DE4142366A1 - New phenylalkyl derivs. - are angiotensin II antagonists used to treat hypertension, coronary insufficiency, angina, cns disorders etc. - Google Patents

Abstract

Phenylalkyl derivs. of formula (I), and their isomer mixts. enantiomers, tautomers and salts, are new. In (I) n = 0 or 1; A = alkylene; B = O, C(O), CH(OH), S, SO, SO2, alkylene, 2-4C alkylidene, 1,1-cycloalkylene, or NH (opt. substd. by alkyl or 1-4C alkenoyl); Ra = Cl, Br, OH, RSO2O, PhSO2O, PhQSO2O or one of 10 N-contg. heterocyclic gps. defined in the specification. Rb = (a) CN, COOH, CF3CONH, CF3CONHCH2, CF3SO2NH, CF3SO2NHMe, RSO2NH, RSO2NHCH2, etc., or (b) 1H-tetrazolyl, 1H-tetrazolylalkyl, 1H-tetrazolylaminocarbonyl or triazole, all opt. substd. by R, CF3, PhQ or Ph3C; or (C) 1-6C alkyl sulphonylaminocarbonyl (opt. perfluoroinated in alkyl), 2-7C alkoxycarbonyl, aralkoxycarbonyl, pivaloyloxymethoxycarbonyl, phthalidylmethoxycarbonyl, ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl, cyclohexylcarbonylmethoxycarbonyl or (1,3-dioxa-2-oxo- 4-methyl-cyclopenten-5-yl)-methoxycarbonyl; Rc = H, R, ArQ, Ar, COOH or COCO; Rd = 1-10C alkyl; 2-10C alkenyl, 2-10C alkynyl, cycloalkyl, cycloalkylalkyl, phenyl (opt. mono- or disubstd. by F, Cl, Br, Me or MeO), biphenylyl, naphthyl or heteroaryl; Re, Rf = H, or Re, Rf may also be F, Cl, Br, R or RO; Q = 1-4C alkylene; R = 1-4C alkyl; cycloalkyl contains 3-7C; Aryl = phenyl (mono- or disubstd. by F, Cl, Br, OH, R, RO, PhQO, Ph, NO2, NH2, RNH, (R)2N, alkanoylamine, CN, COOH, ROCO, NH2CO, RNHCO, (R)2NCO, CF3, alkanoyl, NH2SO2, RNHSO2 or (R)2NSO2) or naphthyl; Heteroaryl = a 5-membered heteroaromatic ring (contg. (i) and NH, O or S gp.; (ii) NH and O, S or N, or (iii) NH and 2 or 3 N) or a 6-membered heteroaromatic ring (contg. 1-3N atoms), both opt. mono- or disubstd. by F, Cl, Br, R, RO, OH, Ph, NO2, NH2,RNH, (R)2N, alkanoylamine, CN, COOH, ROCO, NH2CO, RNHCO, (R)2NCO, CF3, alkanoyl, NH2SO2, RNHSO2 or (R)2NSO2; Ph = phenyl. USE - (I) Are angiotensin antagonists, esp. angiotensin II antagonists, useful in treatment of hypertension, coronary insufficiencies, ischaemic peripheral circulation disorders, angina, prevention of insufficiency following myocardial infarction, treatment of diabetic nephropathy, glaucoma, gastrointestinal disorders and bladder infections. (I) Are also useful in treatment of pulmonary disorders (e.g., lung oedema and bronchitis) prevention of arterial restenosis, and treatment of arteriosclerosis and diabetic angiopathy. They are also useful in treatment of depression, Alzheimer's disease, Parkinsons's disease, Bulimia and disorders of cognitive functions. Admin.is intravenous, in doses of 20-100 (esp. 30-70) mg/day, or oral, in doses of 50-200 (esp. 75-150)mg/day.

Description

The present invention relates to phenylalkyl derivatives the general formula

and the compound 5,7-dimethyl-2-ethyl-3- [4- [α- (1H-tetrazole- 5-yl) benzyloxy] -3,5-dichlorobenzyl] imidazo [4,5-b] pyridine, their mixtures of isomers, their tautomers, their enantiomers and their salts, in particular for pharmaceutical use their physiologically compatible salts with inorganic or organic acids or bases.

In the general formula above means
n is the number 0 or 1,
A is a straight-chain or branched alkylene group,
B is an oxygen atom, a carbonyl, hydroxymethylene, sulfenyl, sulfinyl or sulfonyl group, a straight-chain or branched alkylene group, an alkylidene group with 2 to 4 carbon atoms, a 1,1-cycloalkylene group or optionally with an alkyl group or with an alkanoyl group 1 to 4 carbon atoms substituted imino group,
R _{a is} a chlorine or bromine atom, a hydroxyl, alkylsulfonyloxy, phenylsulfonyloxy or phenylalkylsulfonyloxy group or a group of the formula

in which
one of the radicals D₁, D₂ or D₃ is a methylene or imino group and the remaining radicals of the radicals D₁ to D₃ are each methine groups, it being possible for one methine group to be replaced by a nitrogen atom and one of the methine groups to be replaced by the radical R₅ and optionally another of the methine groups the radical R₄ can be substituted,
zero, one or two of the radicals D₄, D₅, D₆ or D₇ a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each methine groups, it being possible for one methine group to be additionally substituted by the radical R₄ and a further methine group to be substituted by the radical R₅,
E is a carbon-carbon bond, an oxygen or sulfur atom, a hydroxymethylene or carbonyl group or one optionally by an alkyl group having 1 to 6 carbon atoms, by a cycloalkyl group, by an alkanoyl group having 2 to 5 carbon atoms, by an allyl or phenyl imino group substituted by benzyl group,
X represents an oxygen or sulfur atom or an imino group optionally substituted by an alkyl, phenyl or phenylalkyl group,
R₁ is a straight-chain or branched alkyl group having 1 to 9 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, the abovementioned saturated and unsaturated alkyl parts each being represented by a cycloalkyl group, by a fluorine, chlorine or bromine atom, can be substituted by a hydroxy, amino, alkylamino, dialkylamino or α, α-difluoroethane group, a perfluoroalkyl group having 1 to 4 carbon atoms or a cycloalkyl group which can be mono- or disubstituted by a trifluoromethyl group or an alkyl group,
R₂ is a hydrogen, fluorine, chlorine or bromine atom, an alkyl or perfluoroalkyl group each having 1 to 5 carbon atoms, a cyano or nitro group,
R₃ is a hydrogen atom, a cyano group, an alkyl group with 1 to 6 carbon atoms optionally substituted by a hydroxy or alkoxy group, a perfluoroalkyl group with 1 to 6 carbon atoms, an alkenyl group with 3 to 6 carbon atoms optionally substituted by fluorine atoms, a phenylalkyl or phenylalkenyl group with 2 up to 4 carbon atoms in the alkenyl part, an alkyl group with 1 to 5 carbon atoms, which are terminated by an imidazol-1-yl, triazolyl, tetrazolyl, phthalimido-, Ro-COO-, R-S-, R₇SO-, R₇SO₂-, R₇CO-, R₇NHCOO -, R₇NHCO, R₇NHCONR₇, R₈CONR₇ or R₈SO₂NR₇ group is substituted, wherein
the triazolyl group can additionally be mono- or disubstituted with an acetoxy or alkyl group and
R₆ is an alkyl or perfluoroalkyl group each having 1 to 8 carbon atoms, a cycloalkyl, phenyl, benzyl, phenylethyl, adamantyl, naphthyl, naphthylmethyl or naphthylethyl group,
R₇ has a hydrogen atom and the meanings mentioned above for R₆,
R₈ has the meanings mentioned above for R₇ and represents a piperazino group which is optionally substituted in the 4-position by an alkyl or phenyl group, a pyrrolidino, piperidino, hexamethyleneimino, morpholino, R₇O or (R₇) ₂N group,
R₄ is a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl group, a cycloalkyl group, an alkyl group substituted by 1, optionally substituted by a cycloalkyl group, by a hydroxy, alkoxy, alkylamino, dialkylamino, alkoxycarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group up to 6 carbon atoms and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl or perfluoroalkyl group each having 1 to 6 carbon atoms, an alkenyl or alkynyl group each having 2 to 6 carbon atoms, the above-mentioned alkyl and alkenyl parts each being substituted by a heteroaryl, hydroxyl, alkoxy, amino, Alkylamino, dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, piperidinocarbonyl, morpholinocarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, tetrazol-5-yl-5-tetra -yl-aminocarbonyl, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylaminocarbonyl, heteroarylaminosulfonyl or alkylcarbonylaminosulfonyl group may be mono- or disubstituted
an alkoxy group having 1 to 7 carbon atoms which is substituted in the 2-, 3-, 4-, 5-, 6- or 7-position by an imidazolyl, tetrazolyl, benzimidazolyl or tetrahydrobenzimidazolyl group, or a phenylalkoxy group,
an alkylsulfonyloxy group with 1 to 4 carbon atoms, a benzenesulfonyloxy or phenylalkanesulfonyloxy group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, in which the acyl radical is an alkanoyl group having 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, the above-mentioned phenyl nuclei each being represented by a fluorine, chlorine or bromine atom , mono- or disubstituted by a methyl or methoxy group and the substituents can be the same or different,
a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, where a carbonyl group in a phthalimino group can be replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group can be substituted by one or two alkyl groups , and additionally the phenyl nuclei mentioned above are mono- or disubstituted by alkyl or alkoxy groups, where the substituents can be the same or different and, at the same time, can be fully or partially hydrogenated,
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, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a bicycloalkane-2,3-dicarboxylic acid imino or bicycloalkene-2,3-dicarboxylic acid imino group in which the bicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms, can be substituted by 1, 2 or 3 methyl groups and an endomethylene group can be replaced by an oxygen atom,
a glutaric acid imino group in which the n-propylene group can be perfluorinated, can be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group,
a maleimide group optionally mono- or disubstituted by an alkyl or phenyl group, where the substituents can be identical or different,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms or by a cycloalkyl group,
a pyrrolidine, piperidine or pyridine ring bonded via a carbon atom, where a phenyl radical is fused to the pyridine ring via two adjacent carbon atoms and a methylene group adjacent to the N atom in a pyrrolidine or piperidine ring can be replaced by a carbonyl group,
an imidazolidinedione group optionally substituted by an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group,
a pyridazin-3-one or dihydro-pyridazin-3-one group which can be substituted in the 2-position by an alkyl group optionally substituted by a phenyl group and in the carbon skeleton additionally by 1 or 2 alkyl groups, or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 8 carbon atoms or phenylalkyl group,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 8 carbon atoms, an alkenyl group with 3 to 5 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
one of the radicals R₉, R₁₀ or R₁₁ also a bicyclohexyl or biphenylyl group or
R₁₀ and R₁₁ together with the intermediate nitrogen atom, a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group or
R₉ and R₁₁ together represent an alkylene group with 2 to 4 carbon atoms,
R _b is cyano, carboxy, Trifluormethylcarbonylamino-, Trifluormethylcarbonylaminomethyl-, Trifluormethylsulfonylamino-, Trifluormethylsulfonylaminomethyl-, alkylsulfonylamino, Alkylsulfonylaminomethyl-, arylsulfonylamino, Arylsulfonylaminomethyl-, Aralkylsulfonylamino-, Aralkylsulfonylaminomethyl-, Arylsulfonylaminocarbonyl-, Benzylsulfonylaminocarbonyl-, sulfo, aminosulphonyl , alkylaminosulfonyl, Aralkylaminosulfonyl-, Arylaminosulfonyl-, Alkylcarbonylaminosulfonyl-, Aralkylcarbonylaminosulfonyl-, Arylcarbonylaminosulfonyl-, sulfomethyl, Aminosulfonylmethyl-, Alkylaminosulfonylmethyl-, Aralkylaminosulfonylaminomethyl-, Arylaminosulfonylmethyl-, Alkylcarbonylaminosulfonylmethyl-, Aralkylcarbonylaminosulfonylmethyl-, Arylcarbonylaminosulfonylmethyl-, phosphino, O-alkyl phosphino-, O-aralkyl-phosphino-, O-aryl-phosphino-, phosphono-, O-alkyl-phosphono-, O-aralkylphosphono-, O-aryl-phosphono-, O, O-dialkylphosphono-, phosphonomethyl- , O-alkyl-phosphono-methyl, O-aralkyl-phospho no-methyl-, O-aryl-phosphono-methyl-, O, O-dialkylphosphonomethyl-, phosphato-, O-alkyl-phosphato-, O-aralkyl-phosphato-, O-aryl-phosphato- or O, O-dialkoxy -phosphoryl group, a 1H-tetrazolyl, 1H-tetrazolylalkyl, 1H-tetrazolylaminocarbonyl or triazolyl group, optionally substituted by an alkyl, trifluoromethyl, phenylalkyl or triphenylmethyl group, an alkylsulfonylaminocarbonyl or perfluoroalkylsulfonylamino group with a 1-bis-alkylsulfonylamine group, a 1-bis-bisphenylamino group with a 1-bis-alkylsulfonylamino group Alkoxycarbonyl group with a total of 2 to 7 carbon atoms, an aralkoxycarbonyl group, a pivaloyloxymethoxycarbonyl, phthalidylmethoxycarbonyl, ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl, cyclohexyloxycarbonylmethoxycarbonyl or (1,3-dioxa-2-oxo-4-methylcarbonyl) cyclopentene group ;
R _{c is} a hydrogen atom, an alkyl, aralkyl, aryl, carboxy or alkoxycarbonyl group,
R _{d is} a straight-chain or branched alkyl chain having 1 to 10 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 10 carbon atoms, a cycloalkyl or cycloalkylalkyl group, one optionally by fluorine, chlorine or bromine atom, by methyl or methoxy groups mono- or disubstituted phenyl group, a biphenyl, naphthyl or heteroaryl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, a carbonyl group in a phthalimino group being replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group being substituted by one or two alkyl groups can, and in addition the above-mentioned phenyl nuclei mono- or disubstituted by alkyl or alkoxy groups, where the substituents can be the same or different and at the same time can be completely or partially hydrogenated,
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, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a bicycloalkane-2,3-dicarboxylic acid imino or bicycloalkene-2,3-dicarboxylic acid imino group in which the bicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms, can be substituted by 1, 2 or 3 methyl groups and an endomethylene group can be replaced by an oxygen atom,
a glutaric acid imino group in which the n-propylene group can be perfluorinated, can be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group,
a maleimide group optionally mono- or disubstituted by an alkyl or phenyl group, where the substituents can be identical or different,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms or by a cycloalkyl group, or
a pyrrolidine, piperidine or pyridine ring bonded via a carbon atom, where a phenyl radical is fused to the pyridine ring via two adjacent carbon atoms and a methylene group adjacent to the N atom in a pyrrolidine or piperidine ring can be replaced by a carbonyl group,
an imidazolidinedione group optionally substituted by an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group,
a pyridazin-3-one or dihydro-pyridazin-3-one group which can be substituted in the 2-position by an alkyl group optionally substituted by a phenyl group and in the carbon skeleton additionally by 1 or 2 alkyl groups, or
represents a R₁₁-NR₁₀-CO-NR₉ group in which R₉, R₁₀ and R₁₁ are as defined above,
also fluorine, chlorine or bromine atoms, alkyl or alkoxy groups,
in particular those compounds in which R _a to R _f , A, B and n are defined with the proviso that
D₄ to D₇ with the additional provisions (a) to (j) represent methine groups or
D₇ represents a nitrogen atom and the radicals D₄, D₅ and D₆ with the additional provisos (a) to (g) and (k) to (m) or (a) to (g) and (n) to (p) methine groups or
one of the residues D₄, D₅ or D₆ represents a nitrogen atom and the remaining residues of the residues D₄ to D₆ and D₇ represent methine groups or
two of the residues D₄ to D₇ represent nitrogen atoms and the remaining residues of the residues D₄ to D₇ represent methine groups,
with the additional proviso that either

• (a) n represents the number 1 or
• (b) E with the exception of the carbon-carbon bond for E has the meanings mentioned above or
• (c) A with the exception of the methylene group that for A above has the meanings mentioned or
• (d) B except for the oxygen atom is the same as for B above has the meanings mentioned or
• (e) R _b, with the exception of the carboxyl group, has the meanings mentioned above for R _b or
• (f) R _c, with the exception of the hydrogen atom, has the meanings mentioned above for R _c or
• (g) R _d, with the exception of the phenyl group, has the meanings mentioned above for R _d or
• (h) R₁ except for the n-butyl group for R₁ has the meanings mentioned above or
• (i) R₄ with the exception of the methyl group in position 7 which for R₄ has the meanings mentioned above or
• (j) R₅ with the exception of the hydrogen atom for R die has the meanings mentioned above, or that
• (k) R₁ except for the ethyl group for R₁ has the meanings mentioned above or
• (l) R₄ with the exception of the methyl group in position 7 which for R₄ has the meanings mentioned above or
• (m) R₅ with the exception of the methyl group in position 5 which for R₅ has the meanings mentioned above or
• (n) R₁ except for the n-propyl group for R₁ above has the meanings mentioned or
• (o) R₄ with the exception of the hydrogen atom which is for R₄ has the meanings mentioned above or
• (p) R₅ with the exception of the hydrogen atom for R für has the meanings mentioned above and

the remaining radicals have the meanings mentioned above,
where in addition one methine group mentioned in the abovementioned definitions of the radicals D₄ to D₇ can be substituted by the radical R₄ and another methine group mentioned in the abovementioned definition of the radicals D₄ to D₇ by the radical R₅,
unless otherwise mentioned,
the alkyl, alkylene or alkoxy parts mentioned above can each contain 1 to 4 carbon atoms and the cycloalkyl parts can each contain 3 to 7 carbon atoms, and
under "an aryl group" one optionally by a fluorine, chlorine or bromine atom, by a hydroxy, alkyl, alkoxy, phenylalkoxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano -, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group, mono- or disubstituted phenyl group, where the alkyl part can each contain 1 to 4 carbon atoms, or one and
under "a heteroaryl group" a 5-membered heteroaromatic ring which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or an imino group and 2 or 3 nitrogen atoms, and a 6-membered heteroaromatic ring which 1, Contains 2 or 3 nitrogen atoms, the rings mentioned above additionally by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino , Cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group can be understood to be mono- or disubstituted.

The new compounds of the general formula I above, in which R _{a represents} a chlorine or bromine atom, a hydroxyl, alkylsulfonyloxy, phenylsulfonyloxy or phenylalkylsulfonyloxy group, are valuable intermediates and the other compounds of the above general formula I and their physiologically tolerable salts have valuable pharmacological properties since these are angiotensin antagonists, in particular angiotensin II antagonists.

The present invention thus relates to the new Phenylalkyl derivatives mentioned above, the corresponding O-substituted phosphono or phosphato compounds as well as the corresponding cyano, alkoxycarbonyl or Triphenylmethyl compounds also valuable intermediates represent.

Another object of the present invention are thus new drugs which are one of the pharmacologically mentioned above active compounds of general formula I or a corresponding physiologically compatible addition salt included and especially for the treatment of hypertension and Heart failure, also for the treatment of peripheral ischemic Circulatory disorders, myocardial ischemia (angina), for the prevention of heart failure progression after myocardial Infarction, to treat diabetic nephropathy, glaucoma, gastrointestinal and bladder disorders are suitable.

For those defined by the residues D₄, D₅, D₆ and D₇ the heteroaromatic radicals mentioned at the beginning comes the pyrido, Pyrimido, pyrazino or pyridazino group, which in Carbon skeleton substituted by the radicals R₄ and R₅ can be considered.

