HK1011145B - Benzimidazol derivatives, medicaments containing them and process for their preparation - Google Patents

Description

Benzimidazoles, which are angiotensin II antagonists, are already described in European disclosures 0,468,470, 0,459,136 and 0,420,237, which are only partially a preliminary publication, and in EP-A-0,400,835, EP-A-0,399,732 and US-A-4,880,804.

It has now been found that the new benzimidazole of the general formula whereas these are always distinguished from the benzimidazoles described in the disclosure notes mentioned above by the residual R2 and the compounds of general formula I, where R2 means a pyridyl or imidazoyl group, represent a sample from EP-A-0,400,835 and are even more valuable angiotensin II antagonists than those known in the literature.

The present invention thus relates to the new benzimidazoles of the above general formula I and their salts, in particular their salts physiologically compatible with inorganic or organic acids or bases for pharmaceutical use, medicinal products containing these compounds and methods for their manufacture.

In the above general formula I means a fluorine, chlorine or bromate group, an alkyl, cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group,R2 a 5-, 6- or 7-membered alkyl- or alkene-aminine group, wherein a methyl group is replaced by a carbonyl or sulphonyl group,whether or not substituted by an alkyl- or trifluoromethyl group,R2 a substituent group, wherein the phenyl group may be different or equivalent, a carbonyl group, wherein a carbonyl group may be substituted by an alkyl group up to 6 or a tetramethyl or pentamethyl group, or by a cycloalkyl group up to 6 or a cycloalkyl group, wherein a cycloalkyl group is substituted by a hydroxy group,[1, 2, 1, 2, 1, 2, 1, 2, 2, 3, 4, 4, 5, 6, 7, 8, 8, 9, 10, 11, 12, 12, 12, 13, 13, 13, 13, 13, 14, 14, 14, 14, 15, 15, 16, 19, 19, 19, 19, 19, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, 20, and so on the other parts of

For the meanings mentioned at the beginning of the definition of the residues R1 to R3, for example, R1 the meaning of the fluorine, chlorine or bromate atom, the methyl, ethyl, n-propyl, isopropyl, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butanidine, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, butan, but, butan, butan, but, butan, butan,

The preferred compounds of the above general formula I are those in which: 1 a chlorine atom, an alkyl group with 1 to 3 carbon atoms or a trifluoromethyl group,R2 an alkyl aminogroups of 5, 6 or 7 members in which a methyl group is replaced by a carbonyl or sulphonyl group,a methyl group with 1 to 3 carbon atoms or a phenyl group,which may be a mono- or displaced maleic acid group, where the substituents may be the same or different,a substitution, where applicable, in 1-styl, by an alkyl group with 1 to 6 carbon atoms or a cyclo-2-aminogroups, where the methyl group is replaced by a carbonyl group or a carbonyl group, up to 4,5,6-methyl-2-methyl group, where the methyl group is replaced by a carbonyl group, or by a benzene group up to 4,5-methyl group, or by a benzene group up to 5,5-methyl group, which may be a benzene group, or a benzene group up to 4,5-methyl group, where the benzene group is replaced by a benzene group, which may be a benzene group, an oxalazine group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an oxalate group, an enzyme, an enzyme, an enzyme, an enzyme, an enzyme, an en, an en, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an, an

Particularly preferred compounds of the above general formula I are those in whichR1 is a methyl group or a chlorine atom,R2 is a 5-, 6- or 7-membered alkyl aminogroups in which a methyl group is replaced by a carbonyl or sulphonyl group,one may be an alkyl group containing 1 to 3 carbon atoms or a phenyl group mono- or displaced maleic acid amide group, where the substituents may be the same or different,one may be in 1 position by an alkyl group containing 1 to 3 carbon atoms substituted by a benzimin-2-methyl group or 4,5,6,7-tetrahydrozoamide amide group, where the phenyl amide group containing 1 to 3 carbon atoms or by a phenyl amide group substituted by an amide group, or a 1-,6,6-tetrahydrozoamide amide group substituted by a 5-,6,6-tetrahydrozoamide amide group, where the phenyl amide group may be substituted by an amide group, or a 3-,5-,6-,5-[4,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,6-,

