DE4025358A1 - New bi:phenyl:methyl-substd. imidazole derivs. - Google Patents

Abstract

Biphenylylmethyl-imidazole derivs. (I) and their 1- and 3-isomer mixtures and addn. and base salts are new. Where A1-A4 = H or CH and one or two = N; r1 = H; F; Cl; Br; OH; 1-3C alkyl; 1-3C alkoxy; amino opt. mono- or disubstd. by 1-6C alkyl, phenyl, 5-7C cycloalkyl, phenyl-1-3C alkyl or 5-7C cycloalkyl-1-3C alkyl; acylamino opt. 3-, 4-, 5-, 6- or 7-halo or hydroxy-substd. when acyl gp. is 1-7C alkanoyl; 2-4C alkoxycarbonyl; 1-6C alkanesulphonyl; benzoyl, benzenesulphonyl, 2-carboxy-cyclohexylcarbonyl, 2-aminocarbonyl-cyclohexylcarbonyl, 5-7C cycloalkylcarbonyl, phenyl-1-4C alkanoyl or 5-7C cycloalkyl-1-4C alkanoyl in which a phenyl gp, is opt. mono- or disubstd. by F, Cl, Br, CH3 or CH3O; a 3-5C alkylsultame gp.; pyrrolidino, piperidino or hexamethyleneimino opt. substd. by 1-3C alkyl, carboxyl-1-3C alkyl or oxo; opt. hydrogenated phthalimido or 2-oxo-isoindolin-1-yl; or -N(R6)-CO-N(R7)(R8); R2 = H or 1-3C alkyl; R3 = 1-6C alkyl; R4 = COOH, CN, 1H-tetrazolyl, 1-triphenylmethyl-tetrazolyl or 2-5C alkoxycarbonyl; R5 = H, F, Cl or Br; R6, R7 = H, 1-8C alkyl, 5-7C cycloalkyl, 5-7C cycloalkyl-1-3C alkyl or phenyl or phenyl-1-3C alkyl opt. mono- or disubstd. by OH or 1-3C alkoxy, or R6 + R7 = ethylene or propylene; R8 = H, 1-8C alkyl, 5-7C cycloalkyl, 5-7C cycloalkyl-1-3C alkyl, phenyl or phenyl-1-3C alkyl opt. mono- or disubstd. by OH or 1-3C alkoxy, 2-(Cl or Br)-ethyl, 3-(Cl or Br)-propyl or, when R6 + R7 = ethylene or propylene, also dialkylaminocarbonyl; except cpds. (I) where R1 = R2 = R5 = H, R3 = n-butyl, R4 = COOH and (i) one of A1-A4 = N and the remainder = CH, (ii) A2 and A4 or A1 and A3 = N and the remainder = CH, (iii) A4 = N, A3 = HO-C or CH3O-C and A1 = A2 = CH or (iv) A4 = N, A1 = CH3-C and A2 = A3 = CH.

Description

The present invention relates to heterocyclic Imidazoles of the general formula

their 1, 3-isomer mixtures, their tautomers, their enantiomers as well as their addition salts, especially for the pharmaceutical application whose physiologically acceptable Addition salts with inorganic or organic acids or Bases.

In the above general formula
one or two of the radicals A₁, A₂, A₃ or A₄ is a nitrogen atom and the remaining radicals A₁, A₂, A₃ or A₄ each have a methine group,
R₁ is a hydrogen, fluorine, chlorine or bromine atom, a hydroxy, alkyl or alkoxy group, optionally substituted on the nitrogen atom by an alkyl group of 1 to 6 carbon atoms, mono- or by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group disubstituted amino group wherein the substituents may be the same or different, or mono-substituted N-acylamino group in which the acyl group is an alkanoyl group having 1 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 4 carbon atoms in total, an alkylsulfonyl group having 1 to 6 carbon atoms, a Benzoyl, benzenesulphonyl, phenylalkanesulphonyl, naphthalenesulphonyl, 2-carboxycyclohexylcarbonyl, 2-aminocarbonylcyclohexylcarbonyl, cycloalkylcarbonyl, phenylalkanoyl or cycloalkylalkanoyl group, the abovementioned phenyl nuclei being represented by a fluorine, chlorine or bromine atom, mono- or disubstituted by a methyl or methoxy group and the substituents equal o which may be different, a Alkylsultamgruppe having 3 to 5 carbon atoms in the alkyl moiety, optionally substituted by an alkyl or Hydroxycarbonylalkylgruppe pyrrolidino, piperidino or Hexamethyleniminogruppe, a pyrrolidinone, piperidinone or Hexamethyleniminongruppe, an optionally completely or partially hydrogenated phthalimido or a Group of formula