Preferred compounds of the above general formula I are with the ecxeption of

• (i) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (ii) 2-n-propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine and
• (iii) 5,7-dimethyl-2-ethyl-3- [4 - [(α-carboxy) benzyloxy] - benzyl] imidazo [4,5-b] pyridine

those in which
n is the number 0 or 1,
A is a straight-chain or branched alkylene group,
B is an oxygen atom, a straight-chain or branched alkylene group having 1 to 3 carbon atoms or an imino group optionally substituted by an alkyl group or by an alkanoyl group having 1 to 4 carbon atoms,
R _{a is} a group of the formula

in which
zero, one or two of the radicals D₄, D₅, D₆ or D₇ a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each methine groups, it being possible for one methine group to be additionally substituted by the radical R₄ and a further methine group to be substituted by the radical R₅,
E is a carbon-carbon bond, an oxygen or sulfur atom or an imino group which is optionally substituted by an alkyl group having 1 to 4 carbon atoms,
X is an oxygen or sulfur atom,
R₁ is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, the abovementioned saturated and unsaturated alkyl parts each being represented by a fluorine, chlorine or bromine atom, by a hydroxy or amino group, or a cycloalkyl group with 3 to 6 carbon atoms,
R₂ is a hydrogen, fluorine, chlorine or bromine atom, an alkyl or perfluoroalkyl group each having 1 to 5 carbon atoms, a cyano or nitro group,
R₃ is a hydrogen atom, a cyano group, an alkyl group with 1 to 3 carbon atoms optionally substituted by a hydroxy or alkoxy group, a perfluoroalkyl group with 1 to 3 carbon atoms, an alkenyl group with 3 to 6 carbon atoms optionally substituted by fluorine atoms, an alkyl group with 1 to 3 carbon atoms which is terminally substituted by an R₆COO, R₇S, R₇SO, R₇SO₂, R₇CO, R₇NHCOO, R₇NHCO, R₇NHCONR₇, R₈CONR₇ or R₈SO₂NR₇ group, where
R₆ is an alkyl or perfluoroalkyl group each having 1 to 4 carbon atoms, a cycloalkyl, phenyl, benzyl or phenylethyl group,
R₇ has a hydrogen atom and the meanings mentioned above for R₆,
R₈ has the meanings mentioned above for R₇,
R₄ is a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl group, a cycloalkyl group, an alkyl group which has 1 to 6 carbon atoms and is optionally substituted by a hydroxyl, alkoxy or alkoxycarbonyl group and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl or perfluoroalkyl group each having 1 to 6 carbon atoms, an alkenyl or alkynyl group each having 2 to 6 carbon atoms, the above-mentioned alkyl and alkenyl parts each being substituted by a heteroaryl, hydroxyl, alkoxy, amino, Alkylamino, dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or tetrazol-5-yl group can be mono- or disubstituted
an alkoxy group with 1 to 5 carbon atoms,
an alkylsulfonyloxy group with 1 to 4 carbon atoms, a benzenesulfonyloxy or phenylalkanesulfonyloxy group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, in which the acyl radical is an alkanoyl group having 1 to 5 carbon atoms, an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, one Alkylsulfonyl group having 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, the phenyl nuclei mentioned above each being mono- or disubstituted by a fluorine, chlorine or bromine atom, by a methyl or methoxy group and the substituents can be the same or different,
a phthalimino or homophthalimino group, it being possible for a carbonyl group in a phthalimino group to be replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group to be substituted by one or two alkyl groups, and in addition the phenyl nuclei mentioned above by alkyl or Alkoxy groups mono- or disubstituted, where the substituents can be the same or different and at the same time can be completely or partially hydrogenated,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, Alkylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group monosubstituted or by fluorine or chlorine atoms, by methyl, methoxy groups may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms, or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 6 carbon atoms or phenylalkyl group,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 6 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
R₁₀ and R₁₁ together with the intermediate nitrogen atoms are a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group or
R₉ and R₁₁ together represent an alkylene group with 2 to 4 carbon atoms,
R _{b is} a cyano-, carboxy-, arylsulfonylaminocarbonyl-, benzylsulfonylaminocarbonyl-, sulfo-, alkylcarbonylaminosulfonyl-, aralkylcarbonylaminosulfonyl-, arylcarbonylaminosulfonyl-, alkylcarbonylaminosulfonylmethyl-, aralkylcarbonylaminosulfonylmethyl-, arylcarbonyl, methyl-, phosphonylmethyl-, arylcarbonyl- -Alkyl-phosphono, O, O-dialkylphosphono-, phosphono-methyl, O-alkyl-phosphonomethyl, O, O-dialkylphosphono-methyl, phosphato or O-alkylphosphato group, optionally by a phenylalkyl - 1H-tetrazolyl or 1H-tetrazolylalkyl group substituted by triphenylmethyl, an alkylsulfonylaminocarbonyl or perfluoroalkylsulfonylaminocarbonyl group each having 1 to 6 carbon atoms in the alkyl part, an alkoxycarbonyl group having a total of 2 to 7 carbon atoms or an aralkoxycarbonyl group,
R _{c is} a hydrogen atom, a methyl, phenyl, benzyl, carboxy or alkoxycarbonyl group and
R _{d is} a straight-chain or branched alkyl chain having 1 to 6 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, a cycloalkyl or cycloalkylalkyl group, one optionally by fluorine, chlorine or bromine atom, by methyl or Methoxy groups mono- or disubstituted phenyl group, a biphenyl, naphthyl or heteroaryl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a phthalimino or homophthalimino group, where a carbonyl group in a phthalimino group can be replaced by a methylene, alkylmethylene or dialkylmethylene group, and a methylene group in a homophthalimino group can be substituted by one or two alkyl groups, and in addition the above-mentioned phenyl nucleus by alkyl - or alkoxy groups mono- or disubstituted, where the substituents can be the same or different and at the same time can be completely or partially hydrogenated,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups are replaced by N atoms n can, in addition to the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy can be disubstituted and optionally substituted in an imidazole ring NH group by an alkyl group having 1 to 6 carbon atoms, or
a R₁₁-NR₁₀-CO-NR₉ group in which R9 to R₁₁ are defined as mentioned above,
also mean chlorine or bromine atoms, methyl or methoxy groups,
unless otherwise mentioned,
the alkyl, alkylene or alkoxy parts mentioned above can each contain 1 to 4 carbon atoms and the cycloalkyl parts can each contain 3 to 7 carbon atoms, and
"aryl group" means a phenyl group which is mono- or disubstituted, optionally by a fluorine, chlorine or bromine atom, by a hydroxyl, alkyl, alkoxy, phenylalkoxy, phenyl or nitro group, the alkyl part each containing 1 to 4 carbon atoms can, or a naphthyl group and
under "a heteroaryl group" a 5-membered heteroaromatic ring which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or an imino group and 2 or 3 nitrogen atoms, and a 6-membered heteroaromatic ring which 1, Contains 2 or 3 nitrogen atoms, where the rings mentioned above can additionally be understood to be mono- or disubstituted by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl or nitro group,
their mixtures of isomers, their tautomers, their enantiomers and their salts.

Particularly preferred compounds of the above general Formula I are with the exception of

• (i) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (ii) 2-n-propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine and
• (iii) 5,7-dimethyl-2-ethyl-3- [4 - [(α-carboxy) benzyloxy] - benzyl] imidazo [4,5-b] pyridine

those in which
n is the number 0,
A is a methylene, ethylene or ethylidene group,
B an oxygen atom, a methylene, imino, methylimino or acetylimino group,
R _{a is} a group of the formula

in which
zero, one or two of the radicals D₄, D₅, D₆ or D₇ a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each methine groups, it being possible for one methine group to be substituted by the radical R₄ and another methine group to be substituted by the radical R₅,
E is a carbon-carbon bond,
R₁ is a straight-chain or branched alkyl group having 1 to 6 carbon atoms,
R₂ is a hydrogen, fluorine, chlorine or bromine atom,
R₃ is a hydroxyalkyl group with 1 or 2 carbon atoms,
R₄ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl group with 1 to 3 carbon atoms,
an amino or nitro group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 5 carbon atoms, in which the acyl radical represents an alkanoyl group having 1 to 5 carbon atoms or a benzenesulfonyl group, the phenyl nucleus mentioned above being mono- or disubstituted by a methyl or methoxy group and the substituents being the same or can be different,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two methyl groups, in which a methylene group can be replaced by a carbonyl or sulfonyl group, or a phthalimino, homophthalimino or isoindolin-1-one-yl group,
a benzimidazol-2-yl group which is optionally substituted in the 1-position by an alkyl group having 1 to 3 carbon atoms or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 5 carbon atoms or a phenylalkyl group with 1 to 3 carbon atoms in the alkyl part,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 5 carbon atoms or a cyclohexyl group,
R₁₁ is a hydrogen atom, a benzyl group or an alkyl group having 1 to 5 carbon atoms or
R₉ and R₁₁ together represent an alkylene group with 2 or 3 carbon atoms,
R _{b is} a carboxy, 1H-tetrazolyl or O-alkylphosphono- or alkylsulfonylaminocarbonyl group, each having 1 to 3 carbon atoms in the alkyl part,
R _{c is} a hydrogen atom or a phenyl group,
R _{d is} a straight-chain or branched alkyl chain with 1 to 4 carbon atoms, a cyclohexyl, cyclohexylmethyl, phenyl, biphenyl, methoxyphenyl, chlorophenyl, pyridyl or naphthyl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a benzimidazol-2-yl group which is optionally substituted in the 1-position by an alkyl group having 1 to 3 carbon atoms,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two methyl groups, in which a methylene group can be replaced by a carbonyl or sulfonyl group, or
a R₁₁-NR₁₀-CO-NR₉ group in which R₉ to R₁₁ are defined as mentioned above,
also mean methoxy groups, chlorine or bromine atoms, their isomer mixtures, their tautomers, their enantiomers and their salts.

According to the invention, the compounds of the general Formula I according to the following methods:

a) implementation of a compound of the general formula

R _a -H (II)

in which R _{a is} as defined at the outset, with a compound of the general formula

in which A, B, n and R _c to R _{f are} as defined at the outset and Z₁ is a nucleophilic leaving group such as a halogen atom, e.g. B. a chlorine, bromine or iodine atom, or a substituted sulfonyloxy group, e.g. B. represents a methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy group, and subsequent hydrolysis if necessary.

The reaction is advantageously carried out in a solvent or solvent mixture such as methylene chloride, diethyl ether, Tetrahydrofuran, dioxane, dimethyl sulfoxide, dimethylformamide or benzene, optionally in the presence of an acid-binding Agents such as sodium carbonate, potassium carbonate, sodium hydroxide, Potassium tert-butoxide, triethylamine or pyridine, where the latter two also used as solvents at the same time can be, preferably at temperatures between 0 and 100 ° C, e.g. B. at temperatures between room temperature and 50 ° C.

The subsequent hydrolysis is conveniently either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, Trichloroacetic acid or trifluoroacetic acid or in the presence of a base such as sodium hydroxide or potassium hydroxide in a suitable solvent such as water, water / Methanol, ethanol, water / ethanol, water / isopropanol or Water / dioxane at temperatures between -10 ° C and 120 ° C, e.g. B. at temperatures between room temperature and the boiling temperature of the reaction mixture.

A mixture of possible mixtures is preferably obtained during the reaction Regio isomers, which if desired subsequently, preferably chromatographically using a support such as silica gel or aluminum oxide, in the corresponding isomers is separated.

b) reaction of a compound of the general formula

in the
R _a , R _e , R _f and A are as defined in the introduction,
B 'is a straight-chain or branched alkylene group having 1 to 4 carbon atoms and
Z₂ is a nucleophilic leaving group such as a halogen atom, e.g. B. a chlorine, bromine or iodine atom or a substituted sulfonyloxy group, e.g. B. is a methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy group, with a compound of the general formula

R _b , R _d and n are defined as above and
R _c 'represents an alkoxycarbonyl group, if necessary subsequent hydrolysis and / or decarboxylation.

The reaction is advantageously carried out in a solvent or solvent mixture such as methylene chloride, diethyl ether, Tet 99999 00070 552 001000280000000200012000285919988800040 0002004142366 00004 99880rahydrofuran, dioxane, dimethyl sulfoxide, dimethylformamide or benzene, optionally in the presence of an acid-binding Agents such as sodium carbonate, potassium carbonate, sodium hydroxide, Potassium tert-butoxide, triethylamine or pyridine, where the latter two ver at the same time as a solvent can be used, preferably at temperatures between 0 and 100 ° C, e.g. B. at temperatures between room temperature and 50 ° C.

The subsequent hydrolysis is conveniently either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphorus acid, trichloroacetic acid or trifluoroacetic acid or in the presence of a base such as sodium hydroxide or potassium hydroxide in a suitable solvent such as water, water / methanol, Ethanol, water / ethanol, water / isopropanol or Water / dioxane at temperatures between -10 ° C and 120 ° C, e.g. B. at temperatures between room temperature and the boil temperature of the reaction mixture.

The subsequent decarboxylation is conveniently carried out in Presence of an acid such as hydrochloric acid, sulfuric acid, phosphorus acid, acetic acid, trichloroacetic acid or trifluoroacetic acid in a suitable solvent such as water, water / methanol, Ethanol, water / ethanol, water / isopropanol or water / dioxane at temperatures between 50 ° C and 120 ° C, e.g. B. at Temperatures between 60 ° C and the boiling point of the reaction mixture, performed.

c) For the preparation of compounds of the general formula I in which B represents an oxygen or sulfur atom or an imino group which may be substituted by an alkyl group:
Implementation of a compound of the general formula

in the
R _a , R _e , R _f and A are defined as above and
B ″ represents an oxygen or sulfur atom or an imino group optionally substituted by an alkyl group, with a compound of the general formula

in the
R _b to R _d and n are defined as above and
Z₃ is a nucleophilic leaving group such as a halogen atom, e.g. B. a chlorine, bromine or iodine atom, or a substituted sulfonyloxy group, e.g. B. a methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy group means, and if necessary subsequent hydrolysis.

The reaction is advantageously carried out in a solvent or solvent mixture such as methylene chloride, diethyl ether, Tetrahydrofuran, dioxane, dimethyl sulfoxide, dimethylformamide or benzene, optionally in the presence of an acid-binding Agents such as sodium acetate, sodium carbonate, potassium carbonate, Sodium hydroxide, potassium tert-butoxide, triethylamine or pyridine, the latter two also being solutions can be used, preferably at temperatures between 0 and 100 ° C, e.g. B. at temperatures between Room temperature and the boiling temperature of the reaction mixture, carried out.

The subsequent hydrolysis is conveniently either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphorus acid, trichloroacetic acid or trifluoroacetic acid or in the presence of a base such as sodium hydroxide or potassium hydroxide in a suitable solvent such as water, water / Methanol, ethanol, water / ethanol, water / isopropanol or Water / dioxane at temperatures between -10 ° C and 120 ° C, e.g. B. at temperatures between room temperature and the boiling temperature of the reaction mixture.

d) For the preparation of a compound of the general formula I in which R _{b represents} a carboxy group:
Conversion of a compound of the general formula

in the
R _a , R _c to R _f , A, B and n are defined as above and
R _b 'represents a groups which can be converted into a carboxy group by means of hydrolysis, thermolysis or hydrogenolysis.

For example, functional derivatives of the carboxy group such as their unsubstituted or substituted amides, esters, thiolesters, orthoesters, imino ethers, amidines or anhydrides, the nitrile group or the tetrazolyl group can be hydrolysed into a carboxy group,
Esters with tertiary alcohols, e.g. B. the tert. Butyl ester, by means of thermolysis into a carboxy group and
Esters with aralkanols, e.g. B. the benzyl ester, can be converted into a carboxy group by hydro genolysis.

The hydrolysis is advantageously carried out either in the presence an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, tri chloroacetic acid or trifluoroacetic acid or in the presence a base such as sodium hydroxide or potassium hydroxide in one suitable solvents such as water, water / methanol, ethanol, Water / ethanol, water / isopropanol or water / dioxane at temperatures between -10 ° C and 120 ° C, e.g. B. at temperatures between room temperature and the boiling point of Reaction mixture carried out. In the presence of hydrolysis an organic acid such as trichloroacetic acid or Trifluoroacetic acid may be alcoholic Hydroxy groups simultaneously in a corresponding Acyloxy group as the trifluoroacetoxy group are converted.

If R _b 'in a compound of the general formula VIII is a cyano or aminocarbonyl group, these groups can also be mixed with a nitrite, e.g. As sodium nitrite, in the presence of an acid such as sulfuric acid, which is advantageously used at the same time as a solvent, at temperatures between 0 and 50 ° C in the carboxy group leads over.

R _b 'in a compound of general formula VIII means, for example, the tert. Butyloxycarbonylgruppe, the tert. Butyl group also thermally optionally in an inert solvent such as methylene chloride, chloroform, benzene, toluene, tetrahydrofuran or dioxane and preferably in the presence of a catalytic amount of an acid such as trifluoroacetic acid, p-toluenesulfonic acid, sulfuric acid, phosphoric acid or polyphosphoric acid, preferably at the boiling point of the solvent used, e.g. B. at temperatures between 40 ° C and 100 ° C, split off.

R _b 'in a compound of general formula VIII means, for example, the tert. Butyloxycarbonylgruppe, the benzyl group can also hydrogenolytically in the presence of a hydrogenation catalyst and palladium / carbon in a suitable solvent such as methanol, ethanol, ethanol / water, glacial acetic acid, ethyl acetate, dioxane or dimethylformamide before preferably at temperatures between 0 and 50 ° C., Z . B. at room temperature, and a hydrogen pressure of 1 to 5 bar. In hydrogenolysis, other residues, e.g. B. a nitro group to the amino group, a benzyloxy group to the hydroxy group, a vinylidene group to the corresponding alkylidene group or a cinnamic acid group to the corresponding phenyl-propionic acid group, also reduced or by hydrogen atoms, for. B. a halogen atom can be replaced by a hydrogen atom.

e) To prepare a compound of the general formula I in which R _{b represents} a 1H-tetrazolyl group:
Splitting off a protective residue from a compound of the general formula

in the
R _a , R _c to R _f , A, B and n are defined as above and
R _b ″ represents a 1H-tetrazolyl group protected in the 1- or 2-position by a protective radical.

The protective residue is, for example, triphenylmethyl, Tributyltin or triphenyltin group into consideration.

A protective residue used is split off before preferably in the presence of a hydrogen halide, preferably wise in the presence of hydrogen chloride, in the presence of a Base like sodium hydroxide or alcoholic ammonia in one suitable solvents such as methylene chloride, methanol, Me thanol / ammonia, ethanol or isopropanol at temperatures between 0 and 100 ° C, but preferably at room temperature, or also, if the reaction in the presence of alcoholic Ammonia is carried out at elevated temperatures, e.g. B. at temperatures between 100 and 150 ° C, preferably at Temperatures between 120 and 140 ° C.

f) For the preparation of a compound of the general formula I in which R _{b represents} a 1H-tetrazolyl group:
Implementation of a compound of the general formula

in which R _a , R _c to R _f , A, B and n are as defined in the introduction, with hydrochloric acid or its salts.

The reaction is preferably carried out in a solvent such as Benzene, toluene or dimethylformamide at temperatures between 80 and 150 ° C, preferably at 125 ° C, performed. It is expedient to use either hydrochloric acid during the reaction from an alkali azide, e.g. B. from sodium azide, in the presence of a weak acid such as Am monium chloride released or in the reaction mixture the reaction with a salt of hydrochloric acid preferably with aluminum azide or tribuyltin azide, which also expediently in the reaction mixture by reaction of aluminum chloride or tributyltin chloride with an alkali azide such as sodium azide can be obtained Then tetrazolide salt by acidification with a dilute acid such as 2N hydrochloric acid or 2N sulfuric acid free set.

g) For the preparation of compounds of general formula I in which R _{a is} a group of the formula

represents:
Cyclization of a compound of the general formula

in the
D₁ to D₇ are as defined in the introduction,
one of the radicals X₁ or Y₁ is a group of the general formula

and the other of the radicals X₁ or Y₁ is a group of the general formula

represent where
R₁, A, B, E, n and R _b to R _{f are} as defined above,
Z₄ and Z₅, which may be the same or different, optionally substituted amino groups or optionally substituted by lower alkyl groups hydroxy or Mer capto groups or
Z₄ and Z₅, together represent an oxygen or sulfur atom, an imino group optionally substituted by an alkyl group having 1 to 3 carbon atoms, an alkylenedioxy or alkylene dithio group each having 2 to 3 carbon atoms.

The cyclization is conveniently carried out in a solvent or mixed solvents such as ethanol, isopropanol, ice vinegar, benzene, chlorobenzene, toluene, xylene, glycol, glycolmo nomethyl ether, diethylene glycol dimethyl ether, sulfolane, di methylformamide, tetralin or in an excess of Preparation of the compound of general formula XI used Acylating agent, e.g. B. 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, if appropriate in the presence of a condensing agent such as phosphorus oxychloride, thionyl chloride, sulfuryl chloride, sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, phosphorus acid, polyphosphoric acid, acetic anhydride or given if also in the presence of a base such as potassium ethylate or potassium tert.butylate. The cyclization can but also without solvents and / or condensing agents be performed.

However, the reaction is particularly advantageously carried out in such a way that a compound of the general formula XI in the reaction mixture by reduction of a corresponding o-nitro-amino compound, optionally in the presence of a carboxylic acid of the general formula R _a -E-COOH or by acylation of a corresponding o- Diamino compound is made. If the reduction of the nitro group on the hydroxylamine stage is terminated, the N-oxide of a compound of the general formula I is obtained in the subsequent cyclization. The N-oxide obtained in this way is then converted into a corresponding compound of the general formula I by reduction.

The subsequent reduction of the N-oxide of the formula obtained I is preferably in a solvent such as water, water / ethanol, Methanol, glacial acetic acid, ethyl acetate or Dimethylformamide with hydrogen in the presence of a hydrie tion catalyst such as Raney nickel, platinum or palladium / carbon, with metals such as iron, tin or zinc in the presence an acid such as acetic acid, hydrochloric acid or sulfuric acid Salts such as iron (II) sulfate, tin (II) chloride or sodium dithionite, or with hydrazine in the presence of Raney nickel Temperatures between 0 and 50 ° C, but preferably at Room temperature.

h) For the preparation of compounds of the general formula I in which R₅ represents an R₁₁-NR₁₀-CO-NR₉ group:
Implementation of a compound of the formula

in the
R _b to R _f , A, B and n are as defined in the introduction and
R _a 'represents one of the radicals mentioned for R _a , in which R₅ represents an amino group, an alkylamino group having 1 to 8 carbon atoms or a phenylalkylamino group having 1 to 4 carbon atoms in the alkyl part, with a compound of the formula

in the
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 8 carbon atoms, an alkenyl group with 3 to 5 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
one of the radicals R₁₀ or R₁₁ is also a bicyclohexyl or biphenylyl group or
R₁₀ and R₁₁ together with the intermediate nitrogen atom, a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group and
Z₆ is a nucleophilic leaving group such as a chlorine or bromine atom or also if one of the radicals R₁₀ or R₁₁ represents a hydrogen atom,
Z₆ together with R₁₀ or R₁₁ represent a nitrogen-carbon bond.

The reaction is preferably carried out in a solvent such as Given tetrahydrofuran, dioxane, ethylene chloride or benzene if in the presence of an acid-binding agent such as tri ethylamine or pyridine conveniently at temperatures between 0 and 100 ° C, preferably at temperatures between 20 and 80 ° C carried out.

i) For the preparation of compounds of the general formula I in which R₅ is an acylamino group which is optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, in which the acyl radical is an alkanoyl group with 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group with 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl or phenyl alkanoyl or Cycloalkylalkanoyl group, where the above-mentioned phenyl nuclei are each mono- or disubstituted by a fluorine, chlorine or bromine atom, by a methyl or methoxy group and the substituents can be identical or different:
Acylation of a compound of the formula

in the
R _b to R _f , A, B and n are as defined in the introduction and
R _a ″ represents one of the radicals mentioned at the outset for R _a , in which R gegebenenfalls represents an amino group optionally substituted by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, with a compound of the formula

HO-U-R₁₂ (XV)

in the
U is a carbonyl or sulfonyl group and
R₁₂ is an alkyl group with 1 to 6 carbon atoms, an alkoxy group with 1 to 3 carbon atoms, a phenyl, phenylalkyl, naphthyl or cycloalkyl group or, if U represents a carbonyl group, is a hydrogen atom, the phenyl nuclei mentioned above in each case by a fluorine -, Chlorine or bromine, mono- or disubstituted by a methyl or methoxy group and the substituents can be the same or different, or with their reactive derivatives such as their acid halides, acid esters or acid anhydrides.

As reactive derivatives of a compound of formula XV come, for example, their esters such as methyl, ethyl or benzyl esters, the thioesters such as the methylthio or Ethyl thioesters, their halides like the acid chloride, their Anhydrides or imidazolides.