The compounds of the invention are obtained by the following processes:a) Cycling of a compound of the general formula In the R1 and R2 as defined at the beginning, one of the residues X1 or Y1 a group of the general formula and the other of the residues X1 or Y1 a group of the general formula The Commission has R3 and R4 as defined at the beginning, R8 a hydrogen atom or R3CO group, where R3 is defined as above, Z1 and Z2, which may be the same or different, substituted amino groups, where appropriate, or hydroxy or mercapto groups, where appropriate, substituted with lower alkyl groups; or Z1 and Z2, together, an oxygen or sulphur atom, an amino group, if any, substituted by an alkyl group with 1 to 3 carbon atoms,an alkyllendioxide or an alkyllendiethy group with two or three carbon atoms each, but one of the residues X1 or Y1 being a group of the general formula; or The results of the analysis shall be as follows: Cycling is carried out, where appropriate, in a solvent or a solvent mixture such as ethanol, isopropanol, ice vinegar, benzene, chlorobenzol, toluene, xylol, glycol, glycol monomethylether, diethylene glycoldimethylether, sulfolane, dimethylformamide, tetralin or in an excess of the acyclic acid used to produce the compound of general formula II, e.g. in the corresponding nitrile, anhydride, acid halide, ester or amide, for example at temperatures between 0 and 250 °C, but preferably at the boiling point of the reaction mixture, where appropriate in the presence of a condensing agent such as phosphochloroxyphospholipid,Thionyl chloride, sulphur chloride, sulphuric acid, p-toluol sulphonic acid, methane sulphonic acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, acetic anhydride or, where appropriate, in the presence of a base such as potassium methylate or potassium butylate. Other However, the most advantageous way of implementing this is to produce a compound of general formula II in the reaction mixture by reducing a corresponding o-nitro-amin compound in the presence of a carbon acid of general formula R3COOH, where appropriate, or by acylation of a corresponding o-diamine compound.Other Other Subsequent reduction of the resulting N-oxide of formula I is preferably carried out in a solvent such as water, water/ethanol, methanol, ice vinegar, acetic acid ethyl ester or dimethyl formamide with hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium/coal, with metals such as iron, zinc or zinc in the presence of an acid such as acetic acid, hydrochloric acid or sulphuric acid, with salts such as iron-II sulphate, zinc-II chloride or sodium nitrite, or with hydrazine in the presence of Raney nickel at temperatures between 0 and 50 °C, but preferably at room temperature. (b) Transformation of a benzimidazole from the general formula In the R1 to R3 as defined above, with a biphenyl compound of general formula In the R4 as defined at the beginning; and Z3 a nucleophilic leaving group such as a halogen atom,For the purposes of this Regulation, the term 'substitute' means a substance that is a mixture of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which are mixtures of substances which mixtures of substances which are mixtures of substances which mixtures of substances which are mixtures of substances which mixtures of substances are mixtures of which mixtures of substances of which are mixtures of which are mixtures of which are mixtures of substances of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are mixtures of which are both of which are both of which are both of which are both of which are both of which are both of which are both of which are both of which are of which are both of which are both of which are both of which are both of which are both of which are both of which are of which are both of which are both of which are both of which are both of which are both of which are both of which are both of which are both of which are The implementation shall be carried out, where appropriate, in a solvent or a solvent mixture such as methyl chloride, diethyl ether, tetrahydrofuran, dioxane, dimethyl sulfoxide, dimethyl formamide or benzene, where appropriate in the presence of an acid-binding agent such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium tert-butylate, triethylamine or pyridine, the latter two being also used as solvents at the same time, preferably at temperatures between 0 and 100 °C, e.g. between room temperature and 50 °C. Other The implementation preferably results in a mixture of the 1 and 3 isomers which are then separated into the corresponding 1 and 3 isomers, preferably chromatographically, using a carrier such as silica gel or aluminium oxide.Other (c) For the preparation of a compound of general formula I, where R4 is a carboxy group: Transposition of a compound of the general formula In the R1 to R3 as defined at the beginning; and R4' is a group which can be converted into a carboxy group by hydrolysis, thermolysis or hydrogenolysis. Other For example, functional derivatives of the carboxy group such as their unsubstituted or substituted amides, esters, thiolesters, orthoesters, amino ethers, amidines or anhydrides, the nitrile group or the tetrazolyl group can be converted by hydrolysis to a carboxy group, esters with tertiary alcohols, e.g. tert butyl esters, to a carboxy group by thermolysis and esters with aralkanols, e.g. benzyl esters, to a carboxy group by hydrogenolysis. Other The hydrolysis is preferably done either in the presence of an acid such as hydrochloric acid,Sulphuric acid, phosphoric acid, trichloroacetic acid or trifluoric acid in the presence of a base such as sodium hydroxide or potassium hydroxide in an appropriate solvent such as water, water/methanol, ethanol, water/ethanol, water/isopropanol or water/dioxane at temperatures between -10°C and 120°C, e.g. between room temperature and boiling point of the reaction mixture. Other If R4' in a compound of general formula V means a cyano- or aminocarbonyl group, these groups may also be used with a nitrite, e.g. sodium nitrite, in the presence of an acid such as sulphuric acid, where appropriate used simultaneously as solvent,The test chemical is used to determine the concentration of the test chemical in the test chemical. Other If R4' in a compound of general formula V means, for example, the tert-butyloxycarbonyl group, the tert-butyl group may also be thermally cleaved, if necessary, in an inert solvent such as methylene chloride, chloroform, benzene, toluene, tetrahydrofuran or dioxane and preferably in the presence of a catalytic amount of an acid such as p-toluene sulphonic acid, sulphuric acid, phosphoric acid or polyphosphoric acid, preferably at the boiling point of the solvent used, e.g. between 40 °C and 100 °C. Other If R4' in a compound of general formula V means, for example, the benzyloxycarbonyl group, the benzyl group can also be hydrolyzed in the presence of a hydrogenation catalyst such as palladium/carbon in a suitable solvent such as methanol,Err1:Expecting ',' delimiter: line 1 column 897 (char 896)Other The protective residue may be, for example, the triphenylmethyl, tributyltin or triphenyltin group. The decomposition of a residual used protective material shall preferably be carried out in the presence of a hydrogen halogen, preferably in the presence of hydrochlorofluorocarbons, in the presence of a base such as sodium hydroxide or alcoholic ammonia in an appropriate solvent such as methylene chloride, methanol, methanol/ammonia, ethanol or isopropanol at temperatures between 0 and 100 °C, but preferably at room temperature, or, if the transformation is carried out in the presence of alcoholic ammonia, at elevated temperatures, e.g. between 100 and 150 °C, preferably between 120 and 140 °C. (e) For the preparation of a compound of general formula I, where R4 is a 1H tetrazolyl group: Implementation of a compound of the general formula In the R1 to R3 as defined at the beginning,with hydrogen nitric acid or its salts. Other The conversion is preferably carried out in a solvent such as benzene, toluene or dimethylformamide at temperatures between 80 and 150 °C, preferably 125 °C. It is appropriate to either release the hydrogen nitric acid during the conversion from an alkaline acid, e.g. sodium azide, in the presence of a weak acid such as ammonium chloride, or to release it in the reaction mixture during the conversion with a salt of the water nitric acid, preferably with aluminium azide or tributylzine azide, which are also produced in the reaction mixture by conversion of aluminium tributyl chloride or tetraethyl salt chloride with an alkaline acid, e.g. sodium azide, obtained by diluting the resulting solution with an anzoic acid such as 2N or a sulphuric acid.Other (f) For the preparation of compounds of general formula I, where R2 is one of the imidazo[1,2-a]pyridin2-yl, imidazo[1,2-a]pyrimidine-2-yl, imidazo[1,2-c]pyrimidine-2-yl, imidazo[1,2-a]pyrazin-2-yl, imidazo[1,2-b]pyridazin-2-yl or imidazo[2,1-b]thiazole-6-yl groups as mentioned above: Implementation of a compound of the general formula In the a methyl group or nitrogen atom substituted for one of the residues A, B, C or D, if applicable, and The remaining residues A, B, C or D are methane groups or A and B each are a methane group and the -C=D group is a sulphur atom, with a compound of the general formula R1, R3 and R4 as defined at the beginning; and Z4 is a nucleophilic leaving group like a halogen atom, e.g. a chlorine or bromate atom. Other The implementation shall be carried out, where appropriate, in a solvent or a mixture of solvents such as ethanol,The results of the analysis of the results of the analysis of the test chemical are presented in Table 1 of this section. (g) For the preparation of compounds of general formula I, where R2 is any of the abovementioned benzymidazole-2-yl, imidazo[4,5-b]pyridine-2-yl, imidazo[4,5-c]pyridine-2-yl, imidazo[4,5-b]pyrazin-2-yl, imidazo[4,5-c]pyridazine-2-yl, imidazo[4,5-d]pyridine-2-yl or purine-8-yl groups: Cycling of a compound of general formula In the 0, one or two of the residues A1, B1, C1 or D1 one nitrogen atom and the residues of residues of A1, B1, C1 or D1 methyl groups; and R11 a hydrogen or fluorine atom, a methyl or trifluoromethyl group, one of the residues X2 or Y2 an R13-NH group and the other of the residues X2 or Y2 a group of the general formula represent,where R1, R3 and R4 are as defined above, one of the residues R13 or R14 being a hydrogen atom and the other of the residues R13 or R14 being a hydrogen atom, an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group with 3 to 7 carbon atoms, Z5 and Z6, which may be the same or different, substituted amino groups, where appropriate, or hydroxy or mercapto groups, where appropriate, substituted with lower alkyl groups; or Z5 and Z6 together mean an oxygen or sulphur atom, an amino group, if any, substituted by an alkyl group with 1 to 3 carbon atoms, an alkyl oxide or an alkyl dinithium group with 2 or 3 carbon atoms each, and, if necessary, the subsequent reduction of the corresponding N-oxide thus obtained and, if necessary, subsequent hydrolysis.

Cycling is carried out, as appropriate, in a solvent or a solvent mixture such as ethanol, isopropanol, iron vinegar, benzene, chlorobenzol, toluene, xylol, glycol, glycol monomethylether, diethylene glycoldimethylether, sulfolane, dimethylformamide, tetralin or in an excess of the acyclic solvent used to produce the compound of generic formula X, 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, or in the presence of a condensing agent such as phospholipid, potassium chloride, sulphonylurea, butyl sulphate or butyl sulphuric acid, but also in the presence of a condensing agent such as methanol, butyl sulphate, butyl sulphuric acid or butyl sulphuric acid.

However, the most advantageous way of implementing this is to reduce a compound of general formula X in the reaction mixture by reducing a corresponding o-nitroamine compound, where appropriate in the presence of a carbonic acid of general formula X. In the R1, R3 and R4 as defined above, or is produced by acylation of a corresponding o-diamine compound with a carbonic acid of general formula XI.

When the reduction of the nitrogroups at the hydroxylamine stage is broken, the N-oxide of a compound of general formula I is obtained by subsequent cycling. The N-oxide thus obtained is then transferred by reduction to a corresponding compound of general formula I.

Subsequent reduction of the N-oxide thus obtained is preferably carried out in a solvent such as water, water/ethanol, methanol, ice vinegar, acetic acid ethyl ester or dimethylformamide with hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium/coal, with metals such as iron, zinc or zinc in the presence of an acid such as acetic acid, hydrochloric acid or sulphuric acid, with salts such as iron (II) sulphate, zinc (II) chloride or sodium diithionite, or with hydrazine in the presence of raney nickel at temperatures between 0 and 50 °C, but preferably at room temperature.

The subsequent hydrolysis is preferably carried out either in the presence of an acid such as hydrochloric acid, sulphuric acid, phosphoric acid, trichloroacetic acid or trifluoroacetic acid, in the presence of a base such as sodium hydroxide or potassium hydroxide in an appropriate solvent such as water, water/methanol, ethanol, water/ethanol, water/isopropanol or water/dioxane at temperatures between -10°C and 120°C, e.g. between room temperature and the boiling point of the reaction mixture.

In the above translations, if necessary, existing reactive groups such as hydroxy, amino or alkylamine groups may be protected during translation by usual protective groups which are then decomposed after translation.

For example, the trimethylsilyl, acetyl, benzoyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group may be used as a preservative for a hydroxy group and the acetyl, benzoyl, ethoxycarbonyl or benzyl group may be used as a preservative for an amino, alkylamino or imino group.