in which
R₆, R₇ and R₈, which may be the same or different, are hydrogen atoms, alkyl groups having 1 to 8 carbon atoms, cycloalkyl, phenyl, cycloalkylalkyl or phenylalkyl groups or
R₇ is also a 2-chloro-ethyl, 2-bromo-ethyl, 3-chloro-propyl or 3-bromo-propyl group or
R₆ and R₇ together represent an ethylene or propylene group, wherein the phenyl nucleus of the above-mentioned phenyl and phenylalkyl groups may be mono- or disubstituted by hydroxy or alkoxy groups and the substituents may be the same or different and, unless otherwise stated, those above each of the alkyl and alkoxy moieties mentioned may contain from 1 to 3 carbon atoms, the alkanoyl moieties may contain from 1 to 4 carbon atoms and the cycloalkyl moieties may each contain from 5 to 7 carbon atoms,
R₂ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms,
R₃ is an alkyl group having 1 to 6 carbon atoms,
R₄ is a carboxy, cyano, 1H-tetrazolyl or 1-triphenylmethyl-tetrazolyl group or an alkoxycarbonyl group having a total of 2 to 5 carbon atoms and
R₅ is a hydrogen, fluorine, chlorine or bromine atom.

The new compounds of the above formula I have valuable Properties on. Thus, the compounds of the formula I, in the R₄ an alkoxycarbonyl group, a carboxy or 1H-tetrazolyl group means, in particular, valuable pharmacological Properties on, as these angiotensin II antagonists represent.

The subject matter of the present invention is therefore the new, above-mentioned heterocyclic imidazoles, wherein the corresponding cyano, alkoxycarbonyl and triphenylmethyl compounds also represent valuable intermediates.

Another object of the present invention are thus new drugs, which are one of the pharmacological mentioned above active compounds of general formula I or a corresponding physiologically acceptable addition salt and especially for the treatment of hypertension and Cardiac insufficiency, further for the treatment of ischemic peripheral Circulatory disorders, myocardial ischemia (Angina), for the prevention of heart failure progression Myocardial infarction, for the treatment of diabetic nephropathy,  of glaucoma, gastrointestinal diseases and Bladder disorders are suitable.