The reaction is advantageously carried out in a solvent or solvent mixture such as water, methylene chloride, chloroform, Ether, tetrahydrofuran, dioxane or dimethylformamide with an appropriate carboxylic acid in the presence of a Acid activating or dehydrating agents such as thio nyl chloride, with their anhydrides such as acetic anhydride, with their esters such as ethyl acetate, with their halides such as acetyl chloride or methanesulfonyl chloride if necessary in the presence of an inorganic or tertiary organic Base such as sodium hydroxide, potassium carbonate, triethylamine or Pyridine, the latter two also being used simultaneously Solvents can be used at temperatures between -25 and 100 ° C, but preferably at temperatures between -10 and 80 ° C.

j) For the preparation of compounds of the general formula I in which R _{b represents} a phosphono- or O-alkylphosphono group:
Hydrolysis of a compound of the general formula

in the
A, B, R _a , R _c to R _f and n are defined as above and
R _b '''represents an O-alkyl or O, O-dialkyl-phosphono group in which the alkyl part can each contain 1 to 5 carbon atoms.

The reaction is preferably carried out in a solvent such as Methanol, methanol / water, ethanol or isopropanol position of a corresponding O-alkylphosphono compound general formula I in the presence of a base such as potassium hy hydroxide or potassium methylate or for the preparation of an ent speaking phosphono compound of general formula I in Presence of an acid such as hydrobromic acid at the boil temperature of the reaction mixture.

A phosphono compound of general formula I becomes special advantageous by implementing an appropriate O-alkyl or O, O-dialkyl compound of the general formula XVI with bromine / trimethylchlorosilane in acetonitrile and subsequent Hydrolysis carried out using water at room temperature.

If, according to the invention, a compound of the general formula I is obtained in which R₂ or R₅ represents a nitro group, this can be converted by reduction into a corresponding compound of the general formula I in which R₂ and R₅ represents an amino group or
If, according to the invention, a compound of the general formula I is obtained in which B represents an imino group, this can be converted by means of alkanoylation into a corresponding compound of the general formula I in which B represents an imino group substituted by an alkanoyl group having 1 to 4 carbon atoms, or
If, according to the invention, a compound of the general formula I is obtained in which B represents an imino group, this can be converted by alkylation into a corresponding compound of the general formula I in which B represents an imino group substituted by an alkyl group having 1 to 3 carbon atoms.

The subsequent reduction of the nitro group is preferred in a solvent such as water, water / ethanol, methanol, Use glacial acetic acid, ethyl acetate or dimethylformamide moderately with hydrogen in the presence of a hydrogenation catalyst with Raney nickel, platinum or palladium / carbon, with metals such as iron, tin or zinc in the presence of a Acid, with salts such as iron (II) sulfate, tin (II) chloride, sodium sulfide, sodium hydrogen sulfite or sodium dithionite, or with hydrazine in the presence of Raney nickel at temperatures between 0 and 80 ° C, but preferably at temperatures between 20 and 40 ° C, carried out.

The subsequent alkanoylation is conveniently carried out in a solvent or solvent mixture such as water, Methylene chloride, chloroform, ether, tetrahydrofuran, dioxane or dimethylformamide with a corresponding carboxylic acid in the presence of an acid activating or dehydrating agent pulling agents such as thionyl chloride, with their anhydrides such as acetic anhydride, with their esters such as ethyl acetate esters, with their halides such as acetyl chloride, if appropriate in the presence of an inorganic or tertiary organic Base such as sodium hydroxide, potassium carbonate, triethylamine or Pyridine, the latter two also being used simultaneously Solvents can be used at temperatures between -25 and 100 ° C, but preferably at temperatures between -10 and 80 ° C.

The subsequent alkylation is advantageously carried out in one Solvents or solvent mixtures such as methylene chloride, Diethyl ether, tetrahydrofuran, dioxane, dimethyl sulfoxide, di methylformamide or benzene optionally in the presence of a acid-binding agents, such as sodium carbonate, potassium carbonate, Sodium hydroxide, potassium tert-butoxide, triethylamine or pyridine, the latter two also being solutions agents can be used with an alkylating agent such as methyl iodide, ethyl iodide, isopropyl bromide, dimethyl sulfate, diethyl sulfate or p-toluenesulfonic acid methyl ester preferably at temperatures between 0 and 100 ° C, e.g. B. at Temperatures between room temperature and 50 ° C, carried out.

In the reactions described above, where appropriate existing reactive groups such as hydroxy, amino or alkylamino groups during the reaction by conventional Protection groups are protected, which after the implementation be split off again.

For example, comes as a protective residue for a hydroxy group the trimethylsilyl, acetyl, benzoyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group and as Protective residue for an amino, alkylamino or imino group Acetyl, benzoyl, ethoxycarbonyl or benzyl group into consideration.

The subsequent subsequent splitting off of one used Protective residue is preferably hydrolytically in one aqueous solvents, e.g. B. in water, isopropanol / water, Tetrahydrofuran / water or dioxane / water, in the presence of a Acid such as hydrochloric acid or sulfuric acid or in the presence an alkali base such as sodium hydroxide or potassium hydroxide Temperatures between 0 and 100 ° C, preferably at the boil temperature of the reaction mixture. The split off of a However, benzyl radical is preferably carried out by hydrogenolysis, e.g. B. with hydrogen in the presence of a catalyst such as Palladium / carbon in a solvent such as methanol, ethanol, Ethyl acetate or glacial acetic acid, optionally with addition an acid such as hydrochloric acid at temperatures between 0 and 50 ° C, but preferably at room temperature, and one Hydrogen pressure from 1 to 7 bar, but preferably from 3 up to 5 bar.

A mixture of isomers of a compound of the general If desired, formula I can preferably be chromatographic using a carrier such as silica gel or Alumina can be separated.

Furthermore, the compounds of general Formula I in its salts, especially for pharmaceutical Use in their physiologically acceptable salts with inorganic or organic acids. For example, hydrochloric acid, Hydrobromic acid, sulfuric acid, phosphoric acid, fumar acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid into consideration.

In addition, the new compounds of general formula I, if this is a carboxy or 1H-Te contain trazolyl group, if desired subsequently in their salts with inorganic or organic bases, in particular for pharmaceutical use in their physiological compatible addition salts. As bases come here, for example, sodium hydroxide, potassium hydroxide, Cyclohexylamine, ethanolamine, diethanolamine and triethanolamine into consideration.

The compounds of the general used as starting materials Formulas II to XVI are known from the literature or in part these are obtained by methods known from the literature.

For example, substituted pyrimidines are general Formula II in EP-A 04 24 317, substituted pyrimidinones in EP-A 04 07 342 and EP-A 04 19 048 Triazoles in EP-A 04 09 332, substituted triazo linones, triazolthiones and triazolimines in EP-A 04 12 594. substituted pyrazoles in EP-A 04 11 507, substituted Quinazolinones in EP-A 04 11 766, substituted quinolines in EP-A 04 12 848, five-membered condensed imidazo derivatives in EP-A 04 07 102, Benzimidazole in the EP-A 03 92 317, imidazopyridines and purines in the EP-A 04 00 974 and EP-A 03 99 731 and substituted imidazoles described in EP-A 02 53 310.

The compounds of the general used as starting materials Formulas III and IV are obtained by implementing an ent speaking alcohol with hydrogen halide, with tetrabrom methane / triphenylphosphine or with an appropriate sulfone acid halide.

The compounds of the general used as starting materials Formula VIII, IX, X, XII, XIV and XVI are obtained by Alkylation of a corresponding compound with a a compound of the general formula III analog compound.

The new compounds of general formula I and their physiologically acceptable addition salts have valuable pharmacological properties. You put angiotensin Antagonists, especially angiotensin II antagonists.

For example, the connections

A = 2-n-propyl-4-methyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
B = 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-dime thylaminocarbonylamino-benzimidazole,
C = 2-n-propyl-6- (1-methyl-benzimidazol-2-yl) -4-methyl-1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole,
D = 2-methyl-4- [4 ′ - [(α-carboxy) benzyloxy] benzyloxy] quinoline,
E = 2-n-butyl-8-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] quinazolin-4-one semihydrate,
F = 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole,
G = 2-n-butyl-6- (N-propionyl-methylamino) -1- [4 - [(1-carboxy-3-methyl) butyloxy] benzyl] benzimidazole,
H = 2-n-butyl-5-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinon-1-yl) -3- [4- [α- ( 1H-tetrazol-5-yl) benzyloxy] benzyl] imidazole [4,5-b] pyridine and
I = 2-n-butyl-1- [4 - [(α- (α-ethylphosphono) benzylamino] benzyl] benzimidazole

examined for their biological effects as follows:

Description of the method Angiotensin II receptor binding

The tissue (rat lung) is homogenized in Tris buffer (50 mmol Tris, 150 mmol NaCl, 5 mmol EDTA, pH 7.40) and centrifuged twice at 20,000 × g for 20 min each. The final pellet is resuspended in incubation buffer (50 mmol Tris, 5 mmol MgCl₂, 0.2% BSA, pH 7.40) based on the wet weight of the tissue. Each 0.1 ml homogenate is incubated for 60 min at 37 ° C. with 50 pM [125 ^I ] -angiotensin II (NEN, Dreieich, FRG) and increasing concentrations of the test substance in a total volume of 0.25 ml. The incubation is ended by rapid filtration through glass fiber filter mats. The filters are washed with 4 ml ice-cold buffer (25 mmol Tris, 2.5 mmol MgCl₂, 0.1% BSA, pH 7.40). The bound radioactivity is determined in a gamma counter. The corresponding IC ₅₀ value is determined from the dose-response curve.

The substances A to I show in the test described following IC₅₀ values:

substance IC₅₀ [nM] A 76 B 8th C. 4th D 2000 E 2000 F 12 G 830 H 27th I. 560

Furthermore, when applying the above ver bindings up to a dose of 30 mg / kg IV no toxic Side effects, e.g. B. no negative inotropic effect and no arrhythmia are observed. The Ver bonds are therefore well tolerated.

Due to their pharmacological properties, are suitable the new compounds and their physiologically tolerable Additive salts to treat hypertension and heart failure efficiency, also for the treatment of ischemic peripheral diarrhea bleeding disorders, myocardial ischemia (angina) Prevention of heart failure progression after myocardial infarction, for the treatment of diabetic nephropathy, the Glaucoma, gastrointestinal diseases and bladder diseases.

The new compounds and their physiological properties are also suitable compatible addition salts for the treatment of pulmonary Diseases, e.g. B. pulmonary edema and chronic Bronchitis, for the prevention of arterial re-stenosis, after angioplasty, from thickening of the vessel wall to vessel operations, arteriosclerosis and diabetic angiopathy. Due to the influence of acetylcholine and Diotamine release by angiotensin in the brain are suitable the new angiotensin antagonists are also central to treatment nervous disorders, e.g. B. from depression, Alzheimer's Disease, Parkinson's syndrome, bulimia, as well of disorders of cognitive functions.

The necessary to achieve a corresponding effect Dosage is expediently 20 when administered intravenously to 100 mg, preferably 30 to 70 mg, and when administered orally 50 to 200 mg, preferably 75 to 150 mg, each one to three times a day. For this purpose, according to the invention provided compounds of general formula I, given if in combination with other active substances, such as. B. Antihypertensives, diuretics and / or calcium channel blockers with one or more inert customary carriers and / or diluents, e.g. B. with cornstarch, milk sugar, Cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, Water / ethanol, water / glycerin, water / sorbitol, water / Polyethylene glycol, propylene glycol, cetylstearyl alcohol, carb oxymethyl cellulose or fatty substances such as hard fat or their suitable mixtures, in conventional pharmaceutical accessories Horse riding like tablets, drages, capsules, powders, suspensions or incorporate suppositories.

For the combinations mentioned above come as more Active substances for example bendroflumethiazide, chlorine thiazide, hydrochlorothiazide, spironolactone, benzthiazide, Cyc lothiazide, ethacric acid, furosemide, metoprolol, prazosin, Atenolol, propranolol, (di) hydralazine hydrochloride, diltiazem, Felodipine, Nicardipine, Nifedipine, Nisoldipine and Ni trendipin into consideration. The dose for these active substances is expediently 1/5 of the usually recommended lowest dosage up to 1/1 of the normally recommended dosage, for example 15 to 200 mg Hy drochlorthiazid, 125 to 2000 mg chlorthiazid, 15 to 200 mg Ethacric acid, 5 to 80 mg furosemide, 20 to 480 mg propra nolol, 5 to 60 mg felodipine, 5 to 60 mg nifedipine or 5 up to 60 mg nitrendipine.

The following examples are intended to explain the invention in more detail:

Example A 4- (α-ethoxycarbonyl-benzyloxy) benzyl bromide a) Ethyl 2-bromo-phenylacetate

43.0 g (0.2 mol) of DL-2-bromo-phenylacetic acid are dissolved in 400 ml of ethanol at room temperature with stirring. 11.8 g (0.2 mol) of thionyl chloride are slowly added dropwise at 5-10 ° C. while cooling with ice. After 12 hours at room temperature, the solvent is distilled off and the residue is taken up in ethyl acetate. After extraction with saturated sodium bicarbonate solution and with saturated saline, it is dried over sodium sulfate and concentrated.
Yield: 41.85 g (86% of theory),
R _f value: 0.60 (silica gel; mobile phase: ethyl acetate / petroleum ether = 1:19)

b) 4- (α-ethoxycarbonyl-benzyloxy) benzyl alcohol

41.8 g (0.172 mol) of 2-bromo-phenylacetic acid and 21.3 g (0.172 mol) of 4-hydroxybenzyl alcohol are dissolved in 850 ml of acetone and mixed with 24.8 g (0.18 mol) of potassium carbonate and 5.0 g ( 0.03 mol) of potassium iodide. The reaction mixture is heated to reflux with stirring for 60 hours. The inorganic salts are then filtered off and the residue is washed with hot acetone. The filtrate is concentrated and the residue is purified on a silica gel column (particle size: 0.063-0.02 mm), using initially petroleum ether, then mixtures of petroleum ether and ethyl acetate with increasing polarity (9: 1, 8: 2 and 7: 3 ) be used. The uniform fractions are concentrated in vacuo.
Yield: 30.65 g (62.5% of theory),
R _f value: 0.40 (silica gel; mobile phase: ethyl acetate / petroleum ether = 3: 7)

c) 4- (α-ethoxycarbonyl-benzyloxy) benzyl bromide

28.6 g (0.1 mol) of 4- (α-ethoxycarbonyl-benzyloxy) benzyl alcohol are dissolved in 300 ml of dichloromethane and 31.6 g (0.12 mol) of triphenylphosphine are added. A solution of 40.0 g (0.12 mol) of carbon tetrabromide in 100 ml of dichloromethane is added dropwise with ice cooling. The mixture is stirred at room temperature for 30 minutes and then concentrated. The residue is purified over a silica gel (particle size: 0.063-0.02 mm), initially using petroleum ether, then mixtures of petroleum ether and ethyl acetate with increasing polarity (9: 1 and 8: 2) as the eluent. The uniform fractions are concentrated in vacuo.
Yield: 20.45 g (59% of theory),
Oil, R _f value: 0.70 (silica gel; eluent: ethyl acetate / petroleum ether = 1: 4)
C₁₇H₁₆BrO₃ (349.24)
Calc .: C 58.20 H 4.95 Br 22.80
Found: C 58.23 H 4.84 Br 23.12

example 1 2-n-propyl-4-methyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benz imidazole a) 2-n-Propyl-4-methyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole

350 mg (2.0 mmol) of 2-n-propyl-4-methylbenzimidazole (prepared analogously to Chemistry of Heterocyclic Compounds, Vol. 40, Part 1) are added to a solution of 220 mg of potassium tert-butoxide in 30 ml of dimethyl sulfoxide , 6-12) added. After 30 minutes at room temperature, a solution of 700 mg (2.0 mmol) of 4- (α-ethoxycarbonyl-benzyloxy) benzyl bromide in 5 ml of dimethyl sulfoxide is added dropwise. After 12 hours at room temperature, the reaction solution is stirred into ice water and extracted 3 × with 100 ml of ethyl acetate. The combined organic phases are washed with 100 ml of brine and dried over sodium sulfate. After the solvent has been stripped off, the residue is purified on a silica gel column (particle size: 0.063-0.02 mm), initially using methylene chloride as the eluent, then mixtures of methylene chloride and ethanol with increasing polarity (50: 1 and 25: 1). The uniform fractions are concentrated in vacuo.
Yield: 500 mg (55% of theory),
Oil, R _f value: 0.55 (silica gel; eluent: methylene chloride / methanol = 19: 1)

b) 2-n-propyl-4-methyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] - benzimidazole

500 mg (1.1 mmol) of 2-n-propyl-4-methyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole are dissolved in 10 ml of ethanol and mixed with 10 ml of 1N sodium hydroxide solution. The mixture is stirred at room temperature for 30 minutes. The mixture is then concentrated and taken up in water. The solution is acidified by adding glacial acetic acid. The resulting precipitate is filtered off, washed neutral with water and dried. The crude product is taken up in methylene chloride and purified over a silica gel column (particle size: 0.063-0.02 mm), a mixture of methylene chloride and methanol (19: 1) being used as the eluent. The uniform fractions are concentrated in vacuo, the residue is triturated with hexane / ether and suction filtered.
Yield: 60 mg (13% of theory),
Melting point: amorphous
C₂₆H₂₆N₂O₃ (414.51)
Mass spectrum: (M + H) ⁺ = 415

Example 2 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-propionylamino- benzimidazole hydrochloride a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] -6- nitro-benzimidazole and 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] -5- nitro-benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-5-nitro-benz imidazole (produced analogously to Chemistry of Heterocyclic Compounds, Vol. 40, Part 1, 6-12) and 4 - [(α-ethoxycarbonyl) benzyloxy] benzyl bromide.
Yield: 70.5% of theory,
Oil, R _f value: 0.25 (silica gel; eluent: methylene chloride / ethanol = 50: 1)

b) 2-n-butyl-6-amino-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole

Prepared by catalytic hydrogenation of 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] -5 / 6-nitro-benzimidazole in the presence of Raney nickel in ethanol at 50 ° C under 5 bar hydrogen pressure and subsequent chromatographic separation of the 5-amino-2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole.
Yield: 21.8% of theory,
Oil, R _f value: 0.30 (silica gel; eluent: petroleum ether / methylene chloride / ethanol = 7: 2: 1)

c) 2-n-Butyl-6-propionylamino-1- [4 - [(α-ethoxycarbonyl) benz yloxy] benzyl] benzimidazole

Made from 2-n-butyl-6-amino-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and propionyl chloride / pyridine.
Yield: 70.2% of theory,
Melting point: 207-209 ° C

d) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-propionylamino- benzimidazole hydrochloride

Prepared analogously to Example 1b from 4 ′ - [(2-n-butyl-6-propion ylamino-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimide azole and 1 N sodium hydroxide solution in ethanol.
Yield: 43.5% of theory,
Melting point: sinters from 93 ° C
C₂₉H₃₁N₃O₄ × HCl (522.67)
Calculated: C 66.50 H 6.12 N 8.08
Found: C 66.73 H 6.34 N 7.81

Example 3 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-dimethyl- aminocarbonylamino-benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-carb ethoxy) benzyloxy] benzyl] -6-dimethylaminocarbonylamino-benz imidazole and 2 N sodium hydroxide solution in ethanol.
Yield: 80% of theory,
Melting point: 183-185 ° C
C₂₉H₃₂N₄O₄ (500.60)
Calc .: C 69.59 H 6.44 N 11.19
Found: C 69.54 H 6.43 N 10.66

Example 4 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-cyclohexyl aminocarbonylamino-benzimidazole hydrochloride a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl-6- cyclohexylaminocarbonyamino-benzimidazole

Made from 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyl oxy] benzyl] -6-amino-benzimidazole and cyclohexyl isocyanate / triethylamine in tetrahydrofuran.
Yield: 65.4% of theory,
Oil, R _f value: 0.40 (silica gel; eluent: methylene chloride / ethanol = 19: 1)

b) 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-cyclo hexylaminocarbonylamino-benzimidazole hydrochloride

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -6-cyclohexylaminocarbonylamino-benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 40.7% of theory,
Melting point: sinters from 184 ° C
C₃₃H₃₈N₄O₄ × HCl (591.17)
Calc .: C 67.00 H 6.60 N 9.45
Found: C 67.15 H 6.71 N 9.30

Example 5 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -5-cyclohexyl aminocarbonylamino-benzimidazole hydrochloride

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -5-cyclohexylaminocarbonylamino-benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 46.1% of theory,
Melting point: sinters from 196 ° C
C₃₃H₃₈N₄O₄ × HCl (591.17)
Calc .: C 67.00 H 6.60 N 9.45
Found: C 67.22 H 6.74 N 9.49

Example 6 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6- (3,4,5,6-th trahydro-2 (1H) pyrimidinon-1-yl) benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -6- (3,4,5,6-tetrahydro-2 (1H) - pyrimidinone-1- yl) -benzimidazole and 1 N sodium hydroxide solution in ethanol
Yield: 8.8% of theory,
Melting point: 260-262 ° C
C₃₀H₃₂N₄O₄ (512.61)
Mass spectrum: (M + H) ⁺ = 513

Example 7 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6- (3-benzyl- 3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) - pyrimidinon-1-yl) benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 80.4% of theory,
Melting point: 124-126 ° C
C₃₇H₃₈N₄O₄ (602.74)
Calc .: C 73.73 H 6.35 N 9.30
Found: C 63.47 H 6.50 N 9.05

Example 8 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6- (N-cyclo hexylaminocarbonyl-methylamino) benzimidazole a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] - 6- (N-cyclohexylaminocarbonyl-methylamino) benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-6- (N-cyclohexylaminocarbonyl-methylamino) benzimidazole and 4 - [(α-ethoxycarbonyl) benzyloxy] benzyl bromide and subsequent chromatographic separation of the 2-n-butyl-1- [ 4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] -5- (N-cyclohexylaminocarbonylmethylamino) benzimidazole.
Yield: 50.0% of theory,
Oil, R _f value: 0.50 (silica gel; eluent: methyl ethyl ketone / xylene = 1: 1)

b) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6- (N-cyclo- hexylaminocarbonyl-methylamino) benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -6- (N-cyclohexylaminocarbonyl-methylamino) benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 93.0% of theory,
Melting point: 168-169 ° C
C₃₄H₄₀N₄O₄ (568.72)
Calc .: C 71.81 H 7.09 N 9.85
Found: C 71.78 H 7.02 N 9.71

Example 9 2-n-propyl-5- (2-methyl-propionylamino) -3- [4 - [(α-carboxy) - benzyloxy] benzyl] imidazo [4,5-b] pyridine a) 2-n-Propyl-5- (2-methyl-propionylamino) imidazo [4,5-b] pyridine