The subsequent separation of a residue used as a preservative, if any, is preferably by hydrolysis in an aqueous solvent, e.g. water, isopropanol/water, tetrahydrofuran/water or dioxan/water, in the presence of an acid such as hydrochloric acid or sulphuric acid or in the presence of an alkali base such as sodium hydroxide or potassium hydroxide, if any, at temperatures between 0 and 100 °C, preferably at the boiling point of the reaction mixture. However, the separation of a benzene ring is preferably by hydrolysis, e.g. with hydrogen in the presence of a catalyst such as palladium/carbon in a solvent, ethanol, hydrogen peroxide or, if necessary, an additive such as methacrylic acid, at a room temperature between 0 and 7 °C, but preferably at a pressure of between 1 and 3 bar but not less than 50 °C, preferably at a room temperature between 0 and 7 °C.

The resulting mixture of isomers of a compound of general formula I may preferably be chromatographically separated using a carrier such as silica gel or aluminium oxide.

Furthermore, the resulting compounds of general formula I may be converted into their salts of acid addition, particularly for pharmaceutical use, into their salts which are physiologically compatible with inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, fumaric acid, amber acid, lactic acid, citric acid, tartaric acid or maleic acid.

In addition, the new compounds of generic formula I thus obtained, if they contain a carboxy or lH-tetrazolyl group, may be subsequently converted, if desired, into their salts with inorganic or organic bases, in particular for pharmaceutical use, into their physiologically compatible salts, such as sodium hydroxide, potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of general formulae II to XI used as starting materials are partly known from the literature or obtained by known methods.

For example, a compound of general formula II is obtained by alkylation of a corresponding o-amino nitrate compound and subsequent reduction of the nitrogroups.

A compound of general formulae III, V, VI, VII, IX or X used as a starting material is obtained by acylation of a corresponding o-phenylenediamine or o-amino nitrate compound, then reduction of the nitrogruppe and subsequent cycling of an o-diaminophenyl compound obtained and subsequent cleavage of a residue used, or, where appropriate, by cycling of a correspondingly substituted benzimidazole with a corresponding amine or by NH alkylation of a corresponding lH-benzimidazole, the isomeric composition thus obtained being subsequently separated by usual methods, e.g. chromatography.

For example, 2-n-propyl-5-imidazo[1,2-a]pyridine-2-yl) - 3H benzimidazole is obtained by conversion of p-aminoacetophenone with butyric acid chloride, subsequent nitration, bromination, ring closure with 2-aminopyridine to the 6-n-butanoylamido-3-imidazo[1,2-a]pyridine-2-yl) nitrobenzol, which is then transferred to the desired compound by cyclization after reduction of the nitrogruppe, or

2-n-propyl-4-methyl-6- ((1-methylbenzimidazole-2-yl) -H-benzimidazole by nitration of 3-methyl-4-n-butanoylamide benzoic acid methyl ester, subsequent reduction of the nitrogroup and cycling to 2-n-butyl-4-methyl-6-methoxycarbonyl1H-benzimidazole, which is then converted to the desired compound by cycling with 2-methylaminoaniline.

The novel compounds of generic formula I and their physiologically compatible salts have valuable pharmacological properties and are angiotensin antagonists, in particular angiotensin II antagonists.

For example, the links have been The following is the biphenyl,B =4'-[[2-n-propylbenzimidazole-2-methyl-6-yl]]-benzimidazole-1-yl-methyl]biphenyl,B =4'-[[2-n-propylbenzimidazole-2-methyl]benzimidazole-1-methyl]methyl-2-methyl,B =4'-[[2-n-propylbenzimidazole-2-methyl]]-benzimidazole-1-methyl-2-methyl,B =4'-[[1-n-propylbenzimidazole-2-methyl]]-methyl,P=4'-n-propylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-1-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methylbenzimidazole-2-methyl,P=4'-n-methyl-methyl-benzimidazole-2-methyl,P=4'-n-methyl-methyl-methyl-methyl-benzimidazole-2-methyl,P=4'-methyl-methyl-methyl-methyl-methyl-methyl-methyl,P=4'-n-methyl-methyl-methyl-methyl-methyl-methyl-methyl,P=4'-n-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl,P=4'-n-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-

The following table shows the results of the analysis of the data collected in the study:

The tissue (rat lung) is homogenised in Tris buffer (50 mMol Tris, 150 mMol NaCl, 5 mMol EDTA, pH 7.40) and centrifuged twice every 20 minutes at 20,000 x g. The final pellet is resuspended in incubation buffer (50 mMol Tris, 5 mMol MgCl2, 0.2% BSA, pH 7.40) 1:75, based on the moisture content of the tissue. Each 0,1 ml homogenate is homogenised for 60 minutes at 37°C with 50 pM [125I] angiotensin II (NEN, triglycerides, FRG) and increasing concentrations of the test substance in a total volume of 0.25 mg. The incubation is completed by rapid glass matrix filtration. The dose is determined in a filter of 4 ml TW filter, with a corresponding pH of 2.5 mg/ml, and a corresponding concentration of 0.4 mg/ml of Gamma-Cool is determined in a buffer of 0.50 mg/ml.

Substances A to K show the following IC50 values in the test described: Other

Substanz
A	3,7
B	14,0
C	1,2
D	20,0
E	12,0
F	26,0
G	3,4
H	1,2
I	1,7
J	20,0
K	7,8

In addition, compounds A, B, C, D, E and G were tested for their effects after oral administration in watchful, renally hypertensive rats using methods known in the literature and showed blood pressure lowering effects at a dose of 10 mg/ kg.

Furthermore, no toxic side effects, e.g. no negative inotropic effect and no arrhythmia, were observed when the above compounds were administered up to a dose of 30 mg/kg intravenously, and the compounds are therefore well tolerated.

Due to their pharmacological properties, the new compounds and their physiologically compatible salts are suitable for the treatment of hypertension and heart failure, as well as for the treatment of ischemic peripheral circulation disorders, myocardial ischemia (angina), the prevention of progression of heart failure after myocardial infarction, the treatment of diabetic nephropathy, glaucoma, gastrointestinal and bladder diseases.

The new compounds and their physiologically compatible salts are also suitable for the treatment of pulmonary diseases such as pulmonary edema and chronic bronchitis, the prevention of arterial re-stenosis after angioplasty, thickening of the vessel wall after vascular surgery, arteriosclerosis and diabetic angiopathy.

The dosage required to achieve the corresponding effect in adults is preferably 20 to 100 mg, preferably 30 to 70 mg, administered intravenously and 50 to 200 mg, preferably 75 to 150 mg, administered orally, 1 to 3 times daily, respectively. For this purpose, the compounds of the generic formula I as described in the invention may be used, where appropriate, in combination with other active substances such as blood pressure lowerers, diuretics and/or calcium antagonists, together with one or more inert solid carrier substances and/or diluents, e.g. cornstarch, milk sugar, cane sugar, microcellulose, polycrystalline magnesium, a capsular polyethylene, sulphuric acid, water/hydrochloric acid, water/propyl/ethyl acetate, water/hydrochloric acid, water/hydrochloric acid, water/ethyl alcohol, water/propyl/ethyl alcohol, water/ethyl alcohol, water/ethyl alcohol, water/propyl/ethyl alcohol, water/ethyl alcohol, water/ethyl alcohol, water/ethyl esters, water/ethyl alcohol, water/ethyl esters, water/ethyl esters, water/ethyl esters, water/ethyl esters, water/ethyl esters, or their substrates, or their salts.

Therefore, for the above mentioned combinations, additional active substances such as bendroflumethiazide, chlorthiazide, hydrochlorothiazide, spironolactone, benzthiazide, cyclothiazide, ethacrylic acid, furosemide, metoprolol, prazosin, atenolol, propranolol, (di) hydralazine hydrochloride, diltiazem, felodipine, nicardipin, niipin, nisoldipin and nitrendipin may be considered. e dosage of these active substances is conveniently reduced from 1/5 of the lowest dose usually recommended to 1/1 of the dose usually recommended, i. e. 15 to 200 mg hydrochlorothiazide, 125 to 200 mg propranolol, 15 to 200 mg felodipine, 15 to 200 mg niipin, 5 to 60 mg propranolol, 5 to 60 mg niipin, 5 to 80 mg propranolol, 5 to 60 mg niipin.

