alkyl substituted amino group, an alkylene dioxy or alkylenedithio group each having 2 or 3 carbohydrates and E is one or two of C _1-3 represents the ethylene or ethylene group optionally substituted with an alkynyl group, R ₁₅ is a hydrogen atom or a C _1-3 optionally substituted by a phenyl group - represents an alkyl group. ※ Note: The disclosure is based on the initial application.