2.62 g (15 mmol) of 2-n-propyl-5-amino-imidazo [4,5-b] pyridine are suspended in 100 ml of absolute methylene chloride and, with stirring and ice-cooling, with 3.16 g (20 mmol) of isobutyric acid chloride transferred. A solution of 3.03 g (30 mmol) of triethylamine in 5 ml of methylene chloride is then added dropwise at -5 ° C. After one hour at room temperature, the reaction mixture is mixed with 100 ml of 2N hydrochloric acid and stirred for a further hour. The solution is then poured onto ice water and saturated sodium hydrogen carbonate solution is added. The aqueous phase is extracted 3 × with 100 ml of ethyl acetate, the combined organic phases are then washed with brine, dried over sodium sulfate and concentrated. The crude product is taken up in methylene chloride and purified on a silica gel column (particle size: 0.063-0.2 mm), initially using methylene chloride, later mixtures of methylene chloride and ethanol with increasing polarity (25: 1 and 19: 1) as the eluent. The uniform fractions are concentrated, the residue is triturated with petroleum ether / ether = 1: 1 and suction filtered.
Yield: 2.05 g (56% of theory),
Melting point: 206 ° C
C₁₃H₁₈N₄O (246.30)
Calc .: C 63.39 H 7.37 N 22.75
Found: C 63.64 H 7.57 N 22.98

(b) 2-n-Propyl-5- (2-methyl-propionylamino) -3- [4 - [(α-ethoxy carbonyl) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1a from 2-n-propyl-5- (2-methylpropionylamino) imidazo [4,5-b] pyridine and 4 - [(α-ethoxy carbonyl) benzyloxy] benzyl bromide.
Yield: 33.7% of theory,
Melting point: 100-101 ° C

c) 2-n-Propyl-5- (2-methyl-propionylamino) -3- [4 - [(α-carb oxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-5- (2-methylpropionylamino) -3- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] - imidazo [4,5-b] pyridine and 1 N sodium hydroxide solution in Ethanol.
Yield: 52.0% of theory,
Melting point: 134 ° C
C₂₈H₃₀N₄O₄ (486.58)
Calcd .: C 69.12 H 6.21 N 11.51
Found: C 69.03 H 6.11 N 11.36

Example 10 2-n-Butyl-5-valeroylamino-3- [4 - [(α-carboxy) benzyloxy] ben cyl] imidazo [4,5-b] pyridine semihydrate

Prepared analogously to Example 1b from 2-n-Buyl-5-valeroylamino-3- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] imidazo [4,5-b] pyridine and 1 N sodium hydroxide solution in ethanol.
Yield: 57.0% of theory,
Melting point: sinters from 96 ° C
C₃₀H₃₄N₄O₄ × 0.5 H₂O (532.65)
Calcd .: C 68.82 H 6.74 N 10.70
Found: C 68.99 H 6.67 N 10.58

Example 11 2-n-propyl-5- (1-methyl-benzimidazol-2-yl) -7-methyl-3- [4- [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-5- (1-methyl-benzimidazol-2-yl) -7-methyl-3- [4 - [(α-ethoxycarbonyl) benzyl] oxy] benzyl-imidazo [4, 5-b] pyridine and 1N sodium hydroxide solution in ethanol.
Yield: 41.4% of theory,
Melting point: 242-244 ° C
C₃₃H₃₁N₅O₃ (545.65)
Calcd .: C 72.64 H 5.73 N 12.83
Found: C 72.51 H 5.75 N 12.97

Example 12 2-n-propyl-6- (1-methyl-benzimidazol-2-yl) -4-methyl-1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-propyl-6- (1-methylbenzimidazol-2-yl) -4-methyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 41.0% of theory,
Melting point: amorphous
C₃₄H₃₂N₄O₃ (544.66)
Calc .: C 74.98 H 5.92 N 10.28
Found: C 74.55 H 6.06 N 10.08
Mass spectrum: (M + H) ⁺ = 545

Example 13 2-Methyl-4- [4 ′ - [(α-carboxy) benzyloxy] benzyloxy] quinoline a) 2-Methyl-4- [4 ′ - [(α-ethoxycarbonyl) benzyloxy] benzyloxy] - quinoline

Prepared analogously to Example 1a from 4-hydroxyquininaldine and 4 - [(α-ethoxycarbonyl) benzyloxy] benzyl bromide.
Yield: 19.8% of theory,
Oil, R _f value: 0.55 (silica gel; eluent: methylene chloride / ethanol = 19: 1)

b) 2-Methyl-4- [4 ′ - [(α-carboxy) benzyloxy] benzyloxy] quinoline

Prepared analogously to Example 1b from 2-methyl-4- [4 ′ - [(α-eth oxycarbonyl) benzyloxy] benzyloxy-quinoline and 1N sodium hydroxide solution in ethanol.
Yield: 66.6% of theory,
Melting point: 142-143 ° C
C₂₅H₂₁NO₄ (399.50)
Calc .: C 73.17 H 5.30 N 3.51
Found: C 73.56 H 5.25 N 3.34
Mass spectrum: (M + H) ⁺ = 400

Example 14 2-n-Propyl-5-n-butyrylamino-3- [4 - [(1-carboxy-3-methyl) butyl oxy] benzyl] imidazo [4,5-b] pyridine a) 2-n-Propyl-5-n-butyrylamino-3- [4 - [(1-methoxycarbonyl- 3-methyl) butyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1a from 2-n-propyl-5-n-butyrylamino-imidazo [4,5-b] pyridine and 4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl bromide, and subsequent chromatographic separation des 2-n-propyl-5-n-butyrylamino-1- [4- [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] imidazo [4,5-b] pyridine.
Yield: 47.0% of theory,
Oil, R _f value: 0.30 (silica gel; eluent: methylene chloride / ethanol = 19: 1)

b) 2-n-propyl-5-n-butyrylamino-3- [4- (1-carboxy-3-methyl) - butyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-5-n-butyrylamino-3- [4- (1-methoxycarbonyl-3-methyl) butyloxy] benzyl] - imidazo [4,5-b] pyridine and 1N sodium hydroxide solution in Ethanol.
Yield: 59.0% of theory,
Melting point: 147-148 ° C
C₂₆H₃₄N₄O₄ (466.59)
Calc .: C 66.93 H 7.35 N 12.01
Found: C 66.69 H 7.48 N 11.85

Example 15 2-n-butyl-1- [4 - [(α-carboxy) cyclohexylmethyloxy] benzyl] - benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-meth oxycarbonyl) cyclohexylmethyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 92.0% of theory,
Melting point: 208 ° C (dec.)
C₂₆H₃₂N₂O₃ (420.56)
Calc .: C 74.25 H 7.66 N 6.66
Found: C 73.98 H 7.52 N 6.41

Example 16 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) benzyl oxy] benzyl] imidazole a) 2-n-Butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-methoxycar bonyl) benzyloxy] benzyl] imidazole

Prepared analogously to Example 1a from 2-n-butyl-4-chloro-5-hydroxymethylimidazole and 4 - [(α-methoxycarbonyl) benzyloxy] - benzyl bromide, and subsequent chromatographic separation of the 2-n-butyl-5-chloro -4-hydroxymethyl-1- [4 - [(α-meth oxycarbonyl) benzyloxy] benzyl] imidazole.
Yield: 21.0% of theory,
Oil, R _f value: 0.70 (silica gel; eluent: methylene chloride / methanol = 6: 1)

b) 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) - benzyloxy] benzyl] imidazole hydrochloride

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] imide azole and 1N sodium hydroxide solution in ethanol.
Yield: 34.0% of theory,
Melting point: 176 ° C
C₂₃H₂₅ClN₂O₄ × HCl (465.38)
Calc .: C 59.36 H 5.63 N 6.02
Found: C 59.53 H 5.43 N 5.97

Example 17 2-n-butylchloro-4-hydroxymethyl-1- [4 - [(1-carboxy-3-methyl) - butyloxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-5-chloro-4-hydroxymethyl-1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benz yl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 66.0% of theory,
Melting point: 175-176 ° C
C₂₁H₂₉ClN₂O₄ (408.93)
Calculated: C 61.68 H 7.14 N 6.84
Found: C 61.34 H 7.11 N 6.58

Example 18 2-n-Butyl-5-chloro-4-hydroxymethyl-1- [4 - [(1-carboxy) -n-propyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-5-chloro-4-hydroxymethyl-1- [4 - [(1-methoxycarbonyl) -n-propoxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 70.0% of theory,
Melting point: 182-184 ° C
C₁₉H₂₅ClN₂O₄ (380.88)
Calc .: C 59.91 H 6.61 N 7.35
Found: C 59.67 H 6.53 N 7.22

Example 19 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-carboxy) -n-propyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-methoxycarbonyl) -n-propyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 66.0% of theory,
Melting point: 125-127 ° C
C₁₉H₂₅ClN₂O₄ (380.88)
Calc .: C 59.91 H 6.61 N 7.35
Found: C 59.74 H 6.60 N 6.90

Example 20 2-n-Butylchloro-5-methoxymethyl-1- [4 - [(α-carboxy) benzyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-meth oxymethyl-1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] imide azole and 1N sodium hydroxide solution in ethanol.
Yield: 45.0% of theory,
Melting point: 156-158 ° C
C₂₄H₂₇ClN₂O₄ (442.95)
Calc .: C 65.08 H 6.14 N 6.32
Found: C 64.70 H 6.38 N 6.03

Example 21 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-carboxy-3-methyl) butyloxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 57.0% of theory,
Melting point: 164-165 ° C
C₂₁H₂₉ClN₂O₄ (408.93)
Calculated: C 61.68 H 7.14 N 6.84
Found: C 61.63 H 7.09 N 6.71

Example 22 2-n-Butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-carboxy) benzyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-methoxycarbonyl) benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 18.0% of theory,
Melting point: 193 ° C
C₂₃H₂₅ClN₂O₄ (428.92)
R _f value: 0.10 (silica gel; eluent: methylene chloride / methanol = 9: 1)
Mass spectrum: (M + H) ⁺ = 394/396 (Cl)

Example 23 2-n-butyl-5-chloro-4-hydroxymethyl-1- [4 - [(1-carboxy) -n-butyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-5-chloro-4-hydroxymethyl-1- [4 - [(1-methoxycarbonyl) -n-butyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 27.0% of theory,
Melting point: 154 ° C
C₂₀H₂₇ClN₂O₄ (394.90)
R _f value: 0.20-0.30 (silica gel; mobile phase: methylene chloride / methanol = 9: 1)
Mass spectrum: (M + H) ⁺ = 394/396 (Cl)

Example 24 2-n-Butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-carboxy) -p-phe nyl-benzyloxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-methoxycarbonyl) -p-phenyl-benzyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 72.0% of theory,
Melting point: 182 ° C
C₂₉H₂₉ClN₂O₄ (505.02)
Calcd .: C 68.97 H 5.78 N 5.54
Found: C 68.50 H 5.83 N 5.46

Example 25 2-n-Butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) -p-phe nyl-benzyloxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-methoxycarbonyl) -p-phenyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 75.0% of theory,
Melting point: 185-186 ° C (dec.)
C₂₉H₂₉ClN₂O₄ (505.02)
Calcd .: C 68.97 H 5.78 N 5.54
Found: C 68.87 H 5.80 N 5.42

Example 26 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-carboxy) -2-naph thylmethyloxy] benzyl] imidazole semihydrate

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-methoxycarbonyl) -2-naphthylmethyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 69.0% of theory,
Melting point: from 188 ° C (decomp.)
C₂₇H₂₇ClN₂O₄ × 0.5 H₂O (487.99)
Calculated: C 66.45 H 5.78 N 5.74
Found: C 66.63 H 5.66 N 5.75

Example 27 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) -2-naph thylmethyloxy] benzyl] imidazole semihydrate

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxyoxymethyl-1- [4 - [(α-methoxycarbonyl) -2-naphthylmethyl oxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 82.0% of theory,
Melting point: 142 ° C (dec.)
C₂₇H₂₇ClN₂O₄ × 0.5 H₂O (487.99)
Calculated: C 66.45 H 5.78 N 5.74
Found: C 66.62 H 5.66 N 6.12

Example 28 2-n-Butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-carboxy) -1-naph thylmethyloxy] benzyl] imidazole hydrate

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-methoxycarbonyl) -1-naphthylmethyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 91.0% of theory,
Melting point: 110 ° C (decomp.)
C₂₇H₂₇ClN₂O₄ × H₂O (497.00)
Calc .: C 65.25 H 5.88 N 5.63
Found: C 65.58 H 5.89 N 5.83

Example 29 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) -1-naph thylmethyloxy] benzyl] imidazole hydrate

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-methoxycarbonyl) -1-naphthylmethyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 42.0% of theory,
Melting point: from 100 ° C (decomp.)
C₂₇H₂₇ClN₂O₄ × H₂O (497.00)
Calc .: C 65.25 H 5.88 N 5.63
Found: C 65.21 H 5.70 N 6.10

Example 30 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-carboxy) -p-meth oxy-benzyloxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(α-methoxycarbonyl) -p-methoxy-benzyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 58.0% of theory,
Melting point: 165 ° C
C₂₄H₂₇ClN₂O₅ (458.95)
Calculated: C 62.81 H 5.93 N 6.10
Found: C 62.69 H 6.02 N 5.93

Example 31 2-n-Butyl-4-chloro-5-methoxymethyl-1- [4 - [(1-carboxy) -p-pentyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-meth oxymethyl-1- [4 - [(1-methoxycarbonyl) -n-pentyloxy] benzyl] imide azole and 1N sodium hydroxide solution in ethanol.
Yield: 84.0% of theory,
Melting point: 168 ° C
C₂₂H₃₁ClN₂O₄ (422.96)
Calculated: C 62.45 H 7.38 N 6.62
Found: C 62.23 H 7.47 N 6.79

Example 32 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-carboxy) -n-butyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-methoxycarbonyl) butyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 50.0% of theory,
Melting point: 137-138 ° C
C₂₀H₂₇ClN₂O₄ (394.90)
Calculated: C 60.83 H 6.89 N 7.09
Found: C 60.67 H 6.94 N 6.67

Example 33 2-n-Butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-carboxy) -n-pentyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-methoxycarbonyl) -n-pentyloxy] benzyl] imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 61.0% of theory,
Melting point: 150 ° C
C₂₁H₂₉ClN₂O₄ (408.93)
Calculated: C 61.65 H 7.14 N 6.85
Found: C 62.31 H 6.85 N 7.21

Example 34 2-n-Butyl-4-hydroxymethyl-5-chloro-1- [4 - [(1-carboxy) -n-pentyl oxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(1-methoxycarbonyl) -n-pentyloxy] benzyl] imida zol and 1N sodium hydroxide solution in ethanol.
Yield: 57.0% of theory,
Melting point: 168 ° C
C₂₁H₂₉ClN₂O₄ (408.93)
Calculated: C 61.65 H 7.14 N 6.85
Found: C 61.59 H 7.11 N 6.91

Example 35 2-n-Butyl-8-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] china zolin-4-one semihydrate a) 2-n-Butyl-8-methyl-3- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] quinazolin-4-one

Prepared analogously to Example 1a from 2-n-butyl-8-methyl-china zolin-4 (1H) -one and 4- (α-ethoxycarbonyl-benzyloxy) benzylbro mid.
Yield: 37% of theory,
Oil, R _f value: 0.45 (silica gel; eluent: petroleum ether / ethyl acetate = 4: 1)

b) 2-n-butyl-8-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] quinazolin-4-one semihydrate

Prepared analogously to Example 1b from 2-n-butyl-8-methyl-3 - [(α-ethoxycarbonyl) benzyloxy] benzyl] quinazolin-4-one and 1N sodium hydroxide solution in ethanol.
Yield: 84% of theory,
Melting point: 201-204 ° C,
C₂₈H₂₈N₂O₄ × 0.5 H₂O (465.56)
Calc .: C 72.24 H 6.28 N 6.02
Found: C 72.41 H 6.33 N 5.75

Example 36 2-n-Butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-carboxy-2-cyclo hexyl) ethoxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-chloro-5-hydroxymethyl-1- [4 - [(1-methoxycarbonyl-2-cyclohexyl) ethoxy] benzylimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 67.1% of theory,
Melting point: 145-150 ° C
C₂₄H₃₃ClN₂O₄ (448.96)
Calc .: C 64.20 H 7.40 N 6.24
Found: C 63.97 H 7.38 N 6.01

Example 37 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(1-carboxy) -2-cyclo hexyl) ethoxy] benzyl] imidazole

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(1-methoxycarbonyl-2-cyclohexyl) ethoxy] benzyl imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 59.1% of theory,
Melting point: 180-183 ° C
C₂₄H₃₃ClN₂O₄ (448.96)
Calc .: C 64.20 H 7.40 N 6.24
Found: C 63.99 H 7.20 N 6.27
Mass spectrum: m / e = 448/450 (Cl)

Example 38 2-n-Butyl-1- [4 - [(1-carboxy-3-methyl) butyloxy] benzyl] benzimi dazol

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(1-meth oxycarbonyl-3-methyl) butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 82.3% of theory,
Melting point: 150-152 ° C
C₂₄H₃₀N₂O₃ (394.52)
Calc .: C 73.07 H 7.66 N 7.10
Found: C 72.83 H 7.37 N 7.14
Mass spectrum: m / e = 394

Example 39 2-n-Butyl-1- [4 - [(1-carboxy-2-cyclohexyl) ethoxy] benzyl] benzimi dazol

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(1-meth oxycarbonyl-2-cyclohexyl) ethoxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 82.0% of theory,
Melting point: 165-170 ° C
C₂₇H₃₄N₂O₃ (434.58)
Calculated: C 74.63 H 7.88 N 6.44
Found: C 74.46 H 7.77 N 6.30
Mass spectrum: m / e = 434

Example 40 2-n-Butyl-6-propionylamino-1- [4 - [(1-carboxy-3-methyl) butyl oxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6-propionylamino-1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 80.3% of theory,
Melting point: 120-130 ° C
C₂₇H₃₅N₂O₄ (465.59)
Calc .: C 69.65 H 7.58 N 9.02
Found: C 69.30 H 7.84 N 8.83
Mass spectrum: m / e = 465

Example 41 2-n-Butyl-5-propionylamino-1- [4 - [(1-carboxy-3-methyl) butyl oxy] benzyl] benzimidazole semihydrate

Prepared analogously to Example 1b from 2-n-butyl-5-propionylamino-1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] benz imidazole and 1N sodium hydroxide solution in ethanol.
Yield: 82.9% of theory,
Melting point: 165-170 ° C
C₂₇H₃₅N₃O₄ × 0.5 H₂O (474.60)
Calculated: C 68.32 H 7.64 N 8.85
Found: C 68.63 H 7.72 N 8.90

Example 42 2-n-butyl-6-cyclohexylaminocarbonylamino-1- [4 - [(1-carboxy-3- methyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6-cyclohexyl aminocarbonylamino-1- [4 - [(1-methoxycarbonyl-3-methyl) butyl oxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 90.8% of theory,
Melting point: 155-160 ° C
C₃₁H₄₂N₄O₄ (534.71)
Calcd .: C 69.64 H 7.92 N 10.48
Found: C 69.58 H 8.03 N 10.36
Mass spectrum: (M + H) ⁺ = 535

Example 43 2-n-butyl-5-cyclohexylaminocarbonylamino-1- [4 - [(1-carboxy-3- methyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-5-cyclohexyl aminocarbonylamino-1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 95.7% of theory,
Melting point: 220-225 ° C
C₃₁H₄₂N₄O₄ (534.71)
Calcd .: C 69.64 H 7.92 N 10.48
Found: C 69.49 H 7.99 N 10.52
Mass spectrum: (M + H) ⁺ = 535

Example 44 2-n-butyl-6- (N-propionyl-methylamino) -1- [4 - [(1-carboxy-3-me thyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (N-propionylmethylamino) -1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 66.8% of theory,
Melting point: 170-175 ° C
C₂₈H₃₇N₃O₄ (479.63)
Calc .: C 70.12 H 7.78 N 8.76
Found: C 70.35 H 7.85 N 8.91

Example 45 2-n-Butyl-5- (N-propionyl-methylamino) -1- [4 - [(1-carboxy-3-me thyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-5- (N-propionylmethylamino) -1- [4 - [(1-methoxycarbonyl-3-methyl) butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 62.0% of theory,
Melting point: 172-175 ° C
C₂₈H₃₇N₃O₄ (479.63)
Calc .: C 70.12 H 7.78 N 8.76
Found: C 70.11 H 7.80 N 8.63
Mass spectrum: m / e = 479

Example 46 2-n-butyl-6- (N-cyclohexylaminocarbonyl-methylamino) -1- [4 - [(1- carboxy-3-methyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (N-cyclohexylaminocarbonyl-methylamino) -1- [4 - [(1-methoxycarbonyl-3-methyl) - butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 76.1% of theory,
Melting point: 170-175 ° C
C₃₂H₄₄N₄O₄ (548.73)
Calc .: C 70.04 H 8.08 N 10.21
Found: C 69.95 H 8.10 N 10.22
Mass spectrum: m / e = 548

Example 47 2-n-butyl-5- (N-cyclohexylaminocarbonyl-methylamino) -1- [4 - [(1- carboxy-3-methyl) butyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-5- (N-cyclohexylaminocarbonyl-methylamino) -1- [4 - [(1-methoxycarbonyl-3-methyl) - butyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 72.9% of theory,
Melting point: 178-182 ° C
C₃₂H₄₄N₄O₄ (548.73)
Calc .: C 70.04 H 8.08 N 10.21
Found: C 69.77 H 7.97 N 10.04
Mass spectrum: m / e = 548

Example 48 2-n-butyl-3- [4 - [(α-carboxy) benzyloxy] -5-methyl-6- dimethylaminocarbonylamino-imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-butyl-3- [4 - [(α- (eth oxycarbonyl) benzyloxy] benzyl] -5-methyl-6-dimethylaminocarbonylamino-imidazo [4,5-b] pyridine and 2N sodium hydroxide solution in ethanol.
Yield: 80.0% of theory,
Melting point: 191-193 ° C
C₂₉H₃₃N₅O₄ (515.62)
Calc .: C 67.55 H 6.45 N 13.58
Found: C 67.49 H 6.62 N 13.57