The following examples are intended to illustrate the invention:

Example A It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

0,7 g (1,15 mMol) 4'-[[2-n-butyl-7-[5-imidazol-1-yl) -pentyloxy]-4-methyl-benzimidazol-1-yl]-methyl]-biphenyl-2-carbonic acid-tert.butylester is dissolved in 35 ml of methyl chloride, 5 ml of trifluoric acid is added and stirred at room temperature for 12 hours. The organic phase is dried over sodium sulphate and vacuum-pressed. The resulting raw product is purified from acetone by means of a silica gel column (coronal thickness: 0,063-0,020, acetic acid/E/Amonon = 90:100,0 mm): crystallised and purified from acetone. The yield is 0.19 g (29.9% of the theory). The melting point is 185-187°C. The following is added to the list of active substances: Other

Ber.	C	71,81	H	7,09	N	9,85
Gef.		72,03		7,19		9,71

The mass spectrum: m/e = M+ 550

Example 1 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The following table shows the results of the analysis of the product characteristics of the product: The yield is 63.9% of the theory. The melting point is 261-263°C The following is added to the list of active substances: Other

Ber.	C	77,02	H	5,87	N	10,89
Gef.		76,90		5,85		10,99

Analogue to Example 1 the following compounds are obtained: The total value of all the materials of Chapter 9 used does not exceed 20% of the ex-works price of the product

Example 2 The following substances are to be classified in the same heading as the active substance:

Add 4,3 g (66 mMol) sodium biphenyl and 3,5 g (66 mMol) ammonium chloride to a solution of 1,60 g (3,3 mMol) 4'-[[2-n-propyl-4-methyl-6- ((1-methylbenzimidazole-2-yl) benzimidazole-1-yl]-methyl-2-cyanobiphenyl] in 50 ml of dimethylformamide and stir the mixture at 140 °C for 24 hours. Then add water and vacuum the precipitate. The resulting raw material is chromatographically purified with a silica gel (300 g silica gel, methylene chloride + 6% ethanol). The yield is 900 mg (51% of the theory). The melting point is 228 to 230 °C. The following shall be added to the list of active substances: Other

Ber.	C	73,58	H	5,61	N	20,80
Gef.		73,48		5,55		20,70

The following compounds are obtained by analogy Example 2:4-benzimidazole-2-yl-1-benzimidazole-2-yl-2-n-hexylbenzimidazole-1-yl-methyl-2-benzimidazole-2-yl-biphenyl-2-benzimidazole-2-methyl-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-methyl-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-methyl-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimidazole-2-benzimide-2-benzimide-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimide-2-benzimidazole-2-benzimide-2-benzimide-2-benzimide-2-benzimidazole-2-benzimide-2-benzimide-2-benzimidazole-2-benzimide-2-benzimide-2-benzimidazole-2-benzimide-2-benzimide-2-benzimidazole-2-benzimide-2-benzimide

Example 3 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-propyl-4-methyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 49.0% of the theory. The melting point: from 186°C sinter The following is added to the list of active substances: Other

Ber.	C	64,30	H	5,77	N	18,10	S	5,92
Gef.		64,10		5,39		18,01		5,98

Example 4 The following substances are to be classified in the same heading as the active substance:

Manufactured analogue example 2 from 4'-[[2-ethyl-4-methyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 60.0% of the theory. Melting point: amorphous, sintered from 194°C The following is added to the list of active substances: Other

Ber.	C	63,74	H	5,54	N	18,58	S	6,08
Gef.		63,83		5,66		18,41		5,82

Example 5 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-butyl-4-methyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 48.0% of the theory. Melting point: amorphous, sintered from 183°C The following is added to the list of active substances: Other

Ber.	C	64,84	H	5,99	N	17,64	S	5,77
Gef.		64,53		5,66		17,63		5,55

Example 6 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-propyl-4-ethyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 27.0% of the theory. Melting point: amorphous, sintered from 189°C The following is added to the list of active substances: Other

Ber.	C	64,84	H	5,99	N	17,64	S	5,77
Gef.		64,81		5,68		17,87		5,31

Example 7 The following substances are to be classified in the same heading as the active substance:

Manufactured analogue example 2 from 4'-[[2-ethyl-4-ethyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 39.0% of the theory. Melting point: amorphous, sintered from 212°C The following is added to the list of active substances: Other

Ber.	C	64,30	H	5,77	N	18,10	S	5,92
Gef.		64,30		5,51		17,99		5,59

Example 8 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-propyl-4-isopropyl-6- ((butansultam-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 22.0% of the theory. The following shall be added to the list of active substances: The following substances are to be classified in the same heading as the product: Other

Ber.	C	65,35	H	6,19	N	17,21	S	5,63
Gef.		65,13		6,10		17,54		5,40

Example 9 The following substances are to be classified in the same heading as the active substance:

Manufactured analogue example 2 from 4'-[[2-ethyl-4-isopro pyl-6- ((butansultam-1-yl) -benzimidazole -1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethyl formamide. The yield is 24.0% of the theory. Melting point: amorphous, sintered at or above 209 °C The following is added to the list of active substances: Other

Ber.	C	64,84	H	5,99	N	17,64	S	5,77
Gef.		64,99		5,71		17,43		5,71

Example 10 The following substances are to be classified in the same group as the active substance:

Analogue Example 2 produced from 4'-[[2-n-propyl-4-trifluorethyl-6-[[butansultam-1-yl]]-benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide yield: 17,0% of the theory, The melting point is 199-203°C The following shall be reported for the product concerned: Other

Ber.	C	58,48	H	4,74	N	16,46
Gef.		58,28		4,43		16,22

Example 11 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The following is added to the list of active substances in Annex I to Regulation (EC) No 1907/2006 by adding the following additional substances: The yield is 48.0% of the theory. The melting point is 233 to 235 °C. The following is added to the list of active substances: Other

Ber.	C	77,25	H	6,10	N	10,60
Gef.		77,10		5,98		10,46

Example 12 The following substances are to be classified in the same heading as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-butyl-4-methyl-6- ((1-methylbenzimidazole-2-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 41.0% of the theory. The melting point is 235-237°C The following shall be added to the list of active substances: Other

Ber.	C	73,89	H	5,84	N	20,28
Gef.		73,67		5,81		19,93

Analogue to Example 12 the following compounds are obtained: The following substances are to be classified in the same subheading as the product of the preparation of the product:

Example 13 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-propyl-4-methyl-6- ((2-oxo-piperidin-1-yl) -benzimidazole-1-yl]-methyl]-2-cyano-biphenyl and sodium azide in dimethylformamide. The yield is 51.0% of the theory. Melting point: amorphous, sintered from 140°C The following shall be reported: Other

Ber.	C	71,26	H	6,18	N	19,39
Gef.		71,08		6,22		19,47

Example 14 The following substances are to be classified in the same heading as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-butyl-4-methyl-6- ((2-oxo-piperidin-1-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 39.0% of the theory. Melting point: amorphous, sintered from 128°C The following shall be added to the list of active substances: Other

Ber.	C	71,65	H	6,40	N	18,87
Gef.		71,44		6,23		18,59

Example 15 The following substances are to be classified in the same group as the active substance:

It is obtained from 4'-[[2-n-propyl-4-methyl-6- ((2-oxo-piperidine-1-yl) -benzimidazole-1-yl]-methyl]-2- ((2-triphenylmethyl-tetrazol-5-yl) -biphenyl by cleavage of the triphenyl methyl group by methanolic hydrochloric acid. The yield is 51.0% of the theory. Melting point: amorphous, sintered from 115°C The following shall be reported: Other

Ber.	C	71,26	H	6,18	N	19,39
Gef.		71,51		6,39		19,09

Example 16 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[[2-n-propyl-4-methyl-6-]]imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl]-methyl]biphenyl-2-carbonic acid-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 38.0% of the theory. Melting point: 195-197°C (after evaporation of the solvent) The following formulae are used: The following is added to the list of active substances: Other

Ber.	C	76,78	H	5,64	N	11,19
Gef.		76,55		5,61		10,87

Example 17 The following substances are to be classified in the same category as the active substance:

Analogue Example 2 is prepared from 4'-[[2-n-propyl-4-methyl-6-]]imidazo[1,2-a]pyridin-2-yl) benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. Melting point: from 181°C sinter The following is added to the list of active substances: Other

Ber.	C	73,26	H	5,38	N	21,36
Gef.		73,10		5,24		21,13

Analogue Example 17 will obtain the following connection: The following substances are to be classified in the same category as the active substance:

Example 18 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[[2-n-butyl-4-methyl-6-]]imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl]-methyl]biphenyl-2-carbonic acid-tert.butylester and trifluoric acid in methylene chloride. The yield is 51.0% of the theory. The melting point is 194-197°C The following is added to the list of active substances: Other

Ber.	C	77,02	H	5,88	N	10,89
Gef.		76,81		5,78		10,64

Example 19 The following substances are to be classified in the same group as the active substance:

Analogue Example 2 is prepared from 4'-[[2-n-butyl-4-methyl-6-imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The following shall be added to the list of active substances: Other

Ber.	C	73,58	H	5,61	N	20,80
Gef.		73,39		5,40		20,92

Example 20 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[[2-n-propyl-4-methyl-6-]]imidazo[1,2-a]pyrimidine-2-yl) -benzimidazole-1-yl]-methyl]biphenyl-2-carbonic acid-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 47% of the theory. Melting point: 224-226°C (after evaporation of the solvent) The following formulae are used: The following is added to the list of active substances: Other

Ber.	C	74,23	H	5,43	N	13,96
Gef.		74,10		5,31		13,66

Example 21 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[[2-n-propyl-4-methyl-6-]]imidazo[2,1-b]thiazol-6-yl) -benzimidazol-1-yl]-methyl]biphenyl-2-carbonic acid-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 43 percent of the theory. Melting point: 192 to 195°C (after evaporation of the solvent) The following substances are to be classified in the same group as the product: The following is added to the list of active substances: Other

Ber.	C	71,12	H	5,17	N	11,06	S	6,33
Gef.		70,97		5,19		10,88		6,09

Example 22 The following substances are to be classified in the same category as the active substance:

The following table is prepared by analogy with the example 2 of 4'-[[2-n-propyl-4-methyl-6- ((imidazo [2,1-b]thiazol-6-yl) -benzimidazol-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The yield is 21%. Melting point: amorphous, sintered from 196°C The following shall be reported: Other

Ber.	C	67,90	H	4,94	N	21,12	S	6,04
Gef.		67,77		4,84		21,00		5,87

Example 23 The following substances are to be classified in the same group as the active substance:

Manufactured analogue example 2 from 4'-[[2-n-propyl-4-methyl-6- ((benzimidazole-2-yl) -benzimidazole-1-yl]-methyl]-2-cyanobiphenyl and sodium azide in dimethyl formamide. The yield is 28%. The following shall be added to the list of active substances: The following is added to the list of active substances: Other

Ber.	C	73,26	H	5,38	N	21,36
Gef.		73,01		5,22		21,56

Analogue to Example 23 yields the following compounds: The following substances are to be classified in the immediate vicinity of the product:

Example 24 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 43 percent of the theory. The melting point is 239-242°C. The following is added to the list of active substances: Other

Ber.	C	76,78	H	5,64	N	11,19
Gef.		76,55		5,60		11,41

Analogue to Example 24 the following compounds are obtained: The use of the active substance in the active substance shall be authorised only if the substance is incorporated in the active substance and the active substance is not used in the active substance.

Example 25 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[[2-n-butyl-6-(2,3-di-methylmaleic acid amino) -4-methyl-benz-imidazole-1-yl]-methyl]-biphenyl-2-carbonic acid-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 88.9% of the theory. The melting point is 321-322°C. The following is added to the list of active substances: Other

Ber.	C	72,43	H	6,08	N	7,92
Gef.		72,89		6,16		7,89

Example 26 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Manufactured analogue Example A from 4'-[[6-(2,3-dimethylmaleic acid amino) 2-n-propyl-4-methyl-benzimidazole-1-yl]-methyl]biphenyl-2-carbonic acid-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 75.4% of the theory. The melting point is 329-331°C The following is added to the list of active substances: Other

Ber.	C	72,08	H	5,85	N	8,13
Gef.		72,04		5,84		7,96

Example 27 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The following table shows the results of the analysis of the product characteristics of the product: The yield is 64% of the theory. The melting point is 217 to 719 °C. The following is added to the list of active substances: Other

Ber.	C	77,24	H	6,10	N	10,60
Gef.		77,12		6,09		10,75

Example 28 The following substances are to be classified in the same category as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 15% of the theory. The melting point is between 215°C and 217°C. The following shall be added to the list of active substances: Other

Ber.	C	73,89	H	5,84	N	20,28
Gef.		73,66		6,02		20,56

Example 29 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-Cyclopropyl-4-methyl-6-(1-methylbenzimidazole-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butylester and trifluoric acid in methylene chloride. The yield is 52% of the theory. The melting point is 244 to 246 °C. The following is added to the list of active substances: Other

Ber.	C	77,32	H	5,51	N	10,93
Gef.		77,75		5,71		10,94

Example 30 The substance is to be classified in the additive as a substance of heading 2913 or as a substance of heading 2913 or 2913

Analogue Example 2 is prepared from 4'-[2-Cyclopropyl-4-methyl-6-[1-methylbenzimidazole-2-yl) -benzimidazole-1-yl) -methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The melting point is 245-247°C The following is added to the list of active substances: Other

Ber.	C	73,86	H	5,26	N	20,88
Gef.		73,95		5,42		20,90

Example 31 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-Cyclobutyl-4-methyl-6-(1-methylbenzimidazole-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butylester and trifluoric acid in methylene chloride. The yield is 63% of the theory. The melting point is 189-191°C The following is added to the list of active substances: Other

Ber.	C	77,55	H	5,74	N	10,64
Gef.		77,35		5,92		10,40

Example 32 The following substances are to be classified in the same category as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 61% of the theory. The melting point is 197-199°C The following shall be added to the list of active substances: Other

Ber.	C	74,16	H	5,49	N	20,35
Gef.		74,12		5,74		20,67

Example 33 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(1-methyl-5-fluor-benzimidazole-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butyl ester and trifluorosilic acid in methylene chloride. The yield is 34% of the theory. The melting point is 250-252°C The following is added to the list of active substances: Other

Ber.	C	74,42	H	5,49	N	10,52
Gef.		74,14		5,64		10,54

Analogue Example 33 will obtain the following connection: It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Example 34 The following substances are to be classified in the same category as the active substance:

The following table is used for the analysis of the product characteristics of the product: The yield is 16.5% of the theory. The following shall be indicated in the table: The following is added to the list of active substances: Other

Ber.	C	68,49	H	5,38	N	23,19
Gef.		68,25		5,50		23,37

Analogue to Example 34 the following compounds are obtained: The following substances are to be classified in the same category as the active substance:

Example 35 The following substances are to be classified in the same group as the active substance:

Analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(5,6,7,8-tetrahydro-imidazo[1,2-a]-pyridin-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butyl ester and trifluoroacetic acid in methylene chloride. The yield is 67%. The following shall be indicated in the table: The following is added to the list of active substances: Other

Ber.	C	76,16	H	6,39	N	11,10
Gef.		75,94		6,46		11,20

Analogue Example 35 gives the following compounds: It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5 and boiling in the range of approximately -15oC to -15oC (- 100oF to -15oF).]

Example 36 The following substances are to be classified in the same category as the active substance:

The following table is used for the analysis of the following: The yield is 73.5% of the theory. The following shall be indicated in the table: The following is added to the list of active substances: Other

Ber.	C	72,70	H	6,10	N	21,20
Gef.		72,40		6,07		21,48

Analogue Example 36 gives the following compounds: The following substances are to be classified in the same category as the active substance:

Example 37 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(1-methyl-6-fluor-benzimidazole-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butyl ester and trifluorosilic acid in methylene chloride. The yield is 76 percent of the theory. The melting point is 243 to 245 °C. The following is added to the list of active substances: Other

Ber.	C	74,42	H	5,49	N	10,52
Gef.		74,74		5,52		10,77

The mass spectrum: m/e = 532

Example 38 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The following table shows the results of the analysis of the product characteristics of the product: The yield is 52.7% of the theory. The melting point is 292 to 295 °C. C32H27CN4O2 (535,06) and its salts The following information shall be provided for the purpose of the analysis: Other

Ber.	C	71,90	H	5,08	N	10,45	Cl	6,63
Gef.		71,29		5,21		10,40		6,76

Example 39 The following substances are to be classified in the same heading as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 54.8% of the theory. Melting point: from 204°C sinter The following is added to the list of substances which are to be used: The following table shows the results of the analysis of the test method: Other

Ber.	C	62,55	H	4,71	N	18,85	Cl	11,85
Gef.		62,34		4,97		18,84		11,57

Example 40 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.] (a) 3-methyl-4-butyryllamino-5-nitroacetophenone

Stir in 32,6 g (148 mMol) 3-methyl-4-butyryllaminoacetophenone in 300 ml of smoking sulphuric acid at -15 °C, in portions, and stir for another 30 minutes at -15 °C. Then stir the reaction mixture on 3 1 ice, suck the raw material out, wash with 400 ml of water, dry and clean by recrystallization from ethanol/diethyl ether (1:1). The yield is 23.8 g (61.0% of the theory). The following information shall be provided for the purpose of the assessment: The test chemical is used to determine the concentration of the test substance in the test medium.