Example 49 2-n-butyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] -5-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinon-1-yl) -imi dazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-butyl-3- [4 - [(α-eth oxycarbonyl) benzyloxy] benzyl] -5-methyl-6- (3-benzyl-3,4,5,6-th trahydro- 2 (1H) -pyrimidinon-1-yl) -imidazo [4,5-b] pyridine and 2N sodium hydroxide solution in ethanol.
Yield: 87.5% of theory,
Melting point: 157-160 ° C
C₃₇H₃₉N₅O₄ (617.75)
Calc .: C 71.94 H 6.36 N 11.34
Found: C 71.71 H 6.36 N 10.96

Example 50 2-n-butyl-6- (N-methylaminocarbonyl-n-pentylamino) -1- [4 - [(α- carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (N-methyl aminocarbonyl-n-pentylamino) -1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 76.0% of theory,
Melting point: 170-172 ° C
C₃₃H₄₀N₄O₄ (556.71)
Calc .: C 71.20 H 7.24 N 10.07
Found: C 70.80 H 7.34 N 9.96

Example 51 2-n-butyl-6- (N-cyclohexylaminocarbonyl-n-pentylamino) -1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (N-cyclohexylaminocarbonyl-n-pentylamino) -1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 65.0% of theory,
Melting point: 83 ° C
C₃₈H₄₈N₄O₄ (624.83)
Calc .: C 73.05 H 7.74 N 8.97
Found: C 72.80 H 7.51 N 8.59

Example 52 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-carboxy-α- phenyl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(α-methoxycarbonyl-α-phenyl) benzyloxy] benz yl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 50.0% of theory,
Melting point: 165 ° C (dec.)
C₂₉H₂₉ClN₂O₄ (505.02)
Calcd .: C 68.97 H 5.79 N 5.55
Found: C 68.50 H 5.72 N 5.51

Example 53 2-n-Butyl-6- (p-methylphenylsulfonylamino) -1- [4 - [(α-carb oxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (p-methylphenylsulfonylamino) -1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 81.0% of theory,
Melting point: 150 ° C
C₃₃H₃₃N₃O₅S (583.71)
Calc .: C 67.90 H 5.70 N 7.20
Found: C 67.18 H 5.70 N 6.96

Example 54 2-n-butyl-6- (N-methyl-p-methylphenylsulfonylamino) -1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (N-methyl-p-methylphenylsulfonylamino) -1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 96.0% of theory,
Melting point: 218 ° C
C₃₄H₃₅N₃O₅S (597.71)
Calc .: C 68.32 H 5.90 N 7.03
Found: C 67.82 H 5.84 N 6.85

Example 55 2-n-butyl-6- (N-n-pentyl-p-methylphenylsulfonylamino) -1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-6- (Nn-pentyl-p-methyl-phenylsulfonylamino) -1- [4 - [(α-methoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 94.0% of theory,
Melting point: 202 ° C
C₃₈H₄₃N₃O₅S (653.81)
Calc .: C 69.80 H 6.63 N 6.43
Found: C 69.47 H 6.57 N 6.64

Example 56 2-n-Butyl-1 - [(4 - [(α-carboxy) benzyloxy] - (α-methyl) benzyl] - benzimidazole a) 4 - [(α-ethoxycarbonyl) benzyloxy] acetophenone

Prepared analogously to Example 1a from ethyl 2-bromo-phenylacetate and 4-hydroxyacetophenone.
Yield: 78.0% of theory,
R _f value: 0.58 (silica gel; eluent: toluene / ethyl acetate = 85:15)

b) 1- [4 - [(α-ethoxycarbonyl) benzyloxy] phenyl] ethanol

2.3 g (7.7 mmol) of 4- (α-ethoxycarbonyl) benzyloxy] acetophenone are dissolved in 50 ml of ethanol, and 0.28 g (7.7 mmol) of sodium borohydride are added in portions at room temperature. The reaction mixture is stirred at 40 ° C for 2 hours. After cooling to room temperature, the mixture is concentrated and the residue is mixed with water and dilute hydrochloric acid. After extraction with ethyl acetate, the organic phase is dried with sodium sulfate. The solution is evaporated and the residue is chromatographed on a silica gel column (particle size: 0.063-0.02 mm) with toluene / ethyl acetate (7: 3). The uniform fractions are combined and evaporated.
Yield: 1.0 g (43% of theory),
Oil, R _f value: 0.50 (silica gel; eluent: toluene / vinegar ester = 7: 3)

c) 1- [4 - [(α-ethoxycarbonyl) benzyloxy] phenyl] -1-methanesul fonyloxy ethane

0.5 g (1.7 mmol) 1- [4 - [(α-ethoxycarbonyl) benzyloxy] phenyl] ethanol and 0.22 g (2.2 mmol) of triethylamine are dissolved in 10 ml Dissolved methylene chloride. At 5 ° C 0.23 g (2.0 mmol) of Me sylchloride added dropwise with stirring. After an hour at The reaction mixture is heated to ice water at room temperature pour, extracted with methylene chloride and over sodium sulfate dried. The crude product obtained is without further Rei directly implemented.

d) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] - (α-me thyl) benzyl] benzimidazole

A mixture of 0.26 g (1.5 mmol) of 2-n-butyl-benzimidazole, 3 ml (1.7 mmol) of triethylamine and 1- [4 - [(α-ethoxycarbonyl) benzyloxy] phenyl] -1-methanesulfonyloxy -ethane (raw) are heated to 80 ° C for 30 minutes. After cooling, water is added and extracted twice with ethyl acetate. The organic phases are combined, dried and evaporated. The crude product is chromatographed on a silica gel column (particle size: 0.063-0.02 mm) with toluene / ethyl acetate (8: 2). The uniform fractions are combined and evaporated.
Yield: 0.10 g (15% of theory),
R _f value: 0.35 (silica gel; eluent: toluene / ethyl acetate = 8: 2)

e) 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] - (α-methyl) ben cyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzyloxy] - (α-methyl) benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 82.0% of theory,
Melting point: 109 ° C
C₂₇H₂₈N₂O₃ (428.51)
Calc .: C 75.67 H 6.59 N 6.54
Found: C 75.93 H 6.76 N 6.32

Example 57 2-n-butyl-1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] -6- (3- benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) benzimidazole a) 5-Benzyl-1H-tetrazole

Made from benzyl cyanide and sodium azide / ammonium chloride in dimethylformamide.
Yield: 70% of theory,
Melting point: 130-132 ° C

b) N-triphenylmethyl-5-benzyl-tetrazole

Made from 5-benzyl-1H-tetrazole and triphenylmethyl chloride.
Yield: 84% of theory,
Melting point: 158-160 ° C

c) N-triphenylmethyl-5- (α-bromo) benzyl-tetrazole

2.0 g (5 mmol) of N-triphenylmethyl-5-benzyl-tetrazole, 0.89 g (5 mmol) of N-bromosuccinimide and 30 mg of azo-bisisobutyronitrile are dissolved in 25 ml of carbon tetrachloride and exposed to UV radiation for one hour Boiling heated. After cooling, the succinimide formed is filtered off and the filtrate is evaporated.
Yield: 74.6% of theory,
Melting point: 160-162 ° C

d) 2-n-Butyl-1 - [(4-benzyloxy) benzyl] -6- (3-benzyl-3,4,5,6-th trahydro-2 (1H) pyrimidinon-1-yl) benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) benzimidazole and 4-benzyloxybenzyl chloride.
Yield: 65.5% of theory,
R _f value: 0.45 (silica gel; eluent: methylene chloride / ethanol = 19: 1)

e) 2-n-Butyl-1 - [(4-hydroxy) benzyl] -6- (3-benzyl-3,4,5,6-tetra hydro-2 (1H) pyrimidinon-1-yl) benzimidazole

2.4 g of 2-n-butyl-1 - [(4-benzyloxy) benzyl] -6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) benzimidazole are dissolved in 100 ml of ethanol and 30 ml of dimethylformamide, mixed with 2.4 g of palladium on activated carbon (10%) and hydrogenated with 5 bar of hydrogen at room temperature. The catalyst is filtered off, the filtrate is evaporated and the residue is chromatographed on a silica gel column (particle size: 0.063-0.02 mm) with methylene chloride / ethanol. The uniform fractions are combined and evaporated, the residue is triturated with ether and suction filtered.
Yield: 1.1 g (55% of theory),
Melting point: 190-191 ° C

f) 2-n-Butyl-1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) ben zyloxy] benzyl] -6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimi dinon-1-yl) benzimidazole

0.5 g (1.1 mmol) of 2-n-butyl-1 - [(4-hydroxy) benzyl] -6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone- 1-yl) -benzimidazole, 0.74 g (5.4 mmol) of potassium carbonate and 0.93 g (1.1 mmol) of N-tri phenylmethyl-5 - [(α-bromo) benzyl] tetrazole are dissolved in 10 ml of dimethyl sulfoxide dissolved and stirred for 2 hours at room temperature. The product is precipitated by adding saline, suction filtered, washed with water and dried.
Yield: 0.9 g (97% of theory),
Melting point: from 150 ° C (decomp.)

g) 2-n-butyl-1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] - 6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) - benzimidazole

0.9 g (1.0 mmol) of 2-n-butyl-1- [4 - [(α-N-triphenylmethyl) te trazol-5-yl) benzyloxy] benzyl] -6- (3-benzyl-3, 4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) benzimidazole are dissolved in 40 ml of ethanol, 10 ml of methylene chloride and 12 ml of 4N hydrochloric acid and stirred for 2 hours at room temperature. After adding 30 ml of water, the mixture is extracted with methylene chloride. The organic phase is washed with 1N sodium hydroxide solution, acidified with dilute acetic acid and dried over sodium sulfate. The crude product is chromatographed on a silica gel column (particle size: 0.063-0.02 mm) with methylene chloride / ethanol (50: 1 and 19: 1). The uniform fractions are combined and evaporated.
Yield: 0.22 g (34% of theory),
Melting point: from 134 ° C (decomp.)
C₃₇H₃₈N₈O₂ (626.76)
Calc .: C 70.90 H 6.11 N 17.88
Found: C 70.72 H 6.00 N 17.68

Example 58 2-n-propyl-4-methyl-1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole a) 2-n-Propyl-4-methyl-1- [4 - [(α- (N-triphenylmethyl) tetra zol-5-yl) benzyloxy] benzyl benzimidazole

Prepared analogously to Example 57f from 2-n-propyl-4-methyl-1 - [(4-hydroxy) benzyl] benzimidazole and N-triphenylmethyl-5- [(α-bromo) benzyl] tetrazole.
Yield: 99% of theory,
R _f value: 0.68 (silica gel; eluent: methylene chloride / methanol = 19: 1)

b) 2-n-Propyl-4-methyl-1- [4- [α- (1H-tetrazol-5-yl) benzyl oxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-propyl-4-methyl-1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] benzimidazole and methanolic hydrochloric acid.
Yield: 63% of theory,
Melting point: amorphous
C₂₆H₂₆N₆O (438.54)
Calc .: C 71.21 H 5.98 N 19.17
Found: C 70.99 H 5.98 N 18.96

Example 59 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole a) 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] ben cyl] benzimidazole

Prepared analogously to Example 57f from 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1 - [(4-hydroxy) benzyl] benzimidazole (synthesis analogously to Examples 58d and 58e) and N. -Triphenylmethyl- 5- (α-bromo) benzyl-tetrazole.
Yield: 94% of theory,
R _f value: 0.70 (silica gel; eluent: methylene chloride / methanol = 9: 1)

b) 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] benzimidazole and methanolic hydrochloric acid.
Yield: 62% of theory,
Melting point: 165-166 ° C
C₃₄H₃₂N₈O (568.69)
Calc .: C 71.81 H 5.67 N 19.71
Found: C 71.68 H 5.60 N 19.55

Example 60 2-n-Propyl-5-n-butyrylamino-3- [4 - [(1- (1H-tetrazol-5-yl) -3-me thyl) butyloxy] benzyl] imidazo [4,5-b] pyridine a) 2-n-Propyl-5-n-butyrylamino-3- [4 - [(1-cyano-3-methyl) butyl oxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 57f from 2-n-propyl-5-n-butyrylamino-3 - [(4-hydroxy) benzyl] imidazo [4,5-b] pyridine and 2-bromo-4-methylvaleronitrile.
Yield: 85% of theory
R _f value: 0.40 (silica gel, mobile phase: ethyl acetate / petroleum ether = 1: 1)

b) 2-n-propyl-5-n-butyrylamino-3- [4 - [(1- (1H-tetrazol-5-yl) - 3-methyl) butyloxy] benzyl] imidazo [4,5-b] pyridine

A mixture of 800 mg (1.78 mmol) of 2-n-propyl-5-n-butyrylamino-3- [4 - [(1-cyano-3-methyl) butyloxy) benzyl] imidazo [4,5-b ] pyridine, - 2.2 g (3.3 mmol) of sodium azide and 1.8 g (3.3 mmol) of ammonium chloride in 8 ml of dimethylformamide is stirred for 5 hours at 130 ° C. The mixture is then stirred in ice water, the precipitated product is filtered off with suction, washed with water, dried and purified on a silica gel column (methylene chloride / ethanol = 19: 1). The fractions containing the desired substance are concentrated, the residue obtained is triturated with ether, suction filtered and dried. Repeating the cleaning step described above gives 370 mg (42% of theory) of melting point 175-177 ° C.
C₂₆H₃₄N₈O₂ (490.61)
Calc .: C 63.65 H 6.99 N 22.84
Found: C 63.61 H 7.03 N 22.83

Example 61 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4 - [(1H-tetrazole- 5-yl) propyloxy] benzyl] benzimidazole sesquihydrochloride

Prepared analogously to Example 60b from 2-n-butyl-4-hydroxymethyl-5-chloro-1- [4- (1-cyano-propyloxy) benzyl] imidazole and sodium azide / ammonium chloride in dimethylformamide.
Yield: 78% of theory,
Oil, C₁₉H₂₅ClN₆O₂ × 1.5 HCl (459.59)
Calcd .: C 49.65 H 5.81 N 18.28
Found: C 49.41 H 6.03 N 18.52

Example 62 2-n-butyl-5-hydroxymethyl-4-chloro-1- [4 - [(1- (1H-tetrazole- 5-yl) propyloxy] benzyl] benzimidazole sesquihydrochloride

Prepared analogously to Example 60b from 2-n-butyl-5-hydroxymethyl-4-chloro-1- [4- (1-cyano-propyloxy) benzyl] imidazole and sodium azide / ammonium chloride in dimethylformamide.
Yield: 70% of theory,
Oil, C₁₉H₂₅ClN₆O₂ × 1.5 HCl (459.59)
Calcd .: C 49.65 H 5.81 N 18.28
Found: C 49.86 H 5.76 N 18.26

Example 63 2-n-butyl-1- [4 - [(α-carboxy) benzylamino] benzyl] benzimidazole- semihydrate a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzylamino] benzyl] benzimidazole

1.0 g (3.6 mmol) of 2-n-butyl-1 - [(4-amino) benzyl] benzimidazole, 0.87 g (3.6 mmol) of ethyl 2-bromo-phenylacetate and 0.5 g of sodium acetate. trihydrate are dissolved in 20 ml of ethanol and stirred for 18 hours at room temperature. The reaction mixture is then heated under reflux for a further 4 hours. The solvent is evaporated, the residue is mixed with water, made alkaline with dilute ammonia solution and extracted with ethyl acetate. The combined organic phases are washed with water, dried over magnesium sulfate and evaporated. The residue is purified on a silica gel column (particle size: 0.063-0.02 mm), petroleum ether with 10-15% ethyl acetate being used as the eluent. The uniform fractions are combined and evaporated.
Yield: 1.0 g (63% of theory),
R _f value: 0.53 (silica gel; mobile phase: petroleum ether / vinegar ester = 3: 1)

b) 2-n-Butyl-1- [4 - [(α-carboxy) benzylamino] benzyl] benzimida zol semihydrate

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) benzylamino] benzyl] benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 99% of theory,
C₂₆H₂₇N₃O₂ × 0.5 H₂O (422.54)
Calc .: C 73.91 H 6.68 N 9.95
Found: C 74.05 H 6.55 N 9.91

Example 64 2-n-butyl-1- [4 - [(α-carboxy) -N-acetyl-benzylamino] benzyl] benzimidazole a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) -N-acetyl-benzyl amino] benzyl] benzimidazole

0.5 g (1.1 mmol) of 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzylamino] benzyl] benzimidazole are dissolved in 5 ml of acetic anhydride and stirred at 120 ° C. for 3 hours. The solvent is drawn off, the residue is purified on a silica gel column (particle size: 0.063-0.02 mm), ethyl acetate being used as the eluent. The uniform fractions are combined and evaporated.
Yield: 0.35 g (64% of theory),
R _f value: 0.50 (silica gel; eluent: methylene chloride / ethanol = 95: 5)

b) 2-n-Butyl-1- [4 - [(α-carboxy) -N-acetyl-benzylamino] ben cyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-eth oxycarbonyl) -N-acetyl-benzylamino] benzyl] benzimidazole and 1 N sodium hydroxide solution in ethanol.
Yield: 74% of theory,
Melting point: 212-214 ° C
C₂₈H₂₉N₃O₃ (455.56)
Calc .: C 73.82 H 6.42 N 9.12
Found: C 73.50 H 6.58 N 9.28

Example 65 2-n-Butyl-1- [4 - [(2-carboxy-3-phenyl) propyl] benzyl] benzimidazole a) 2-n-Butyl-1 - [(4-hydroxymethyl) benzyl] benzimidazole

1.2 g (30 mmol) of lithium aluminum hydride are suspended in 200 ml of absolute tetrahydrofuran. A solution of 10.6 g (30 mmol) of 2-n-butyl-1 - [(4-ethoxycarbonyl) benzyl] benzimidazole in 100 ml of absolute tetrahydrofuran is added dropwise at room temperature. The mixture is stirred for 2 hours at room temperature and then slowly hydrolyzed with cooling with aqueous sodium hydroxide solution. The crystallized salts are suctioned off and the filtrate is concentrated. The residue is mixed with water and extracted with ethyl acetate. The combined organic phases are washed with water, dried and evaporated. The residue is purified on a silica gel column (particle size: 0.063-0.02 mm), methylene chloride / methanol (30: 1) being used as the eluent. The uniform fractions are combined and evaporated.
Yield: 6.5 g (74% of theory),
R _f value: 0.60 (silica gel; eluent: methylene chloride / methanol = 19: 1)

b) 2-n-Butyl-1 - [(4-chloromethyl) benzyl] benzimidazole

6.2 g (21 mmol) of 2-n-butyl-1 - [(4-hydroxymethyl) benzyl] benzimidazole are dissolved in 10 ml of thionyl chloride and boiled under reflux for 10 minutes. Excess thionyl chloride is then distilled off and ice water is added to the residue. After neutralization with saturated sodium bicarbonate solution, the mixture is extracted with ethyl acetate. The combined organic phases are washed with water, dried and concentrated.
Yield: 6.0 g (91% of theory),
R _f value: 0.65 (silica gel; eluent: methylene chloride / methanol = 19: 1)

c) 2-n-butyl-1- [4 - [(2,2-bis-ethoxycarbonyl-3-phenyl) propyl] benzyl] benzimidazole

2.4 g (9.6 mmol) of diethyl benzylmalonate are dissolved in 25 ml of dimethyl sulfoxide, 1.1 g (9.6 mmol) of potassium tert-butoxide are added and the mixture is stirred at room temperature for 30 minutes. A solution of 3.0 g (9.6 mmol) of 2-n-butyl-1 - [(4-chloromethyl) benzyl] benzimidazole in 25 ml of dimethyl sulfoxide is then added dropwise. After one hour at room temperature, the mixture is heated to 100 ° C. for a further 15 minutes. Ice water is added to the reaction mixture. The crystallized product is filtered off and extracted with ethyl acetate. The combined organic phases are washed with water, dried and concentrated.
Yield: 4.2 g (83% of theory),
R _f value: 0.15 (silica gel; eluent: methylene chloride / methanol = 30: 1)

d) 2-n-Butyl-1- [4 - [(2-carboxy-3-phenyl) propyl] benzyl] benzimidazole

0.44 g (0.8 mmol) of 2-n-butyl-1- [4 - [(2,2-bis-ethoxycarbonyl-3-phenyl) propyl] benzyl] benzimidazole and 0.12 g of sodium hydroxide are dissolved in 30 ml Water was taken up and boiled under reflux for 8 hours. Then it is acidified with glacial acetic acid. The product which has crystallized out is filtered off with suction and purified over a silica gel acid (particle size: 0.063-0.02 mm), methylene chloride / methanol (19: 1) being used as the eluent. The uniform fractions are combined, evaporated, triturated with ether, suction filtered and dried.
Yield: 0.1 g (39% of theory),
Melting point: 139-140 ° C
C₂₈H₃₀N₂O₂ (426.56)
Calc .: C 78.84 H 7.09 N 6.57
Found: C 78.72 H 6.96 N 6.56

Example 66 2-n-Butyl-1- [4 - [(2-carboxy-2-phenyl) ethyl] benzyl] benzimidazole a) 2-n-Butyl-1- [4- (2,2-bis-ethoxycarbonyl-2-phenyl) ethyl) benzyl] benzimi-dazole

Prepared analogously to Example 65c from 2-n-butyl-1 - [(4-chloromethyl) benzyl] benzimidazole and diethyl phenylmalonate / potassium tert-butoxide.
Yield: 82% of theory,
R _f value: 0.20 (silica gel; eluent: methylene chloride / methanol = 40: 1)

b) 2-n-Butyl-1- [4 - [(2-carboxy-2-phenyl) ethyl] benzyl] benzimidazole

Prepared analogously to Example 65d from 2-n-butyl-1- [4- [2,2-bis-ethoxycarbonyl-2-phenyl) ethyl] benzyl] benzimidazole and aqueous sodium hydroxide solution in ethanol.
Yield: 37% of theory,
Melting point: 171-172 ° C
C₂₇H₂₈N₂O₂ (412.54)
Calculated: C 78.44 H 6.66 N 6.88
Found: C 78.61 H 6.84 N 6.79

Example 67 2-n-propyl-5- (N-ethyl-cyclohexylcarbonylamino) -3- [4 - [(α- carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-5- (N-ethylcyclohexylcarbonylamino) -3- [4- (α-ethoxycarbonyl) benzyloxy] benzyl] imidazo [4,5-b] pyridine and 1N sodium hydroxide solution in ethanol.
Yield: 87% of theory,
Melting point: 113-115 ° C
C₃₃H₃₈N₄O₄ (554.70)
Calc .: C 71.46 H 6.91 N 10.10
Found: C 71.60 H 6.99 N 10.00

Example 68 2-n-propyl-5- (N-cyclohexylaminocarbonyl-ethylamino) -3- [4- [(α-carboxy) benzyloxy] benzyl imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-5- (N-cyclohexylaminocarbonylethylamino) -3- [4- (α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 20% of theory,
Melting point: 183 ° C
C₃₃H₃₉N₅O₄ (569.72)
Calc .: C 69.57 H 6.90 N 12.29
Found: C 69.80 H 6.69 N 11.97

Example 69 2-n-butyl-4-methyl-7- [α- (1H-tetrazol-5-yl) benzyloxy-1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-4-methyl-7- [α- (1-triphenylmethyl-tetrazol-5-yl) benzyloxy] -1- [4- [α- (1-triphenylmethyl) tetrazole-5 -yl) benzyloxy] benzyl] benzimidazole and 4N hydrochloric acid.
Yield: 52% of theory,
Melting point: from 166 ° C (decomp.)
C₃₅H₃₄N₁₀O₂ (626.72)
Calculated: C 67.68 H 5.46 N 22.35
Found: C 67.70 H 5.52 N 22.66

Example 70 2-n-butyl-5-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone- 1-yl) -3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 57 from 2-n-butyl-5-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinon-1-yl) -3- [4- [α - (1-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] imidazo- [4,5-b] pyridine and 4N hydrochloric acid.
Yield: 75% of theory,
Melting point: 185-187 ° C
C₃₇H₃₉N₉O₂ (661.79)
Calculated: C 69.24 H 6.12 N 19.64
Found: C 68.97 H 6.17 N 19.91

Example 71 2-n-butyl-5-dimethylaminocarbonylamino-1- [4- [α- (1H-tetrazole- 5-yl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-5-dimethylaminocarbonylamino-1- [4- [α- (1-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] benzimidazole and 4N hydrochloric acid.
Yield: 66% of theory,
Melting point: 207-209 ° C
C₂₉H₃₂N₈O₂ (524.68)
Calc .: C 64.19 H 6.31 N 20.65
Found: C 63.95 H 6.33 N 20.44

Example 72 2-ethyl-5,7-dimethyl-3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] - benzyl] imidazo [4,5-b] pyridine semihydrate

Prepared analogously to Example 57g from 2-ethyl-5,7-dimethyl-3- [4- [α- (1-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] imidazo [4,5-b] pyridine semihydrate and 4N hydrochloric acid.
Yield: 83% of theory,
Melting point: 104-105 ° C
C₂₅H₂₅N₇O × 0.5 H₂O (448.53)
Calc .: C 66.95 H 5.89 N 21.83
Found: C 67.05 H 5.94 N 22.36

Example 73 2-n-propyl-4-methyl-1- [4- [α- (O-ethylphosphono) benzylamino] - benzyl] benzimidazole hydrate a) 2-n-Propyl-4-methyl-1- [4- [α- (O, O-diethyl-phosphono) - benzylamino] benzyl] benzimidazole

6.5 g (23.3 mmol) of 2-n-propyl-4-methyl-1 - [(4-amino) benzyl] benzimidazole are stirred into 4.2 g (40 mmol) of benzaldehyde. The mixture is stirred for 2 hours at room temperature. Then 10.72 g (77.6 mmol) of diethyl phosphite are added and the mixture is heated to 100 ° C. for 45 minutes. The precipitate formed after cooling to room temperature is triturated with 250 ml of ether, suction filtered and air-dried. It is then recrystallized from 150 ml of petroleum ether / isopropanol (2: 1).
Yield: 8.7 g (74% of theory),
Melting point: 110-115 ° C

b) 2-n-propyl-4-methyl-1- [4- [α- (O-ethylphosphono) benzyl- aminobenzyl] benzimidazole hydrate

0.5 g (1 mmol) of 2-n-propyl-4-methyl-1- [4- [α- (O, O-diethylphosphono) benzylamino] benzyl] benzimidazole and 1.0 g of powdered potassium hydroxide are dissolved in 20 ml of methanol dissolved and heated under reflux for 9 hours. After cooling to room temperature, 25 ml of ice water are added. The pH is adjusted by adding glacial acetic acid and conc. Ammonia solution set to 6.5. After adding solid sodium chloride, the mixture is extracted 6 times with 100 ml of ethyl acetate each time. The combined organic phases are washed with saturated sodium chloride solution and dried over magnesium sulfate. After evaporation of the solvent in vacuo, the residue is triturated with ether and dried over potassium hydroxide.
Yield: 0.35 g (73% of theory),
Melting point: from 158 ° C (decomp.)
C₂₇H₃₂N₃O₃P × H₂O (495.57)
Calc .: C 65.44 H 6.92 N 8.48
Found: C 65.66 H 6.52 N 8.49

Example 74 2-n-butyl-1- [4- [α- (O-ethylphosphono) benzylamino] benzyl] - benzimidazole a) 2-n-Butyl-1- [4- [α- (O, O-diethyl-phosphono) benzylamino] - benzyl] benzimidazole

Prepared analogously to Example 73a from 2-n-butyl-1 - [(4-amino) benzyl] benzimidazole, benzaldehyde and diethyl phosphite.
Yield: 51% of theory,
Melting point: 149-153 ° C

b) 2-n-Butyl-1- [4- [α- (O-ethylphosphono) benzylamino] benzyl] benzimidazole

Prepared analogously to Example 73b from 2-n-butyl-1- [4-α- (O, O-diethyl-phosphono) benzylamino] benzyl] benzimidazole and methanolic potassium hydroxide solution.
Yield: 67% of theory,
Melting point: 118-123 ° C (decomp.)
C₂₇H₃₂N₃O₃P (477.55)
Calc .: C 67.91 H 6.76 N 8.80
Found: C 67.74 H 7.02 N 8.64

Example 75 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole a) 2-n-Butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1a from 2-n-butylbenzimidazole and 4 - [(α-ethoxycarbonylbenzyloxy) benzyl] bromide.
Yield: 22.0% of theory,
Oil, R _f value: 0.65 (silica gel; eluent: ethyl acetate / ethanol = 9: 1)
C₂₈H₃₀N₂O₃ (442.60)
Calc .: C 75.99 H 6.83 N 6.33
Found: C 75.97 H 6.79 N 5.99

b) 2-n-Butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 38.0% of theory,
Melting point: 223-225 ° C
C₂₆H₂₆N₂O₃ (414.51)
Calc .: C 75.34 H 6.32 N 6.76
Found: C 75.03 H 6.34 N 6.73

Example 76 2-n-Propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine a) 2-n-Propyl-7-methyl-3- [4- [α-ethoxycarbonyl) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1a from 2-n-propyl-7-methyl-imidazo [4,5-b] pyridine and 4 - [(α-ethoxycarbonyl) benzyloxy] benzyl bromide.
Yield: 34.0% of theory,
Oil, R _f value: 0.40 (silica gel; eluent: methylene chloride / ethanol = 25: 1)

b) 2-n-Propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-propyl-7-methyl-3- [4- [(α-ethoxycarbonyl) benzyloxy] benzyl] imidazo [4,5-b] pyridine and 1N sodium hydroxide solution in ethanol.
Yield: 66.4% of theory,
Melting point: 108 ° C
C₂₅H₂₅N₃O₃ (415.50)
Calc .: C 72.27 H 6.06 N 10.11
Found: C 72.25 H 6.03 N 9.87

Example 77 5,7-dimethyl-2-ethyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine semihydrate

Prepared analogously to Example 1b from 5,7-dimethyl-2-ethyl-3- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] imidazole [4,5-b] pyridine and 1N sodium hydroxide solution in ethanol.
Yield: 89.3% of theory.,
Melting point: 251-253 ° C,
C₂₅H₂₅N₃O₃ × 0.5 H₂O (424.50)
Calc .: C 70.73 H 6.17 N 9.89
Found: C 71.00 H 5.97 N 9.79

Example 78 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] -3,5-dichlorobenzyl] - 6-cyclohexylaminocarbonylamino-benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] -3,5-dichlorobenzyl] -6-cyclohexylamino-carbonylamino-benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 95.6% of theory,
Melting point: 251-253 ° C
C₃₃H₃₆Cl₂N₄O₄ (623.58)
Calc .: C 63.56 H 5.82 N 8.98 Cl 11.37
Found: C 63.39 H 5.88 N 8.87 Cl 11.85

Example 79 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] -3-methoxybenzyl] - 6-dimethylaminocarbonylamino-benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] -3-methoxybenzyl] -6-dimethylaminocarbonylamino-benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 87.5% of theory,
Melting point: 170-172 ° C
C₃₀H₃₄N₄O₅ (530.62)
Calc .: C 67.90 H 6.46 N 10.56
Found: C 67.64 H 6.25 N 10.33

Example 80 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] -3-methoxybenzyl] - 5-dimethylaminocarbonylamino-benzimidazole

Prepared analogously to Example 1b from 2-n-butyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] -3-methoxybenzyl] -5-dimethylaminocarbonylamino-benzimidazo-1 and 2N sodium hydroxide solution in ethanol.
Yield: 78.6% of theory,
Melting point: 154-156 ° C
C₃₀H₃₄N₄O₅ (530.62)
Calc .: C 67.90 H 6.46 N 10.56
Found: C 67.74 H 6.37 N 10.24

Example 81 2-n-propyl-1- [4 - [(α-carboxy) benzyloxy] -3,5-dimethoxybenzyl] - 6- (1-methyl-benzimidazol-2-yl) -4-methyl-benzimidazole hydrate

Prepared analogously to Example 1b from 2-n-propyl-1 - [4 - [(α-ethoxycarbonyl) benzyloxy] -3,5-dimethoxybenzyl] -6- (1-methyl-benzimidazol-2-yl) -4-methyl- benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 91.4% of theory,
Melting point: 148-150 ° C
C₃₆H 20602 00070 552 001000280000000200012000285912049100040 0002004142366 00004 20483 ¶N₄O₅ × H₂O (622.72)
Calc .: C 69.44 H 6.25 N 9.00
Found: C 69.77 H 6.09 N 8.92

Example 82 2-n-propyl-1- [4 - [(α-carboxy) benzyloxy] -3,5-dibromobenzyl] - 6- (1-methyl-benzimidazol-2-yl) -4-methyl-benzimidazole hydrate

Prepared analogously to Example 1b from 2-n-propyl-1- [4 - [(α-ethoxycarbonyl) benzyloxy] -3,5-dibromobenzyl] -6- (1-methyl-benzimidazol-2-yl) -4-methyl- benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 58.4% of theory,
Melting point: 229-230 ° C
C₃₄H₃₀Br₂N₄O₃ × H₂O (720.46)
Calc .: C 56.68 H 4.47 N 7.77
Found: C 56.78 H 4.64 N 7.75

Example 83 2-n-propyl-6- (2,3-dimethylsuccinimino) -1- [4 - [(α-carboxy) benzyloxy] -3,5-dimethoxybenzyl] benzimidazole semihydrate

Prepared analogously to Example 1b from 2-n-propyl-6- (2,3-dimethylsuccinimino) - 1- [4 - [(α-ethoxycarbonyl) benzyloxy] -3,5-dimethoxybenzyl] benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 13.8% of theory,
Melting point: 120-131 ° C
C₃₄H₃₇N₃O₇ × 0.5 H₂O (608.69)
Calc .: C 67.09 H 6.29 H 6.90
Found: C 67.29 H 6.37 H 6.86

Example 84 2-n-butyl-6- (1-cyclohexene-1,2-dicarbonylimino) -1- [4 - [(α- carboxy) benzyloxy] benzyl] benzimidazole semihydrate

Prepared analogously to Example 1b from 2-n-butyl-6- (1-cyclohexene-1,2-dicarbonylimino) -1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and 1N sodium hydroxide solution in ethanol.
Yield: 23.3% of theory,
Melting point: 247-249 ° C
C₃₄H₃₃N₃O₅ × 0.5 H₂O (572.66)
Calc .: C 71.30 H 5.98 N 7.33
Found: C 71.47 H 6.05 N 7.15

Example 85 2-n-Propyl-4-methyl-1- [4 - [(α-carboxy) -2-chlorobenzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-propyl-4-methyl-1- [4- [(α-ethoxycarbonyl) -2-chlorobenzyloxy] benzyl] benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 40.7% of theory,
Melting point: sinter from 105 ° C
C₂₆H₂₅ClN₂O₃ (448.97)
Calc .: C 70.00 H 5.62 N 6.28 Cl 7.91
Found: C 69.94 H 5.72 N 6.29 Cl 7.92

Example 86 2-n-propyl-4-chloro-6- (1-oxo-2-isoindolin-2-yl) -1- [4 - [(α- carboxy) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 1b from 2-n-propyl-4-chloro-6- (1-oxo-2-isoindolin-2-yl) -1- [4 - [(α-ethoxycarbonyl) benzyloxy] benzyl] benzimidazole and 2N sodium hydroxide solution in ethanol.
Yield: 61.0% of theory,
Melting point: 252-254 ° C
C₃₃H₂₈ClN₃O₄ (566.06)
Calc .: C 70.00 H 5.02 N 7.42 Cl 6.25
Found: C 69.81 H 5.22 N 7.87 Cl 6.54

Example 87 2-n-butyl-6- (1-cyclohexene-1,2-dicarbonylimino) -1- [4 - [(α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-6- (1-cyclohexene-1,2-dicarbonylimino) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] benzimidazolimidazole and 85% formic acid in methylene chloride.
Yield: 43.7% of theory,
Melting point: 149-151 ° C
C₃₄H₃₃N₇O₃ (587.68)
Calculated: C 69.49 H 5.66 N 16.68
Found: C 69.40 H 5.83 N 16.31

Example 88 2-n-butyl-5-methyl-6-dimethylaminocarbonylamino-3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] imidazole [4,5-b] pyridine

Prepared analogously to Example 57g from 2-n-butyl-5-methyl-6-dimethylaminocarbonylamino-3- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] imidazole [4,5-b ] pyridine and 4N hydrochloric acid in ethanol.
Yield: 75% of theory,
Melting point: 198-200 ° C
C₂₉H₃₃N₉O₂ (539.64)
Calc .: C 64.54 H 6.16 N 23.36
Found: C 64.37 H 6.24 N 23.57

Example 89 2-n-butyl-6- (cyclohexylaminocarbonyl-N-methylamino) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-6- (cyclohexylaminocarbonyl-N-methylamino) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] benzimidazole and 4N hydrochloric acid in Ethanol.
Yield: 85.7% of theory,
Melting point: 195-197 ° C
C₃₄H₄₀N₈O₂ (592.74)
Calc .: C 68.89 H 6.80 N 18.90
Found: C 68.82 H 6.91 N 18.77

Example 90 5,7-dimethyl-2-ethyl-3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] - 3,5-dichlorobenzyl] imidazo [4,5-b] pyridine hydrate

Prepared analogously to Example 57g from 5,7-dimethyl-2-ethyl-3- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3,5-dichlorobenzyl] imida-zo [4, 5-b] pyridine and 85% formic acid in methylene chloride.
Yield: 77.2% of theory,
Melting point: 143-145 ° C
C₂₅H₂₃Cl₂N₇O × H₂O (526.42)
Calc .: C 57.04 H 4.78 N 18.62 Cl 13.47
Found: C 57.51 H 4.82 N 19.03 Cl 13.38

Example 91 2-n-butyl-6-cyclohexylaminocarbonylamino-1- [4- [α- (1H-tetrazole- 5-yl) benzyloxy] -3,5-dichlorobenzyl] benzimidazole semihydrate

Prepared analogously to Example 57g from 2-n-butyl-6-cyclohexylaminocarbonylamino- 1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3,5-dichlorobenzyl] -benzimidazole and 85% strength Formic acid in methylene chloride.
Yield: 83% of theory,
Melting point: 129-131 ° C
C₃₃H₃₆Cl₂N₈O₂ × 0.5 H₂O (655.62)
Calc .: C 60.36 H 5.68 N 17.07
Found: C 60.40 H 5.78 N 17.19

Example 92 2-n-butyl-6-dimethylaminocarbonylamino-1- [4- [α- (1H-tetrazole- 5-yl) benzyloxy] -3-methoxybenzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-6-dimethylaminocarbonylamino- 1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3-methoxybenzyl] benzimidazole and 4N hydrochloric acid in ethanol.
Yield: 75% of theory,
Melting point: 158-162 ° C
C₃₀H₃₄N₈O₃ (554.65)
Calc .: C 64.97 H 6.18 N 20.20
Found: C 64.71 H 6.20 N 19.91

Example 93 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] -3,5-dimethoxybenzyl] benzimidazole hydra-t

Prepared analogously to Example 57g from 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3,5-dimethoxybenzyl] benzimidazole and 85% formic acid in methylene chloride.
Yield: 83% of theory,
Melting point: 152-154 ° C
C₃₆H₃₆N₈O₃ × H₂O (646.75)
Calc .: C 66.86 H 5.97 N 17.33
Found: C 67.08 H 5.99 N 16.97

Example 94 2-n-propyl-4-methyl-6- (2,3-dimethylsuccinimino) -1- [4- [α- (1H- tetrazol-5-yl) benzyloxy] -3,5-dimethoxybenzyl] benzimidazole semihydrate

Prepared analogously to Example 57g from 2-n-propyl-4-methyl-6- (2,3-dimethylsuccinimino) -1- [4- [α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3.5 -dimethoxybenzyl] benzimidazole and 85% formic acid in methylene chloride.
Yield: 74.6% of theory,
Melting point: 192-194 ° C
C₃₄H₃₇N₇O₅ × 0.5 H₂O (632.71)
Calc .: C 64.54 H 6.05 N 15.50
Found: C 64.46 H 6.10 N 15.25

Example 95 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] -3,5-dibromobenzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3,5-dibromobenzyl] benzimidazole and 85% formic acid in methylene chloride.
Yield: 21.6% of theory,
Melting point: 132-134 ° C
C₃₄H₃₀Br₂N₈O (726.47)
Calc .: C 56.21 H 4.16 N 15.42 Br 21.99
Found: C 56.53 H 4.50 N 15.42 Br 22.03

Example 96 2-n-butyl-5-dimethylaminocarbonylamino-1- [4- [α- (1H-tetrazole- 5-yl) benzyloxy] -3-methoxybenzyl] benzimidazole

Prepared analogously to Example 57g from 2-n-butyl-5-dimethylaminocarbonylamino-1- [4 - [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] -3-methoxybenzyl] benzimidazole and 4N hydrochloric acid in ethanol .
Yield: 88.2% of theory,
Melting point: 181-185 ° C
C₃₀H₃₄N₈O₃ (554.66)
Calc .: C 64.96 H 6.18 N 20.20
Found: C 65.18 H 5.92 N 19.97

Example 97 5,7-dimethyl-2-ethyl-3- [4- [α- (O-ethyl-phosphono) benzyloxy] - benzimidazo [4,5-b] pyridine sodium salt semihydrate

Prepared analogously to Example 73b from 5,7-dimethyl-2-ethyl-3- [4- [α- (O, O-diethylphosphono) benzyloxy] benzyl] imidazo [4,5-b] pyridine and potassium hydroxide in methanol.
Yield: 52% of theory,
Melting point: from 150 ° C (decomp.)
C₂₆H₃₀N₄NaO₃P × 0.5 H₂O (509.52)
Calc .: C 61.29 H 6.33 N 11.00
Found: C 60.95 H 6.34 N 10.98

Example 98 2-n-propyl-4-methyl-1- [4- [α- (O-ethyl-phosphono) -N-methyl- benzylamino] benzyl] benzimidazole semihydrate a) 2-n-Propyl-4-methyl-1- [4- [α- (O, O-diethylphosphono) - N-methyl-benzylamino] benzyl] benzimidazole

1.1 g (2 mmol) of 2-n-propyl-4-methyl-1- [4- [α- (O, O-diethylphosphono) benzylamino] benzyl] benzimidazole are dissolved in 1 ml of formic acid and mixed with 2 ml of a 37% formalin solution added. The mixture is stirred at 100 ° C. for 2 hours, cooled and poured onto ice. After adding conc. Ammonia is extracted twice with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution and dried over magnesium sulfate. The organic phase is evaporated in vacuo and the residue obtained is purified on a silica gel column (particle size: 0.063-0.02 mm, ethyl acetate / petroleum ether = 1: 1 to 1: 2). The uniform fractions are combined and concentrated in vacuo.
Yield: 0.60 g (58% of theory),
R _f value: 0.45 (silica gel; mobile phase: petroleum ether / ethyl acetate = 1: 1)

b) 2-n-propyl-4-methyl-1- [4- [α- (O-ethyl-phosphono) -N-methyl- benzylamino] benzyl] benzimidazole semihydrate

Prepared analogously to Example 73b from 2-n-propyl-4-methyl-1- [4- [α- (O, O-diethylphosphono) -N-methyl-benzylamino] benzyl] benzimidazole and potassium hydroxide in methanol.
Yield: 77% of theory,
Melting point: from 106 ° C (decomp.)
C₂₈H₃₄N₃O₃P × 0.5 H₂O (500.59)
Calc .: C 67.18 H 7.05 N 8.40
Found: C 67.25 H 7.02 N 8.42

Example 99 2-n-propyl-4-methyl-1- [4- [α- (O-ethylphosphono) benzylamino] - benzyl] benzimidazole hydrobromide

0.5 g (1.0 mmol) of 2-n-propyl-4-methyl-1- [4- [α- (O, O-diethylphosphono) benzylamino] benzyl] benzimidazole are dissolved in 10 ml of 48% hydrobromic acid dissolved and heated to reflux for 5 hours. After cooling to room temperature, the pH is adjusted to 6 by adding concentrated ammonia and glacial acetic acid. The precipitate formed is filtered off and dried at 40 ° C over potassium hydroxide.
Yield: 47% of theory,
Melting point: from 140 ° C (decomp.)
C₂₅H₂₈N₃O₃P × HBr (530.42)
Calc. C 56.61 H 5.51 N 7.92
Found: C 56.48 H 5.80 N 8.05

Example 100 2-n-propyl-4-methyl-1- [4 - [(α-methanesulfonylaminocarbonyl) - benzyloxy] benzyl] benzimidazole

410 mg (1 mmol) of 2-n-propyl-4-methyl-1- [4 - [(α- (carboxy) benzyloxy] benzyl] benzimidazole are dissolved in 100 ml of thionyl chloride, a drop of dimethylformamide is added and the mixture is refluxed for 1 hour After the addition of toluene, the mixture is evaporated to dryness and taken up in 30 ml of acetone, and 1 ml of triethylamine and 150 mg (1.58 mmol) of methanesulfonic acid amide are stirred for 2 hours at room temperature, then the reaction mixture is concentrated and the residue is evaporated a silica gel column (particle size: 0.063 to 0.02 mm; methylene chloride / ethanol = 50: 1, 19: 1, 9: 1 and 4: 1) was purified, the uniform fractions were combined, evaporated and the residue obtained was triturated with ether and dried .
Yield: 15.3% of theory,
Melting point: 139-141 ° C
C₂₇H₂₉N₃O₄S (491.60)
Calc .: C 65.95 H 5.94 N 8.54
Found: C 65.67 H 6.27 N 8.89

Example 101 2-ethyl-4-methyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6- (n- butanesultam-1-yl) benzimidazole

Prepared analogously to Example 1b from 2-ethyl-4-methyl-1- [4- [(α-ethoxycarbonyl) benzyloxy] benzyl] -6- (n-butanesultam-1-yl) - benzimidazole and 2N sodium hydroxide solution in ethanol.