(b) 3-methyl-4-butyryllamino-5-nitro-β-bromacetophenone, whether or not containing other oxygen functional groups

A solution of 23.8 g (90 mMol) 3-methyl-4-butyrilamino-5-nitroacetophenone in 900 ml dichloromethane is drained at room temperature by stirring a solution of 16.0 g (200 mMol) bromine in 140 ml dioxane so slowly that the reaction mixture is always completely discoloured. The mixture is then stirred for another two hours, the reaction mixture is vacuum-pressed to dry, the resulting residue is driven with approximately 20 ml dichloromethane/diethyl (1:1) and sucked and then dried. This results in 23 g (74% of the theory) 3-methyl-4-butyrilamino-5-nitroacetophenone, which contains 10% of the product. The starting material is further reduced to caesium bromide without further purification. The test chemical is used to determine the concentration of the test substance in the test medium. The test chemical is used to determine the concentration of the active substance in the test chemical.

(c) 2-butyrilamino-3-nitro-5- ((imidazole-4-yl) -toluol, whether or not chemically defined

A solution of 6.8 g (20 mMol) 3-methyl-4-butyrylamino-5-nitro-ω-bromacetophenone in 20 ml of formamide is heated to 140 °C for 2 hours. The cooled solution is then poured into about 50 ml of 1 N ammonia and stirred for about 15 minutes. The resulting raw product is sucked, washed and dried with about 50 ml of water, resulting in 4.4 g (75 per cent of the theory) of the product, which is processed without further purification. The test chemical is used to determine the concentration of the active substance in the test chemical.

(d) 2-butyrylamino-3-nitro-5- ((1-methyl imidazole-4-yl) -toluol

Add 1,3 g (9,5 mMol) of methyl iodide at room temperature to a solution of 2.5 g (8,7 mMol) 2-butyrylamino-3-nitro-5- ((imidazole-4-yl) toluol and 5.2 g (30 mMol) potassium carbonate dihydrate in 30 ml dimethyl sulfoxide and stir for 2 hours. Then stir the reaction mixture in about 150 ml of water and then extract four times with 25 ml of vinegar. Wash, dry and compress the organic extracts with about 30 ml of water. The resulting raw product is cleaned by column chromatography (300 g silica gel, solvent: methyl chloride/methanol = 30:1). The yield is 640 mg (24 per cent of the theory). The test chemical is used to determine the concentration of the active substance in the test chemical.

(e) 2-butyrilamino-3-amino-5- ((1-methyl imidazole-4-yl) -toluol, whether or not chemically defined

Hydrate 640 mg (2,1 mMol) 2-butyrylamino-3-nitro-5-(1-methyl-imidazole-4-yl) toluol in 30 ml of methanol after addition of approximately 200 mg palladium/carbon (20%) at room temperature and a hydrogen pressure of 5 bar. After complete hydrogen uptake, the catalyst filters and tightens the filtrate. The resulting raw material is further processed without further purification. The test chemical is used to determine the concentration of the test chemical in the test medium. The test chemical is used to determine the concentration of the active substance in the test chemical.

(f) 2-n-propyl-4-methyl-6- ((1-methyl-imidazole-4-yl) benzimidazole, whether or not containing other oxygen functional groups

600 mg (2,1 mMol) 2-butyrylamino-3-amino-5-(1-methyl-imidazole-4-yl) toluol is heated in 10 ml of ice vinegar for one hour to return to the surface. The residue is then evaporated in a vacuum to dry, mixed with about 15 ml of water, alkalinized with ammonia and extracted four times with about 10 ml of acetic acid. The organic extracts are washed, dried and finally compressed with about 15 ml of water. The resulting raw product is processed without further purification. The yield is 420 mg (79% of the theory). The test chemical is used to determine the concentration of the active substance in the test chemical.

(g) 4'-[2-n-propyl-4-methyl-6- ((1-methyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonic acid-tert.butyl esters

To make a solution of 200 mg (0.79 mMol) 2-n-propyl-4-methyl-6-(1-methyl-imidazole-4-yl) benzimidazole and 90 mg (0.8 mMol) potassium-tert.butylate in 5 ml dimethyl sulfoxide, give 280 mg (0.8 mMol) 4'-bromethyl-biphenyl-2-carbonate-tert.butylester and stir the mixture at room temperature for 90 minutes, then stir in about 40 ml of water, extract four times with about 10 ml of vinegar, then wash, dry and dry the organic extracts with 10 ml of water. The resulting raw product was cleaned by sacromatography (100 g g of silica, Laclean; dichloromethane = 30:1) The yield is 230 mg (56% of the theory). The test chemical is used to determine the concentration of the active substance in the test chemical.

(h) 4'-[2-n-propyl-4-methyl-6-[[1-methyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonic acid

A solution of 230 mg (0.44 mMol) 4'-[(2-n-propyl-4-methyl-6- (((2-n-methyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]biphenyl-2-carbonic acid-tert.butylester and 2 ml of trifluoric acid in 10 ml of dichloromethane was stirred overnight at room temperature and then compressed to dry. The residue was dissolved in approximately 5 ml of dilute baking soda, the solution neutralised with acetic acid, the precipitation was then sucked out, washed with water and dried. The melting point is 293 to 295 °C. The test chemical is used to determine the concentration of the active substance in the test chemical. Analogue example 40 gives the following compounds: The following substances are to be classified in the same group as the active substance:

Example 41 The following substances are to be classified in the same category as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 24%. The melting point is 255-257°C The test chemical is used to determine the concentration of the active substance in the test chemical. The following is added to the list of active substances: Other

Ber.	C	68,75	H	5,97	N	22,12
Gef.		68,90		5,97		22,03

The following compounds are obtained by analogy with Example 41:4'-[2-n-propyl-4-methyl-6- ((1-ethyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-2-(1-H-tetrazol-5-yl) -biphenyl4'-[2-n-propyl-4-methyl-6- ((1-benzyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonic acid4'-([2-n-propyl-4-methyl-6-(1-isopropyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-2-1-H-tetrazol-5-yl) -biphenyl

Example 42 The following substances are to be classified in the same category as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive: The yield is 21%. The following shall be added to the list of active substances: The test chemical is used to determine the concentration of the active substance in the test chemical. C31H30N8 (514,64) Other

Ber.	C	72,35	H	5,88	N	21,78
Gef.		72,01		5,82		21,44

Example 43 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(8-methyl-imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butyl ester and trifluorosilic acid in methylene chloride. The yield is 87 percent of the theory. The melting point is 295-297°C The test chemical is used to determine the concentration of the active substance in the test chemical. The following table shows the calculation of the CO2 savings: Other

Ber.	C	74,41	H	6,06	N	10,52
Gef.		74,81		6,05		10,43

Example 44 The following substances are to be classified in the same category as the active substance:

Manufactured analogue Example 2 from 4'-[(2-n-propyl-4-methyl-6-(2-pyridyl) -benzimidazole-1-yl) -methyl]-2-cyanobiphenyl and sodium azide in dimethyl formamide. The yield is 56% of the theory. The following shall be added to the list of active substances: The following is added to the list of active substances: Other

Ber.	C	72,85	H	5,71	N	19,83
Gef.		72,45		6,01		19,83

Example 45 The following substances are to be classified in the same category as the active substance:

Analogue Example 2 is obtained from 4'-[(2-n-propyl-4-methyl-6-(8-methyl-imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl) -methyl]-2-cyanobiphenyl and sodium azide in dimethylformamide. The following shall be added to the list of active substances: The test chemical is used to determine the concentration of the active substance in the test chemical. C33H30N8 (538,61) Other The mass spectrum: m/e = 538

Example 46 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

Analogue sample A is prepared from 4'-[2-Ethyl-4-methyl-6- ((5,6,7,8-tetrahydro-imidazo[1,2-a]pyridin-2-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butyl ester and trifluoroacetic acid in methylene chloride. The yield is 50% of the theory. The following shall be added to the list of active substances: The test chemical is used to determine the concentration of the active substance in the test chemical.