Example 102 2-ethyl-4-methyl-1- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] - 6- (n-butanesultam-1-yl) benzimidazole

Prepared analogously to Example 57g from 2-ethyl-4-methyl-1- [4- [(α- (N-triphenylmethyl) tetrazol-5-yl) benzyloxy] benzyl] -6- (n-butanesultam-1-yl) benzimidazole and 4N hydrochloric acid in ethanol.

Example 103 2-n-butyl-1- [4- [α- (ethoxycarbonyl) -α- (2-pyridyl) methyloxy] benzyl] - 6- (N-cyclohexylaminocarbonyl-methylamino) benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-1- (4-hydroxybenzyl) - 6- (N-cyclohexylaminocarbonyl-methylamino) -benzimidazole and α-bromo-pyridyl-2-acetic acid ethyl ester.
Yield: 90.0% of theory,
R _f value: 0.70 (silica gel; ethyl acetate / ethanol / ammonia = 90: 10: 1)
C₃₃H₄₄N₅O₄ (574.76)
Calc .: C 70.20 H 7.40 N 11.69
Found: C 69.97 H 7.26 N 11.21

Example 104 2-n-butyl-3- [4 - [(α-carboxy) benzyloxy] -3-methoxybenzyl] - 5-methyl-6-dimethylaminocarbonylamino-imidazo [4,5-b] pyridine

Prepared analogously to Example 1b from 2-n-butyl-3- [4 - [(α-ethoxycarbonyl) benzyloxy] -3-methoxybenzyl] -5-methyl-6-dimethylaminocarbonylaminoimidazo [4,5-b] pyridine and 2N sodium hydroxide solution in ethanol.
Yield: 91.8% of theory,
Melting point: 174-176 ° C
R _f value: 0.60 (silica gel; ethyl acetate / ethanol / ammonia = 50: 45: 5)
C₃₀H₃₅N₅O₅ (545.65)
Calc .: C 66.04 H 6.47 N 12.84
Found: C 66.25 H 6.49 N 12.95

Example 105 2-n-butyl-1- [4- [α- (ethoxycarbonyl) -α- (2-pyridyl) methyloxy] benzyl] - 6-dimethylaminocarbonylamino-benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-3- (4-hydroxybenzyl) -5-dimethylaminocarbonylamino-benzimidazole and ethyl α-bromo-pyridyl-2-acetic acid.
Yield: 87.5% of theory,
R _f value: 0.50 (silica gel; ethyl acetate / ethanol / ammonia = 90: 10: 1)
C₃₀H₃₅N₅O₄ (529.65)
Calculated: C 68.03 H 6.66 N 13.22
Found: C 68.09 H 6.83 N 13.06

Example 106 2-n-butyl-1- [4- [α- (ethoxycarbonyl) -α- (2-pyridyl) methyloxy] benzyl] - 6-cyclohexylcarbonylamino-benzimidazole

Prepared analogously to Example 1a from 2-n-butyl-1- (4-hydroxybenzyl) 6-cyclohexylcarbonylamino-benzimidazole and ethyl α-bromopyridyl-2-acetic acid.
Yield: 75.3% of theory,
R _f value: 0.50 (silica gel; ethyl acetate / ethanol / ammonia = 90: 10: 1)
C₃₄H₄₀N₄O₄ (568.73)
Calc .: C 71.80 H 7.09 N 9.35
Found: C 71.82 H 7.21 N 9.83

Example 107 2-n-butyl-3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] -3-methoxybenzyl] - 5-methyl-6-dimethylaminocarbonylamino-imidazo [4,5-b] pyridine

Prepared analogously to Example 57g from 2-n-butyl-3- [4- [α- (N- triphenylmethyl-tetrazol-5-yl) benzyloxy] -3-methoxybenzyl] -5-methyl-6-dimethylaminocarbonylamino-imidazo [4, 5-b] pyridine and 4N hydrochloric acid in ethanol.
Yield: 60.0% of theory,
Melting point: 197-199 ° C
R _f value: 0.60 (silica gel; ethyl acetate / ethanol / ammonia = 50: 45: 5)
C₃₀H₃₅N₉O₃ (569.68)
Calc .: C 63.25 H 6.19 N 22.13
Found: C 62.94 H 6.13 N 21.87

In the following pharmaceutical application examples Any suitable compound of the formula I, in particular the compounds A to I of the pharmacological Test report are used:

Example I

Ampoules containing 50 mg of active ingredient per 5 ml Active ingredient | 50 mg KH₂PO₄ 2 mg Na₂HPO₄ × 2H₂O 50 mg NaCl 12 mg Water for injections, ad 5 ml

Manufacturing

The buffer substances and the isotonans solved. The active ingredient is added and after complete solution with water to the nominal volume replenished.

Example II

Ampoules containing 100 mg of active ingredient per 5 ml Active ingredient | 100 mg Methylglucamine 35 mg Glycofurol 1000 mg Polyethylene glycol-polypropylene glycol block polymer 250 mg Water for injections, ad 5 ml

Manufacturing

Methylglucamine is dissolved in part of the water and the Active substance brought into solution with stirring and heating. To Add the solvent with water to the nominal volume replenished.

Example III

Tablets containing 50 mg of active ingredient Active ingredient | 50.0 mg Calcium phosphate 70.0 mg Milk sugar 40.0 mg Cornstarch 35.0 mg Polyvinyl pyrrolidone 3.5 mg Magnesium stearate 1.5 mg 200.0 mg

Manufacturing

The active ingredient, CaHPO₄, milk sugar and corn starch evenly moistened with an aqueous PVP solution. The Mass is passed through a 2 mm sieve, in a forced air drying cabinet dried at 50 ° C and sieved again.

After the lubricant has been mixed in, the granules are opened a tablet machine.

Example IV

Dragees containing 50 mg of active ingredient Active ingredient | 50.0 mg Lysine 25.0 mg Milk sugar 60.0 mg Cornstarch 34.0 mg gelatin 10.0 mg Magnesium stearate 1.0 mg 180.0 mg

Manufacturing

The active ingredient is mixed with the excipients and with moistened with an aqueous gelatin solution. After screening and Drying, the granules are mixed with magnesium stearate and pressed into cores.

The cores produced in this way are produced using known processes covered with an envelope. The coating suspension or solution dye can be added.

Example V

Dragees containing 100 mg of active ingredient Active ingredient | 100.0 mg Lysine 50.0 mg Milk sugar 86.0 mg Cornstarch 50.0 mg Polyvinyl pyrrolidone 2.8 mg Microcrystalline cellulose 60.0 mg Magnesium stearate 1.2 mg 350.0 mg

Manufacturing

The active ingredient is mixed with the excipients and with moistened with an aqueous PVP solution. The damp mass is passed through a 1.5 mm sieve and dried at 45 ° C. After drying, it is sieved again and the magnesium stearate added. This mixture is pressed into cores.

The cores produced in this way are produced using known processes covered with an envelope. The coating suspension or solution dyes can be added.

Example VI

Capsules containing 250 mg of active ingredient Active ingredient | 250.0 mg Cornstarch 68.5 mg Magnesium stearate 1.5 mg 320.0 mg

Manufacturing

The active ingredient and corn starch are mixed in and mixed with water moistened. The moist mass is sieved and dried. The dry granules are sieved and with magnesium stearate mixed. The final mix is sized in hard gelatin capsules 1 bottled.

Example VII

Oral suspension containing 50 mg of active ingredient per 5 ml Active ingredient | 50.0 mg Hydroxyethyl cellulose 50.0 mg Sorbic acid 5.0 mg Sorbitol 70% 600.0 mg Glycerin 200.0 mg Aroma 15.0 mg Water, ad 5.0 ml

Manufacturing

Distilled water is heated to 70 ° C. In here Dissolved hydroxyethyl cellulose with stirring. By adding Sorbitol solution and glycerin is cooled to room temperature. At room temperature, sorbic acid, aroma and active ingredient admitted. The suspension is vented with stirring evacuated. A dose = 50 mg is contained in 5.0 ml.

Example VIII

Suppositories containing 100 mg of active ingredient Active ingredient | 100.0 mg Adeps solidus 1600.0 mg 1700.0 mg

Manufacturing

The hard fat is melted. At 40 ° C the ground Active substance homogeneously dispersed in the melt. It will cooled to 38 ° C and in weakly pre-cooled suppository forms poured out.

Claims (15)

1. Phenylalkyl derivatives of the general formula in the
n is the number 0 or 1,
A is a straight-chain or branched alkylene group,
B is an oxygen atom, a carbonyl, hydroxymethylene, sulfenyl, sulfinyl or sulfonyl group, a straight-chain or branched alkylene group, an alkylidene group having 2 to 4 carbon atoms, a 1,1-cycloalkylene group or one optionally by an alkyl group or by an alkanoyl group 1 to 4 carbon atoms substituted imino group,
R _{a is} a chlorine or bromine atom, a hydroxyl, alkylsulfonyloxy, phenylsulfonyloxy or phenylalkylsulfonyloxy group or a group of the formula in which
one of the radicals D₁, D₂ or D₃ is a methylene or imino group and the remaining radicals of the radicals D₁ to D₃ are each methine groups, it being possible for one methine group to be replaced by a nitrogen atom and one of the methine groups to be replaced by the radical R₅ and optionally another of the methine groups the radical R₄ can be substituted,
zero, one or two of the radicals D₄, D₅, D₆ or D₇ a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each methine groups, it being possible for one methine group to be additionally substituted by the radical R₄ and a further methine group to be substituted by the radical R₅,
E is a carbon-carbon bond, an oxygen or sulfur atom, a hydroxymethylene or carbonyl group or one optionally by an alkyl group having 1 to 6 carbon atoms, by a cycloalkyl group, by an alkanoyl group having 2 to 5 carbon atoms, by an allyl or phenyl imino group substituted by benzyl group,
X represents an oxygen or sulfur atom or an imino group optionally substituted by an alkyl, phenyl or phenylalkyl group,
R₁ is a straight-chain or branched alkyl group having 1 to 9 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, the abovementioned saturated and unsaturated alkyl parts each being represented by a cycloalkyl group, by a fluorine, chlorine or bromine atom, can be substituted by a hydroxy, amino, alkylamino, dialkylamino or α, α-difluoroethane group, a perfluoroalkyl group having 1 to 4 carbon atoms or a cycloalkyl group which can be mono- or disubstituted by a trifluoromethyl group or an alkyl group,
R₂ is a hydrogen, fluorine, chlorine or bromine atom, an alkyl or perfluoroalkyl group each having 1 to 5 carbon atoms, a cyano or nitro group,
R₃ is a hydrogen atom, a cyano group, an alkyl group with 1 to 6 carbon atoms optionally substituted by a hydroxy or alkoxy group, a perfluoroalkyl group with 1 to 6 carbon atoms, an alkenyl group with 3 to 6 carbon atoms optionally substituted by fluorine atoms, a phenylalkyl or phenylalkenyl group with 2 up to 4 carbon atoms in the alkenyl part, an alkyl group with 1 to 5 carbon atoms, which are terminated by an imidazol-1-yl, triazolyl, tetrazolyl, phthalimido-, Ro-COO-, R-S-, R₇SO-, R₇SO₂-, R₇CO-, R₇NHCOO -, R₇NHCO, R₇NHCONR₇, R₈CONR₇ or R₈SO₂NR₇ group is substituted, wherein
the triazolyl group can additionally be mono- or disubstituted with an acetoxy or alkyl group and
R₆ is an alkyl or perfluoroalkyl group each having 1 to 8 carbon atoms, a cycloalkyl, phenyl, benzyl, phenylethyl, adamantyl, naphthyl, naphthylmethyl or naphthylethyl group,
R₇ has a hydrogen atom and the meanings mentioned above for R₆,
R₈ has the meanings mentioned above for R₇ and represents a piperazino group which is optionally substituted in the 4-position by an alkyl or phenyl group, a pyrrolidino, piperidino, hexamethyleneimino, morpholino, R₇O or (R₇) ₂N group,
R₄ is a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl group, a cycloalkyl group, an alkyl group substituted by 1, optionally substituted by a cycloalkyl group, by a hydroxy, alkoxy, alkylamino, dialkylamino, alkoxycarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group up to 6 carbon atoms and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl or perfluoroalkyl group each having 1 to 6 carbon atoms, an alkenyl or alkynyl group each having 2 to 6 carbon atoms, the above-mentioned alkyl and alkenyl parts in each case being substituted by a heteroaryl, hydroxyl, alkoxy, amino, Alkylamino, dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, piperidinocarbonyl, morpholinocarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, tetrazol-5-yl-5-tetra -yl-aminocarbonyl, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylaminocarbonyl, heteroarylaminosulfonyl or alkylcarbonylaminosulfonyl group may be mono- or disubstituted
an alkoxy group having 1 to 7 carbon atoms which is substituted in the 2-, 3-, 4-, 5-, 6- or 7-position by an imidazolyl, tetrazolyl, benzimidazolyl or tetrahydrobenzimidazolyl group, or a phenylalkoxy group,
an alkylsulfonyloxy group with 1 to 4 carbon atoms, a benzenesulfonyloxy or phenylalkanesulfonyloxy group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, in which the acyl radical is an alkanoyl group having 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, the above-mentioned phenyl nuclei each being represented by a fluorine, chlorine or bromine atom , mono- or disubstituted by a methyl or methoxy group and the substituents can be the same or different,
a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, where a carbonyl group in a phthalimino group can be replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group can be substituted by one or two alkyl groups , and additionally the phenyl nuclei mentioned above are mono- or disubstituted by alkyl or alkoxy groups, where the substituents can be the same or different and, at the same time, can be fully or partially hydrogenated,
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, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a bicycloalkane-2,3-dicarboxylic acid imino or bicycloalkene-2,3-dicarboxylic acid imino group in which the bicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms, can be substituted by 1, 2 or 3 methyl groups and an endomethylene group can be replaced by an oxygen atom,
a glutaric acid imino group in which the n-propylene group can be perfluorinated, can be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group,
a maleimide group optionally mono- or disubstituted by an alkyl or phenyl group, where the substituents can be identical or different,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms or by a cycloalkyl group,
a pyrrolidine, piperidine or pyridine ring bonded via a carbon atom, where a phenyl radical is fused to the pyridine ring via two adjacent carbon atoms and a methylene group adjacent to the N atom in a pyrrolidine or piperidine ring can be replaced by a carbonyl group,
an imidazolidinedione group optionally substituted by an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group,
a pyridazin-3-one or dihydro-pyridazin-3-one group which can be substituted in the 2-position by an alkyl group optionally substituted by a phenyl group and in the carbon skeleton additionally by 1 or 2 alkyl groups, or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 8 carbon atoms or phenylalkyl group,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 8 carbon atoms, an alkenyl group with 3 to 5 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
one of the radicals R₉, R₁₀ or R₁₁ also a bicyclohexyl or biphenylyl group or
R₁₀ and R₁₁ together with the intermediate nitrogen atom, a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group or
R₉ and R₁₁ together represent an alkylene group with 2 to 4 carbon atoms,
R _b is cyano, carboxy, Trifluormethylcarbonylamino-, Trifluormethylcarbonylaminomethyl-, Trifluormethylsulfonylamino-, Trifluormethylsulfonylaminomethyl-, alkylsulfonylamino, Alkylsulfonylaminomethyl-, arylsulfonylamino, Arylsulfonylaminomethyl-, Arylsulfonylaminocarbonyl-, Benzylsulfonylaminocarbonyl-, sulfonated, aminosulfonyl, alkylaminosulfonyl, Aralkylaminosulfonyl- , Arylaminosulfonyl-, alkylcarbonylaminosulfonyl-, aralkylcarbonylaminosulfonyl-, arylcarbonylaminosulfonyl-, sulfomethyl-, aminosulfonylmethyl-, alkylaminosulfonylmethyl-, aralkylaminosulfonylaminomethyl-, arylaminosulfonylmethyl-, alkylcarbonylaminosulfonylmethyl, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, alkylcarbonylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl-, arylaminosulfonylmethyl, -phosphino-, O-aryl-phosphino-, phosphono-, O-alkyl-phosphono-, O-aralkylphosphono-, O-aryl-phosphono-, O, O-dialkylphosphono-, phosphonomethyl-, O-alkyl-phosphono -methyl-, O-aralkyl-phosphonomethyl-, O-aryl-phosphono-methyl-, O, O-dialkylph osphonomethyl, phosphato, O-alkyl-phosphato, O-aralkyl-phosphato, O-aryl-phosphato or O, O-dialkoxy-phosphoryl group, optionally by an alkyl, trifluoromethyl, phenylalkyl or Triphenylmethyl group substituted 1H-tetrazolyl, 1H-tetrazolylalkyl, 1H-tetrazolylaminocarbonyl or triazolyl group, an alkylsulfonylaminocarbonyl or perfluoroalkylsulfonylaminocarbonyl group each having 1 to 6 carbon atoms in the alkyl part, an alkoxycarbonyl group, a total of 2 to 7 carbonyloxy carbonyl groups, an aroxycarbonyl group with a total of 2 to 7 carbonyloxy carbonyl groups -, ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl, cyclohexyloxycarbonylmethoxycarbonyl or (1,3-dioxa-2-oxo-4-methyl-cyclopenten-5-yl) methoxycarbonyl group,
R _{c is} a hydrogen atom, an alkyl, aralkyl, aryl, carboxy or alkoxycarbonyl group,
R _{d is} a straight-chain or branched alkyl chain having 1 to 10 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 10 carbon atoms, a cycloalkyl or cycloalkylalkyl group, one optionally by fluorine, chlorine or bromine atom, by methyl or methoxy groups mono- or disubstituted phenyl group, a biphenyl, naphthyl or heteroaryl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino or 2-carboxyphenylmethylamino group, where a carbonyl group in a phthalimino group is replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group can be substituted by one or two alkyl groups , and additionally the phenyl nuclei mentioned above are mono- or disubstituted by alkyl or alkoxy groups, where the substituents can be the same or different and, at the same time, can be fully or partially hydrogenated,
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, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a bicycloalkane-2,3-dicarboxylic acid imino or bicycloalkene-2,3-dicarboxylic acid imino group in which the bicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms, can be substituted by 1, 2 or 3 methyl groups and an endomethylene group can be replaced by an oxygen atom,
a glutaric acid imino group in which the n-propylene group can be perfluorinated, can be substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group,
a maleimide group optionally mono- or disubstituted by an alkyl or phenyl group, where the substituents can be the same or different,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms or by a cycloalkyl group, or
a pyrrolidine, piperidine or pyridine ring bonded via a carbon atom, where a phenyl radical is fused to the pyridine ring via two adjacent carbon atoms and a methylene group adjacent to the N atom in a pyrrolidine or piperidine ring can be replaced by a carbonyl group,
an imidazolidinedione group optionally substituted by an alkyl, phenylalkyl, tetramethylene, pentamethylene or hexamethylene group,
a pyridazin-3-one or dihydro-pyridazin-3-one group which can be substituted in the 2-position by an alkyl group optionally substituted by a phenyl group and in the carbon skeleton additionally by 1 or 2 alkyl groups, or
represents a R₁₁-NR₁₀-CO-NR₉ group in which R₉, R₁₀ and R₁₁ are as defined above,
also mean fluorine, chlorine or bromine atoms, alkyl or alkoxy groups,
their isomer mixtures, their tautomers, their enantiomers and their salts with inorganic or organic acids or bases,
unless otherwise mentioned,
the alkyl, alkylene or alkoxy parts mentioned above can each contain 1 to 4 carbon atoms and the cycloalkyl parts can each contain 3 to 7 carbon atoms, and
under "an aryl group" one optionally by a fluorine, chlorine or bromine atom, by a hydroxy, alkyl, alkoxy, phenylalkoxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano -, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group, mono- or disubstituted phenyl group, where the alkyl part can each contain 1 to 4 carbon atoms, or one and
under "a heteroaryl group" a 5-membered heteroaromatic ring which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or an imino group and 2 or 3 nitrogen atoms, and a 6-membered heteroaromatic ring which 1, Contains 2 or 3 nitrogen atoms, the rings mentioned above additionally by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino , Cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl group can be understood to be mono- or disubstituted. 2. phenylalkyl derivatives of the general formula I according to claim 1, in which R _a to R _f , A, B and n are defined with the proviso as mentioned in claim 1 above that
D₄ to D₇ with the additional provisions (a) to (j) represent methine groups or
D₇ represents a nitrogen atom and the radicals D₄, D₅ and D₆ with the additional provisos (a) to (g) and (k) to (m) or (a) to (g) and (n) to (p) methine groups or
one of the residues D₄, D₅ or D₆ represents a nitrogen atom and the remaining residues of the residues D₄ to D₆ and D₇ represent methine groups or
two of the residues D₄ to D₇ represent nitrogen atoms and the remaining residues of the residues D₄ to D₇ represent methine groups,
with the additional proviso that either