Example 47 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(1-isopropyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-biphenyl-2-carbonate-tert.butylester and trifluoroacetic acid in methylene chloride. The yield is 84% of the theory. The melting point is 285-286°C The test chemical is used to determine the concentration of the active substance in the test chemical.

Example 48 The following substances are to be classified in the same category as the active substance:

The product obtained by analogy Example 2 from 4'-[2-n-propyl-4-methyl-6- ((1-isopropyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-2-cyanobiphenyl and sodium azide in dimethyl formamide. The yield is 18%. The following shall be added to the list of active substances: The test chemical is used to determine the concentration of the active substance in the test chemical. C31H32N8 (516,66) Other The mass spectrum: m/e = 516

Example 49 It consists predominantly of hydrocarbons having carbon numbers predominantly in the range of C1 through C5.]

The analogue sample A is prepared from 4'-[(2-n-propyl-4-methyl-6-(1-benzyl-imidazole-4-yl) -benzimidazole-1-yl) -methyl]-biphenyl-tert.butylester and trifluoroacetic acid in methylene chloride.

Example 50 The following substances are to be classified in the same category as the active substance:

The following table is used for the determination of the concentration of the active substance in the feed additive:

Example 51

Ampullen, enthaltend 50 mg Wirkstoff pro 5 ml
Wirkstoff	50 mg
	2 mg
	50 mg
NaCl	12 mg
Wasser für Injektionszwecke ad	5 ml

Manufacture:

Dissolve the buffer substances and the isotonan in part of the water, add the active substance and, when fully dissolved, make up to the nominal volume with water.

Example 52

Ampullen, enthaltend 100 mg Wirkstoff pro 5 ml
Wirkstoff	100 mg
Methylglucamin	35 mg
Glykofurol	1000 mg
Polyethylenglykol-Polypropylenglykol-Blockpolymer	250 mg
Wasser für Injektionszwecke ad	5 ml

Manufacture:

Dissolve methylglucamine in part of the water and dissolve the active substance by stirring and heating.

Example 53

Tabletten, enthaltend 50 mg Wirkstoff
Wirkstoff	50,0 mg
Calciumphosphat	70,0 mg
Milchzucker	40,0 mg
Maisstärke	35,0 mg
Polyvinylpyrrolidon	3,5 ml
Magnesiumstearat	1,5 mg

Manufacture:

The active substance, CaHPO4, milk sugar and maize starch are moistened evenly with an aqueous PVP solution, the mass is passed through a 2 mm sieve, dried in the air dryer at 50 °C and re-sifted.

After mixing the lubricant, the granules are squeezed on a tablet-making machine.

Example 54

Dragees, enthaltend 50 mg Wirkstoff
Wirkstoff	50,0 mg
Lysin	25,0 mg
Milchzucker	60,0 mg
Maisstärke	34,0 mg
Gelatine	10,0 mg
Magnesiumstearat	1,0 mg

Manufacture:

The active substance is mixed with the excipients and moistened with an aqueous gelatine solution, and after screening and drying, the granules are mixed with magnesium stearate and pressed into cores.

The resulting cores are coated with a cover according to known methods.

Example 55

Dragees, enthaltend 100 mg Wirkstoff
Wirkstoff	100,0 mg
Lysin	50,0 mg
Milchzucker	86,0 mg
Maisstärke	50,0 mg
Polyvinylpyrrolidon	2,8 mg
Mikrokristalline Cellulose	60,0 mg
Magnesiumstearat	1,2 mg

Manufacture:

The active substance is mixed with the excipients and moistened with an aqueous PVP solution. The wet mass is fed through a 1.5 mm sieve and dried at 45°C. After drying, the liquid is sifted again and the magnesium stearate is added. This mixture is pressed into cores.

The resulting kernels are coated with a cover according to known methods.

Example 56

Kapseln, enthaltend 250 mg Wirkstoff
Wirkstoff	250,0 mg
Maisstärke	68,5 mg
Magnesiumstearat	1.5 mg

Manufacture:

The active substance and the corn starch are mixed and moistened with water. The wet mass is sifted and dried. The dry granules are sifted and mixed with magnesium stearate. The final mixture is filled in hard gelatin capsules size 1.

Example 57

Orale Suspension, enthaltend 50 mg Wirkstoff pro 5 ml
Wirkstoff	50,0 mg
Hydroxyethylcellulose	50,0 mg
Sorbinsäure	5,0 mg
Sorbit 70%ig	600,0 mg
Glycerin	200,0 mg
Aroma	15,0 mg
Wasser    ad	5,0 ml

Manufacture:

Distilled water is heated to 70°C. Hydroxyethyl cellulose is dissolved in it under stirring. A dose of 50 mg is contained in 5.0 ml.

Example 58

Suppositorien, enthaltend 100 mg Wirkstoff
Wirkstoff	100,0 mg
Adeps solidus	1600,0 mg

Manufacture:

The solid fat is melted, the ground active substance is dispersed homogeneously in the melt at 40°C, cooled to 38°C and poured into slightly pre-cooled suppository forms.

Claims (11)