• (a) n represents the number 1 or
• (b) E with the exception of the carbon-carbon bond has the meanings mentioned above for E or
• (c) A, with the exception of the methylene group, has the meanings mentioned above for A or
• (d) B, with the exception of the oxygen atom, has the meanings mentioned above for B or
• (e) R _b, with the exception of the carboxyl group, has the meanings mentioned above for R _b or
• (f) R _c, with the exception of the hydrogen atom, has the meanings mentioned above for R _c or
• (g) R _d, with the exception of the phenyl group, has the meanings mentioned above for R _d or
• (h) R₁ with the exception of the n-butyl group has the meanings mentioned above for R₁ or
• (i) R₄ with the exception of the methyl group in position 7 has the meanings mentioned above for R₄ or
• (j) R₅, with the exception of the hydrogen atom, has the meanings mentioned above for R₅, or that
• (k) R₁ with the exception of the ethyl group has the meanings mentioned above for R₁ or
• (l) R₄, with the exception of the methyl group in position 7, has the meanings mentioned above for R₄ or
• (m) R₅, with the exception of the methyl group in position 5, has the meanings mentioned above for R₅ or
• (n) R₁ with the exception of the n-propyl group for R₁ has the meanings mentioned above or
• (o) R₄, with the exception of the hydrogen atom, has the meanings mentioned above for R₄ or
• (p) R₅, with the exception of the hydrogen atom, has the meanings mentioned above for R₅ and

the remaining radicals have the meanings mentioned above,
where in addition one methine group mentioned in the abovementioned definitions of the radicals D₄ to D₇ can be substituted by the radical R₄ and another methine group mentioned in the abovementioned definition of the radicals D₄ to D₇ by the radical R₅,
their isomer mixtures, their tautomers, their enantiomers and their salts with inorganic or organic acids or bases. 3. phenylalkyl derivatives of the general formula I according to claim 1 with the exception of

• (i) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (ii) 2-n-propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine and
• (iii) 5,7-Dimethyl-2-ethyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine, in which

n is the number 0 or 1,
A is a straight-chain or branched alkylene group,
B is an oxygen atom, a straight-chain or branched alkylene group having 1 to 3 carbon atoms or an imino group optionally substituted by an alkyl group or by an alkanoyl group having 1 to 4 carbon atoms,
R _{a is} a group of the formula in which
zero, one or two of the radicals D₄, D₅, D₆ or D₇ a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each methine groups, it being possible for one methine group to be additionally substituted by the radical R₄ and a further methine group to be substituted by the radical R₅,
E is a carbon-carbon bond, an oxygen or sulfur atom or an imino group which is optionally substituted by an alkyl group having 1 to 4 carbon atoms,
X is an oxygen or sulfur atom,
R₁ is a straight-chain or branched alkyl group having 1 to 6 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, the abovementioned saturated and unsaturated alkyl parts each being represented by a fluorine, chlorine or bromine atom, by a hydroxy or amino group, or a cycloalkyl group with 3 to 6 carbon atoms,
R₂ is a hydrogen, fluorine, chlorine or bromine atom, an alkyl or perfluoroalkyl group each having 1 to 5 carbon atoms, a cyano or nitro group,
R₃ is a hydrogen atom, a cyano group, an alkyl group with 1 to 3 carbon atoms optionally substituted by a hydroxy or alkoxy group, a perfluoroalkyl group with 1 to 3 carbon atoms, an alkenyl group with 3 to 6 carbon atoms optionally substituted by fluorine atoms, an alkyl group with 1 to 3 carbon atoms which is terminally substituted by an R₆COO, R₇S, R₇SO, R₇SO₂, R₇CO, R₇NHCOO, R₇NHCO, R₇NHCONR₇, R₈CONR₇ or R₈SO₂NR₇ group, where
R₆ is an alkyl or perfluoroalkyl group each having 1 to 4 carbon atoms, a cycloalkyl, phenyl, benzyl or phenylethyl group,
R₇ has a hydrogen atom and the meanings mentioned above for R₆,
R₈ has the meanings mentioned above for R₇,
R₄ is a hydrogen, fluorine, chlorine or bromine atom, a trifluoromethyl group, a cycloalkyl group, an alkyl group which has 1 to 6 carbon atoms and is optionally substituted by a hydroxyl, alkoxy or alkoxycarbonyl group and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl or perfluoroalkyl group each having 1 to 6 carbon atoms, an alkenyl or alkynyl group each having 2 to 6 carbon atoms, the above-mentioned alkyl and alkenyl parts each being substituted by a heteroaryl, hydroxyl, alkoxy, amino, Alkylamino, dialkylamino, alkylcarbonylamino, N-alkyl-alkylcarbonylamino, carboxy, alkoxycarbonyl, alkylcarbonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or tetrazol-5-yl group can be mono- or disubstituted,
an alkoxy group with 1 to 5 carbon atoms,
an alkylsulfonyloxy group with 1 to 4 carbon atoms, a benzenesulfonyloxy or phenylalkanesulfonyloxy group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, in which the acyl radical is an alkanoyl group having 1 to 5 carbon atoms, an alkoxycarbonyl group having a total of 2 to 4 carbon atoms, one Alkylsulfonyl group having 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, the phenyl nuclei mentioned above each being mono- or disubstituted by a fluorine, chlorine or bromine atom, by a methyl or methoxy group and the substituents can be the same or different,
a phthalimino or homophthalimino group, it being possible for a carbonyl group in a phthalimino group to be replaced by a methylene, alkylmethylene or dialkylmethylene group and a methylene group in a homophthalimino group to be substituted by one or two alkyl groups, and in addition the above-mentioned phenyl nucleus by alkyl or alkoxy groups mono- or disubstituted, where the substituents can be the same or different and at the same time can be wholly or partly hydrogenated,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, wherein in addition the above-mentioned fused aromatic or heteroaromatic rings in the carbon structure by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxy, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms, or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 6 carbon atoms or phenylalkyl group,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 6 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
R₁₀ and R₁₁ together with the intermediate nitrogen atom, a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group or
R₉ and R₁₁ together represent an alkylene group with 2 to 4 carbon atoms,
R _{b is} a cyano-, carboxy-, arylsulfonylaminocarbonyl-, benzylsulfonylaminocarbonyl-, sulfo-, alkylcarbonylaminosulfonyl-, aralkylcarbonylaminosulfonyl-, arylcarbonylaminosulfonyl-, alkylcarbonylaminosulfonylmethyl-, aralkylcarbonylaminosulfonylmethyl-, phosphonylmethyl-, arylcarbonyl, methyl-, phosphonylmethyl-, arylcarbonyl -Alkyl-phosphono- O, O-dialkylphosphono-, phosphono-methyl, O-alkyl-phosphonomethyl, O, O-dioalkylphosphono-methyl, phosphato or O-alkyl-phosphato group, optionally by a phenylalkyl or triphenylmethyl group substituted 1H-tetrazolyl or 1H-tetrazolylalkyl group, an alkylsulfonylaminocarbonyl or perfluoroalkylsulfonylaminocarbonyl group each having 1 to 6 carbon atoms in the alkyl part, an alkoxycarbonyl group having a total of 2 to 7 carbon atoms or an aralkoxycarbonyl group,
R _{c is} a hydrogen atom, a methyl, phenyl, benzyl, carboxy or alkoxycarbonyl group and
R _{d is} a straight-chain or branched alkyl chain having 1 to 6 carbon atoms, a straight-chain or branched alkenyl or alkynyl group each having 2 to 6 carbon atoms, a cycloalkyl or cycloalkylalkyl group, one optionally by fluorine, chlorine or bromine atom, by methyl or mehoxy groups mono- or disubstituted phenyl group, a biphenyl, naphthyl or heteroaryl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a phthalimino or homophthalimino group, where a carbonyl group in a phthalimino group can be replaced by a methylene, alkylmethylene or dialkylmethylene group, and a methylene group in a homophthalimino group can be substituted by one or two alkyl groups, and in addition the above-mentioned phenyl nucleus by alkyl - or alkoxy groups mono- or disubstituted, where substituents can be the same or different and at the same time can be hydrogenated in whole or in part,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two alkyl groups or by a tetramethylene or pentamethylene group, in which a methylene group can be replaced by a carbonyl or sulfonyl group,
a 5-membered heteroaromatic ring bonded via a carbon atom or via an imino group, which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom, or a 6-membered heteroaromatic ring bonded via a carbon atom, the 1 or 2 Contains nitrogen atoms, where both the 5-membered and the 6-membered heteroaromatic rings each have an n-propylene, n-butylene or 1,3-butadienyl group via two adjacent carbon atoms or an n-propylene group via an imino group and an adjacent carbon atom, n-butylene or 1,3-butadienyl group is added and in a fused pyridine ring thus formed, a methine group through a nitrogen atom and a vinylene group in the 3-, 4-position to the nitrogen atom of the formed pyridine ring through a sulfur atom or in a fused phenyl ring thus formed one or two methine groups can be replaced by N atoms can, in addition, the above-mentioned fused aromatic or heteroaromatic rings in the carbon skeleton by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl, nitro, amino, alkylamino, dialkylamino, alkanoylamino, cyano, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, trifluoromethyl, alkanoyl, aminosulphonyl, alkylaminosulphonyl or dialkylaminosulfonyl mono substituted by fluorine or chlorine atoms, by methyl, methoxy or hydroxy may be disubstituted and an NH group which may be present in an imidazole ring may be substituted by an alkyl group having 1 to 6 carbon atoms, or
a R₁₁-NR₁₀-CO-NR₉ group in which R₉ to R₁₁ are defined as mentioned above,
also mean chlorine or bromine atoms, methyl or methoxy groups,
their isomer mixtures, their tautomers, their enantiomers and their salts with inorganic or organic acids or bases,
unless otherwise mentioned,
the alkyl, alkylene or alkoxy parts mentioned above can each contain 1 to 4 carbon atoms and the cycloalkyl parts can each contain 3 to 7 carbon atoms, and
"aryl group" means a phenyl group which is mono- or disubstituted, optionally by a fluorine, chlorine or bromine atom, by a hydroxyl, alkyl, alkoxy, phenylalkoxy, phenyl or nitro group, the alkyl part each containing 1 to 4 carbon atoms can, or a naphthyl group and
under "a heteroaryl group" a 5-membered heteroaromatic ring which contains an imino group, an oxygen or sulfur atom or an imino group and an oxygen, sulfur or nitrogen atom or an imino group and 2 or 3 nitrogen atoms, and a 6-membered heteroaromatic ring which 1, Contains 2 or 3 nitrogen atoms, where the rings mentioned above may additionally be understood to be mono- or disubstituted by a fluorine, chlorine or bromine atom, by an alkyl, alkoxy, hydroxyl, phenyl or nitro group. 4. phenylalkyl derivatives of the general formula I according to claim 1 with the exception of

• (i) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (ii) 2-n-propyl-7-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine and
• (iii) 5,7-Dimethyl-2-ethyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] imidazo [4,5-b] pyridine, in which

n is the number 0,
A is a methylene, ethylene or ethylidene group,
B an oxygen atom, a methylene, imino, methylimino or acetylimino group,
R _{a is} a group of the formula in which zero, one or two of the radicals D₄, D₅, D₆ or D₇ have a nitrogen atom and the remaining radicals D₄, D₅, D₆ or D₇ each have methine groups, a methine group being additionally substituted by the radical R₄ and a further methine group by the radical R₅ can,
E is a carbon-carbon bond,
R₁ is a straight-chain or branched alkyl group having 1 to 6 carbon atoms,
R₂ is a hydrogen, fluorine, chlorine or bromine atom,
R₃ is a hydroxyalkyl group with 1 or 2 carbon atoms,
R₄ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms and
R₅ is a hydrogen, fluorine, chlorine or bromine atom,
a straight-chain or branched alkyl group with 1 to 3 carbon atoms,
an amino or nitro group,
an acylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 5 carbon atoms, in which the acyl radical is an alkanoly group having 1 to 5 carbon atoms or a benzenesulfonyl group, the phenyl nucleus mentioned above being mono- or disubstituted by a methyl or methoxy group and the substituents being the same or can be different,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two methyl groups, in which a methylene group can be replaced by a carbonyl or sulfonyl group, or a phthalimino, homophthalimino or isoindolin-1-one-yl group,
a benzimidazol-2-yl group which is optionally substituted in the 1-position by an alkyl group having 1 to 3 carbon atoms or
a R₁₁-NR₁₀-CO-NR₉ group in which
R₉ is a hydrogen atom, an alkyl group with 1 to 5 carbon atoms or a phenylalkyl group with 1 to 3 carbon atoms in the alkyl part,
R₁₀ represents a hydrogen atom, an alkyl group with 1 to 5 carbon atoms or a cyclohexyl group,
R₁₁ is a hydrogen atom, a benzyl group or an alkyl group having 1 to 5 carbon atoms or
R₉ and R₁₁ together represent an alkylene group with 2 or 3 carbon atoms,
R _{b is} a carboxy, 1H-tetrazolyl or O-alkylphosphono- or alkylsulfonylaminocarbonyl group, each having 1 to 3 carbon atoms in the alkyl part,
R _{c is} a hydrogen atom or a phenyl group,
R _{d is} a straight-chain or branched alkyl chain with 1 to 4 carbon atoms, a cyclohexyl, cyclohexylmethyl, phenyl, biphenyl, methoxyphenyl, chlorophenyl, pyridyl or naphthyl group,
R _e and R _{f are} hydrogen atoms and if
R₅ is a benzimidazol-2-yl group which is optionally substituted in the 1-position by an alkyl group having 1 to 3 carbon atoms,
a 5-, 6- or 7-membered alkyleneimino group optionally substituted by one or two methyl groups, in which a methylene group can be replaced by a carbonyl or sulfonyl group, or
a R₁₁-NR₁₀-CO-NR₉ group in which R₉ to R₁₁ are defined as mentioned above,
also mean methoxy groups, chlorine or bromine atoms, their isomer mixtures, their tautomers, their enantiomers and their salts with inorganic or organic acids or bases. 5. The following compounds of general formula I according to claim 1:

• (a) 2-n-propyl-4-methyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (b) 2-n-butyl-1- [4 - [(α-carboxy) benzyloxy] benzyl] -6-dimethylaminocarbonylamino-benzimidazole,
• (c) 2-n-propyl-6- (1-methyl-benzimidazol-2-yl) -4-methyl-1- [4- [(α-carboxy) benzyloxy] benzyl] benzimidazole,
• (d) 2-methyl-4- [4 ′ - [(α-carboxy) benzyloxy] benzyloxy] quinoline,
• (e) 2-n-butyl-8-methyl-3- [4 - [(α-carboxy) benzyloxy] benzyl] quinazolion-4-one semihydrate,
• (f) 2-n-propyl-4-methyl-6- (1-methyl-benzimidazol-2-yl) -1- [4- [α- (1-tetrazol-5-yl) benzyloxybenzyl] benzimidazole,
• (g) 2-n-butyl-6- (N-propionyl-methylamino) -1- [4 - [(1-carboxy-3-methyl) butyloxy] benzyl] benzimidazole,
• (h) 2-n-Butyl-5-methyl-6- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) -pyrimmidinon-1-yl) -3- [4- [α- (1H-tetrazol-5-yl) benzyloxy] benzyl] - imidazole [4,5-b] pyridine and
• (i) 2-n-butyl-1- [4 - [(α- (α-ethylphosphono) benzylamino] benzyl] benzimidazole,

the salts thereof with inorganic or organic acids or Bases. 6. Physiologically acceptable salts of the compounds at least one of claims 1 to 5 with inorganic or organic acids or bases. 7. Medicament containing a compound according to at least one of claims 1 to 5 or a physiologically acceptable Salt according to claim 6 in addition to optionally one or several inert carriers and / or diluents. 8. Use of a connection according to at least one of the claims 1 to 6 for the manufacture of a medicament with an angiotensin antagonistic effect. 9. A method for producing a medicament according to claim 8, characterized in that on non-chemical A connection according to at least one of claims 1 to 6 in one or more inert carriers and / or diluents is incorporated. 10. A process for the preparation of the phenylalkyl derivatives according to claims 1 to 6, characterized in that

• a) a compound of the general formula R _a -H (II) in which R _{a is} as defined in claims 1 to 5, with a compound of the general formula in the
  A, B, n and R _c to R _{f are} as defined in claims 1 to 5 and
  Z₁ represents a nucleophilic leaving group, implemented and, if necessary, a compound thus obtained is hydrolyzed or
• b) a compound of the general formula in the
  R _a , R _e , R _f and A are as defined in claims 1 to 5,
  B 'is a straight-chain or branched alkylene group having 1 to 4 carbon atoms and
  Z₂ is a nucleophilic leaving group, with a compound of the general formula R _b , R _d and n are as defined in claims 1 to 5 and
  R _c 'represents an alkoxycarbonyl group, reacted and, if necessary, a compound thus obtained is hydrolyzed or hydrolyzed and decarboxylated or
• c) for the preparation of compounds of the general formula I in which B represents an oxygen or sulfur atom or an imino group optionally substituted by an alkyl group, a compound of the general formula in the
  R _a , R _e , R _f and A are as defined in claims 1 to 5 and
  B '' represents an oxygen or sulfur atom or an imino group optionally substituted by an alkyl group, with a compound of the general formula in the
  R _b to R _d and n are as defined in claims 1 to 5 and
  Z₃ represents a nucleophilic leaving group, implemented and, if necessary, a compound thus obtained is hydrolyzed or
• d) for the preparation of a compound of general formula I, in which R _{b represents} a carboxy group, a compound of general formula in the
  R _a , R _c to R _f , A, B and n are as defined in claims 1 to 5 and
  R _b 'represents a group which can be converted into a carboxy group by means of hydrolysis, thermolysis or hydrogenolysis, is converted into a corresponding carboxy compound or
• e) for the preparation of a compound of the general formula I in which R _{b represents} a 1H-tetrazolyl group, a protective radical of a compound of the general formula in the
  R _a , R _c to R _f , A, B and n are as defined in claims 1 to 5 and
  R _b ′ 'represents a 1H-tetrazolyl group protected in the 1- or 2-position by a protective radical, is split off or
• f) for the preparation of a compound of the general formula I in which R _{b represents} a 1H-tetrazolyl group, a compound of the general formula in which R _a , R _c to R _f , A, B and n are as defined in claims 1 to 5, is reacted with hydrochloric acid or its salts, or
• g) for the preparation of compounds of the general formula I in which R _{a is} a group of the formula represents a compound of the general formula in which D₁ to D₇ are as defined in claims 1 to 5, one of X₁ and Y₁ is a group of the general formula and the other of X₁ or Y₁ is a group of the general formula represent where
  R₁, A, B, E, n and R _b to R _{f are} as defined in claims 1 to 5,
  Z₄ and Z₅, which may be the same or different, optionally substituted amino groups or optionally substituted by lower alkyl groups or hydroxy or mercapto groups
  Z₄ and Z₅, together represent an oxygen or sulfur atom, an imino group optionally substituted by an alkyl group having 1 to 3 carbon atoms, an alkylenedioxy or alkylene dithio group each having 2 or 3 carbon atoms, is cyclized or
• h) for the preparation of compounds of general formula I, in which R₅ represents a R₁₁-NR₁₀-CO-NR₉ group, a compound of general formula in the
  R _b to R _f , A, B and n are as defined in claims 1 to 5 and
  R _a 'represents one of the radicals mentioned for R _a in claims 1 to 5, in which R₅ represents an amino group, an alkylamino group having 1 to 8 carbon atoms or a phenylalkylamino group having 1 to 4 carbon atoms in the alkyl part, with a compound of the formula in the
  R₁₀ represents a hydrogen atom, an alkyl group with 1 to 8 carbon atoms, an alkenyl group with 3 to 5 carbon atoms, a phenylalkyl group or a cycloalkyl group with 5 to 7 carbon atoms,
  R₁₁ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms or
  one of the radicals R₁₀ or R₁₁ is also a bicyclohexyl or biphenylyl group or
  R₁₀ and R₁₁ together with the intermediate nitrogen atom, a straight-chain alkyleneimino group having 4 to 6 carbon atoms or a morpholino group and
  Z₆ is a nucleophilic leaving group or also if one of the radicals R₁₀ or R₁₁ represents a hydrogen atom,
  Z₆ together with R₁₀ or R₁₁ represent a nitrogen-carbon bond, is implemented or
• i) for the preparation of compounds of the general formula I in which R₅ is an acylamino group which is optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, in which the acyl radical represents an alkanoyl group with 1 to 7 carbon atoms, an alkoxycarbonyl group with a total of 2 to 4 carbon atoms, an alkylsulfonyl group with 1 to 6 carbon atoms, a benzoyl, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanyl group, wherein the above-mentioned phenyl nuclei are each mono- or disubstituted by a fluorine, chlorine or bromine atom, by a methyl or methoxy group and the substituents may be the same or different, a compound of the formula in the
  R _b to R _f , A, B and n are as defined in claims 1 to 5 and
  R _a '' represents one of the radicals mentioned for R _a in claims 1 to 5,
  in which R₅ represents an amino group optionally substituted by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl, cycloalkylalkyl, bicyclohexyl or biphenyl group, with a compound of the formula HO-U-R₁₂ (XV) in the
  U is a carbonyl or sulfonyl group and
  R₁₂ is an alkyl group with 1 to 6 carbon atoms, an alkoxy group with 1 to 3 carbon atoms, a phenyl, phenylalkyl, naphthyl or cycloalkyl group or, if U represents a carbonyl group, is a hydrogen atom, the phenyl nuclei mentioned above each being represented by a fluorine -, Chlorine or bromine atom, mono- or disubstituted by a methyl or methoxy group and the substituents can be the same or different, or reacted with their reactive derivatives or
• j) for the preparation of compounds of the general formula I in which R _{b represents} a phosphono- or O-alkyl-phosphono group, a compound of the general formula in the
  A, B, R _a , R _c to R _f and n are as defined in claims 1 to 5 and
  R _b '''represents an O-alkyl or O, O-dialkyl-phosphono group, in which the alkyl part can each contain 1 to 5 carbon atoms, is hydrolyzed and

if desired, a compound of the general formula I thus obtained, in which R₂ or R₅ represents a nitro group, is converted by reduction into a corresponding compound of the general formula I, in which R₂ or R₅ represents an amino group, or
a compound of the general formula I thus obtained, in which B represents an imino group, can be converted by alkanoylation into a corresponding compound of the general formula I in which B represents an imino group substituted by an alkanoyl group having 1 to 4 carbon atoms, or
a compound of the general formula I obtained in this way, in which B represents an imino group, it can be converted by alkylation into a corresponding compound of the general formula I in which B represents an imino group substituted by an alkyl group having 1 to 3 carbon atoms, or
if necessary, a protective residue used during the reactions to protect reactive groups is split off and / or
if desired, an isomer mixture of a compound of the general formula I thus obtained is separated into its isomers of the enantiomers by means of isomer separation or
a compound of the general formula I thus obtained is converted into its salt, in particular for pharmaceutical use, into its physiologically compatible salt with an inorganic or organic acid or base.