1. Benzimidazoles of general formula wherein R₁ represents a fluorine, chlorine or bromine atom, an alkyl, cycloalkyl, fluoromethyl, difluoromethyl or trifluoromethyl group and R₂ represents a 5-, 6- or 7-membered alkyleneimino or alkenyleneimino group, optionally substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, wherein a methylene group may be replaced by a carbonyl or sulphonyl group, a maleic acid imido group optionally mono- or disubstituted by an alkyl or phenyl group, whilst the substituents may be identical or different, a benzimidazol-2-yl or 4,5,6,7-tetrahydro-benzimidazol-2-yl group optionally substituted in the 1-position by C_1-6-alkyl or a cycloalkyl group, whilst the phenyl nucleus of one of the abovementioned benzimidazole groups may additionally be substituted by a fluorine atom or by a methyl or trifluoromethyl group, R₂ may represent an imidazo[2,1-b]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-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, 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 pyridyl group or a carbon attached imidazolyl group optionally substituted in the 1-position by an alkyl or benzyl group, and which may also be substituted in the carbon skeleton by an alkyl group, R₃ represents a C_1-5-alkyl group or a C_3-5-cycloalkyl group and R₄ represents a carboxy or lH-tetrazolyl group, and the salts thereof with inorganic or organic acids or bases, whilst, unless otherwise specified, an alkyl moiety as mentioned hereinbefore may in each case contain 1 to 3 carbon atoms and a cycloalkyl moiety mentioned above may contain from 3 to 7 carbon atoms.
2. Benzimidazoles of general formula I according to claim 1, wherein R₁ represents a chlorine atom, or a C_1-3-alkyl or a trifluoromethyl group, a 5-, 6- or 7-membered alkyleneimino group wherein a methylene group is replaced by a carbonyl or sulphonyl group, a maleic acid imido group optionally mono- or disubstituted by a C_1-3-alkyl or phenyl group, whilst the substituents may be identical or different, a benzimidazol-2-yl or 4,5,6,7-tetrahydro-benzimidazol-2-yl group optionally substituted in the 1-position by a C_1-6-alkyl or by a cycloalkyl group, whilst the phenyl nucleus of one of the abovementioned benzimidazole groups may additionally be substituted by a fluorine atom or by a methyl or trifluoromethyl group, or R₂ may represent an imidazo[2,1-b]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-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, 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 pyridyl group or an imidazol-4-yl group substituted in the 1-position by a C_1-3 alkyl group or by a benzyl group which may also be substituted in the carbon skeleton by a C_1-3 alkyl group, R₃ represents a C_1-5-alkyl group or a C_3-5-cycloalkyl group and R₄ represents a carboxy or lH-tetrazolyl group, and the salts thereof with inorganic or organic acids or bases.
3. Benzimidazoles of general formula I according to claim 1, wherein R₁ represents a methyl group or a chlorine atom and R₂ represents a 5-, 6- or 7-membered alkyleneimino group, wherein a methylene group is replaced by a carbonyl or sulphonyl group, a maleic acid imido group optionally mono- or disubstituted by a C_1-3-alkyl or phenyl group, whilst the substituents may be identical or different, a benzimidazol-2-yl or 4,5,6,7-tetrahydro-benzimidazol-2-yl group optionally substituted in the 1-position by a C_1-3-alkyl group, whilst the phenyl nucleus of one of the abovementioned benzimidazole groups may additionally be substituted by a fluorine atom, or R₂ may represent an imidazo[1,2-a]-pyridin-2-yl group, 5,6,7,8-tetrahydroimidazo[1,2-a]-pyridin-2-yl, imidazo[1,2-a]pyrimidin-2-yl or imidazo [2,1-b]thiazol-6-yl group, an imidazol-4-yl group substituted in the 1-position by a C_1-3 alkyl group, R₃ represents a C_1-5-alkyl group or a C_3-5-cycloalkyl group and R₄ represents a carboxy or lH-tetrazolyl group, and the salts thereof with inorganic or organic acids or bases.
4. The following benzimidazoles of general formula I according to claim 1: (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-(butanesultam-1-yl)-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (d) 4'-[[2-n-butyl-6-(2,3-dimethylmaleic acid imino)-4-methylbenzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid, (e) 4'-[(2-cyclopropyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid, (f) 4'-[(2-n-propyl-4-methyl-6-(1-methyl-5-fluorobenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid, (g) 4'-[(2-n-propyl-4-methyl-6-(imidazo[1,2-a]pyrimidin-2-yl)-benzimidazol-1-yl)-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (h) 4'-[(2-n-propyl-4-methyl-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid, (i) 4'-[(2-n-propyl-4-methyl-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl)-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (j) 4'-[(2-n-propyl-4-chloro-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (k) 4'-[[2-n-propyl-4-methyl-6-(imidazo[2,1-b]thiazol-6-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid, (l) 4'-[[2-ethyl-4-methyl-6-(butanesultam-1-yl)-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (m) 4'-[[2-n-butyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (n) 4'-[[2-n-propyl-4-methyl-6-(imidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid, (o) 4'-[[2-n-propyl-4-methyl-6-(imidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (p) 4'-[[2-n-propyl-4-methyl-6-(imidazo[2,1-b]thiazol-6-yl)-benzimidazol-1-yl]-methyl]-2-(1H-tetrazol-5-yl)-biphenyl, (q) 4'-[(2-n-propyl-4-methyl-6-(1-methyl-6-fluorobenzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid, and (r) 4'-[(2-ethyl-4-methyl-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid, and the salts thereof with inorganic or organic acids or bases.
5. 4'-[[2-n-Propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)-benzimidazol-1-yl]-methyl]-biphenyl-2-carboxylic acid and the salts thereof with inorganic or organic acids or bases.
6. 4'-[(2-Ethyl-4-methyl-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic acid and the salts thereof with inorganic or organic acids or bases.
7. Physiologically acceptable salts of the compounds according to at least one of claims 1 to 6 with inorganic or organic acids or bases.
8. Pharmaceutical compositions containing a compound according to at least one of claims 1 to 6 or a physiologically acceptable salt according to claim 7 optionally together with one or more inert carriers and/or diluents.
9. Use of a compound according to at least one of claims 1 to 7 for preparing a pharmaceutical composition with an angiotensin-antagonist activity.
10. Process for preparing a pharmaceutical composition according to claim 8, characterised in that a compound according to at least one of claims 1 to 7 is incorporated in one or more inert carriers and/or diluents by a non-chemical method.
11. Process for preparing the benzimidazoles according to claims 1 to 7, characterised in that

    a) a compound of general formula wherein R₁ and R₂ are defined as in claims 1 to 6, one of the groups X₁ or Y₁ represents a group of general formula and the other group X₁ or Y₁ represents a group of the general formula wherein R₂ and R₄ are defined as in claims 1 to 6, R₈ represents a hydrogen atom or an R₃CO- group, wherein R₃ is defined as hereinbefore, Z₁ and Z₂, which may be identical or different, represent optionally substituted amino groups or hydroxy or mercapto groups optionally substituted by lower alkyl groups or Z₁ and Z₂ together represent an oxygen or sulphur atom, an optionally C_1-3-alkyl substituted imino group, an alkylenedioxy or alkylenedithio group, each having 2 or 3 carbon atoms, but one of the groups X₁ or Y₁ must represent a group of general formula or is cyclised and a corresponding N-oxide which might thus be obtained is reduced or

    b) a benzimidazole of general formula wherein R₁ to R₃ are defined as in claims 1 to 6, is reacted with a biphenyl compound of general formula wherein R₄ is defined as in claims 1 to 6 and Z₃ represents a nucleophilic leaving group, or

    c) in order to prepare a compound of general formula I wherein R₄ represents a carboxy group, a compound of general formula wherein R₁ to R₃ are defined as in claims 1 to 6 and R₄' represents a group which may be converted into a carboxy group by hydrolysis, thermolysis or hydrogenolysis, is converted into a corresponding carboxy compound or

    d) in order to prepare a compound of general formula I a maleic acid imido group optionally mono- or disubstituted by a C_1-3-alkyl or phenyl group, whilst the substituents may be identical or different, a benzimidazol-2-yl or 4,5,6,7-tetrahydro-benzimidazol-2-yl group optionally substituted in the 1-position by a C_1-3-alkyl group, whilst the phenyl nucleus of one of the abovementioned benzimidazole groups may additionally be substituted by a fluorine atom, or R₂ may represent an imidazo[1,2-a]-pyridin-2-yl group, 5,6,7,8-tetrahydroimidazo[1,2-a]-pyridin-2-yl, imidazo[1,2-a]pyrimidin-2-yl or imidazo[2,1-b]thiazol-6-yl group, an imidazol-4-yl group substituted in the 1-position by a C_1-3 alkyl group, R₃ represents a C_1-5-alkyl group or a C_3-5-cycloalkyl group and R₄ represents a carboxy or lH-tetrazolyl group, and the salts thereof with inorganic or organic acids or bases, particularly the physiologically acceptable salts thereof, prepared according to claim 1.

    4. The following benzimidazoles of general formula I prepared according to claim 1: (a) 4'-[[2-n-propyl-4-methyl-6-(l-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- (butanesultam-1-yl)- a compound of general formula wherein one of the groups A, B, C or D represents an optionally methyl-substituted methine group or a nitrogen atom and 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 sulphur atom, is reacted with a compound of general formula wherein R₁, R₃ and R₄ are defined as in claims 1 to 6 and Z₄ represents a nucleophilic leaving group such as a halogen atom, e.g. a chlorine or bromine atom, or

    g) in order to prepare compounds of general formula I wherein R₂ represents one of the benzimidazol-2-yl, imidazo [4,5-b]pyridin-2-yl, imidazo[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 purin-8-yl groups mentioned in claims 1 to 6, a compound of general formula wherein none, one or two of the groups A₁, B₁, C₁ or D₁ represents a nitrogen atom and the remaining groups A₁, B₁, C₁ or D₁ represent methine groups, R₁₁ represents a hydrogen or fluorine atom or a methyl or trifluoromethyl group, one of the groups X₂ or Y₂ represents an R₁₃-NH- group and the other X₂ or Y₂ group represents a group of general formula wherein R₁, R₃ and R₄ are defined as in claims 1 to 6, one of the groups R₁₃ or R₁₄ represents a hydrogen atom and the other R₁₃ or R₁₄ group represents a hydrogen atom, a C_1-6-alkyl group or a C_3-7-cycloalkyl group, Z₅ and Z₆, which may be identical or different, represent optionally substituted amino groups or hydroxy or mercapto groups optionally substituted by lower alkyl groups or Z₅ and Z₆ together represent an oxygen or sulphur atom, an optionally C_1-3-alkyl-substituted imino group, an alkylenedioxy or alkylenedithio group each having 2 or 3 carbon atoms, is cyclised and a corresponding N-oxide which might be thus obtained is reduced and a compound thus obtained is optionally subsequently hydrolysed, and if necessary a protecting group used during the reactions a) to g) in order to protect reactive groups is cleaved and/or if desired an isomer mixture thus obtained is resolved into its isomers, and/or a compound of general formula I thus obtained is converted into a salt thereof, more particularly for pharmaceutical use a physiologically acceptable salt thereof with an inorganic or organic acid or base.