For the definition in the definition by the radicals A₁, A₂, A₃ and A₄ mentioned above heteroaromatic radicals is the pyrido, pyrimido, pyrazino or pyridazino group, for R₁ that of the hydrogen, fluorine, chlorine or bromine atom, the methyl , Ethyl, n-propyl, isopropyl, hydroxy, methoxy, ethoxy, n-propoxy, isopropoxy, formylamino, acetylamino, propionylamino, n-butanoylamino, isobutanoylamino, n-pentanoylamino, , 2-methyl-n-butanoylamino, 3-methyl-n-butanoylamino, n-hexanoylamino, n-heptanoylamino, cyclopentylcarbonylamino, cyclohexylcarbonylamino, cycloheptylcarbonylamino, cyclopentylmethylcarbonylamino, cyclohexylmethylcarbonylamino, cycloheptylmethylcarbonylamino, (2 Cyclopentylethyl) - carbonylamino, (2-cyclohexylethyl) carbonylamino, (2-cycloheptylethyl) carbonylamino, benzoylamino, phenylacetylamino, 2-phenylpropionylamino, naphthyl- (1) - carbonylamino, naphthyl- (2-) carbonylamino, methoxycarbonylamino, ethoxycarbonylamino, n-propoxycarbony lino, methanesulfonylamino, ethanesulfonylamino, n-propanesulfonylamino, isopropanesulfonylamino, n-butanesulfonylamino, n-pentanesulfonylamino, n-hexanesulfonylamino, benzenesulfonylamino, 2-methylbenzenesulfonylamino, 4-methylbenzenesulfonylamino, 2-methoxybenzenesulfonylamino, 4-Methoxybenzenesulfonylamino, 2-fluorobenzenesulfonylamino, 4-fluorobenzenesulfonylamino, 2-chlorobenzenesulfonylamino, 4-chlorobenzenesulfonylamino, 2-bromobenzenesulfonylamino, 4-bromobenzenesulfonylamino, 2,4-dimethoxybenzenesulfonylamino, benzylsulfonylamino, naphthalene (1) sulfonylamino, naphthalene- (2) sulfonylamino, propylsultam- (1) -yl, n-butanesultam- (1) -yl, n-pentanesultam- (1) -yl, amino, methylamino, Ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, n-pentylamino, n-hexylamino, dimethylamino, diethylamino, di-n-propylamino, methylethylamino, methylisopropylamino -, methyl-n-butylamino, ethyl-n-propylamino, methyl-n-pentylamino, ethyl-n-hexylamino, cyclopentyl amino, cyclohexylamino, cycloheptylamino, cyclopentylmethylamino, cyclohexylmethylamino, cycloheptylmethylamino, (2-cyclopentylethyl) amino, (2-cyclohexylethyl) amino, (2-cycloheptylethyl) amino, (3-cyclopentylpropyl) -amino, (3-cyclohexylpropyl) amino, (3-cycloheptylpropyl) amino, benzylamino, 2-phenylethylamino, 3-phenylpropylamino, phenylamino, dicyclohexylamino, dicyclohexylmethylamino, dibenzylamino, N-methyl cyclopropylamino, N -methylcyclopentylamino, N-ethylcyclohexylamino, N- (n-propyl) -cycloheptylamino, N -methylcyclopentylmethylamino, N -ethylcyclohexylmethylamino, N- (n-propyl) -cycloheptylmethylamino, N-methyl- (2-cyclopentylethyl) amino, N-ethyl- (2-cyclohexylethyl) amino, N- (n-propyl) - (2-cycloheptylethyl) amino, N -methyl - (3-cyclopentylpropyl) amino, N-ethyl (3-cyclohexylpropyl) amino, N -methylbenzylamino, N-ethylbenzylamino, N-isopropylbenzylamino, N-methyl- (2 -phenylethyl) amino, N-methyl-phenylamino, N- (n-propyl) -phenylamino, N-acety 1-methylamino, N-acetyl-ethylamino, N-acetyl-isopropylamino, N-acetyl-n-butylamino, N-acetyl-n-hexylamino, N-propionyl-methylamino, N-propionyl-ethylamino , N-propionyl-n-butylamino, Nn-butanoyl-methylamino, Nn-butanoyl-ethylamino, Nn-butanoyl-n-pentylamino, N-isobutanoyl-methylamino, N-isobutanoyl-ethylamino, N-isobutanoyl -isopropylamino, N-isobutanoyl-n-butylamino, N-isobutanoyl-n-pentylamino, Nn-pentanoyl-methylamino, Nn-pentanoyl-ethylamino, Nn-pentanoyl-isopropylamino, Nn-pentanoyl-n-pentylamino -, Nn-hexanoyl-methylamino, Nn-hexanoyl-ethylamino, Nn-hexanoyl-isopropylamino, Nn-hexanoyl-n-pentylamino, N-cyclopentylcarbonyl-methylamino, N-cyclohexylcarbonyl-methylamino, N-cyclohexylcarbonyl-ethylamino -, N-cycloheptylcarbonyl-methylamino, N-cyclopentylmethylcarbonyl-methylamino, N-cyclohexylmethylcarbonyl-methylamino, N-cycloheptylmethylcarbonyl-methylamino, N- (2-cyclopentylethylcarbonyl) -methylamino, N- (2-cyclohexylethylcarbonyl) -methylamino -, N- (2- Cycloheptylethylcarbonyl) -methylamino, N-benzoyl-methylamino, N-benzoyl-ethylamino, N-benzoyl-isopropylamino, N-benzoyl-n-butylamino, N-benzoyl-n-pentylamino, N-benzyl-n -hexylamino, N-phenylacetyl-methylamino, N-naphthyl- (1) -carbonyl-methylamino, N-naphthyl- (2) -carbonyl-methylamino, N-methoxycarbonyl-methylamino, N-methoxycarbonyl-ethylamino , N-methoxycarbonyl-n-butylamino, N-methoxycarbonyl-isobutylamino, N-ethoxycarbonyl-methylamino, N-ethoxycarbonyl-ethylamino, N-ethoxycarbonyl-isopropylamino, N-ethoxycarbonyl-n-butylamino, Nn-propoxycarbonyl -methylamino, N-methanesulfonylmethylamino, N -ethanesulfonylisopropylamino, N- (n-propanesulfonyl) -methylamino, isopropanesulfonylamino, N- (n-butanesulfonyl) -methylamino, N- (n-pentanesulfonyl) -methylamino, N- (n-hexanesulfonyl) -methylamino, benzenesulfonylamino, N- (2-methylbenzenesulfonyl) -methylamino, N- (4-methylbenzenesulfonyl) -methylamino, N- (2-methoxybenzenesulfonyl) -methylamino- , N- (4-methoxybenzenesulfonyl) -methyl amino-, N- (2-fluorobenzenesulfonyl) -methylamino, N- (4-fluorobenzenesulfonyl) -methylamino, N- (2-chlorobenzenesulfonyl) -amino, N- (4-chlorobenzenesulfonyl) -methylamino, N- ( 2-bromobenzenesulfonyl) -methylamino, N- (4-bromobenzenesulfonyl) -methylamino, N- (2,4-dimethoxybenzenesulfonyl) -methylamino, N -benzylsulfonylmethylamino, N- (naphthalene- (1) -sulfonyl) -methylamino, N- (naphthalene- (2) -sulfonyl) -methylamino, N-benzoyl-cyclopentylamino, N-benzoylcyclohexylamino, N-benzoylcycloheptylamino, N-phenylacetyl-cyclopentylamino, N-phenylacetyl cyclohexylamino, N-phenylacetylcycloheptylamino, N-benzoylcyclopentylmethylamino, N-benzoylcyclohexylmethylamino, N-benzoylcycloheptylmethylamino, N-phenylacetylcyclopentylmethylamino, N-phenylacetylcyclohexylmethylamino, N-phenylacetyl cycloheptylmethylamino, N- (3-phenylpropionyl) methylamino, N- (3-phenylpropionyl) ethylamino, N- (3-phenylpropionyl) isopropylamino, N- (3-phenylpropionyl) isobutylamino, N -benzoyl - (2-cyclopentylethyl) -amine o-, N-benzoyl- (2-cyclohexylethyl) -amino, N-benzoyl- (2-cycloheptylethyl) -amino, N-phenylacetyl- (2-cyclopentylethyl) -amino, N-phenylacetyl- (2-cyclohexylethyl ) amino, N-phenylacetyl (2-cycloheptylethyl) amino, N-benzoyl (3-cyclopentylpropyl) amino, N-benzoyl (3-cyclohexylpropyl) amino, N-benzoyl (3 cycloheptylpropyl) amino, N-phenylacetyl (3-cyclopentylpropyl) amino, N-phenylacetyl (3-cyclohexylpropyl) amino, N-phenylacetyl (3-cycloheptylpropyl) amino, N-acetyl cyclopentylamino, N-acetylcyclohexylamino, N-acetylcycloheptylamino, N-acetylcyclopentylmethylamino, N-acetylcyclohexylmethylamino, N-acetylcycloheptylmethylamino, N-acetyl- (2-cyclopentylethyl) amino , N-acetyl- (2-cyclohexylethyl) -amino, N-acetyl- (2-cycloheptylethyl) -amino, N-acetyl- (3-cyclopentylpropyl) -amino, N-acetyl- (3-cyclohexylpropyl) - amino, N-acetyl (3-cycloheptylpropyl) amino, N-acetylbenzylamino, N-acetyl (2-phenylethyl) amino, N-acetyl (3-phenylpropyl) amino, N benzoyl-benzylamine o-, N-benzoyl- (2-phenylethyl) -amino, N-benzoyl- (3-phenylpropyl) amino, 2-carboxycyclohexylcarbonylamino, 2-aminocarbonylcyclohexylcarbonylamino, phthalimido, tetrahydrophthalimido, hexahydrophthalimido , cis-hexahydrophthalimido, trans-hexahydrophthalimido, pyrrolidino, methylpyrrolidino, ethylpyrrolidino, isopropylpyrrolidino, piperidino, methylpiperidino, ethylpiperidino, isopropylpiperidino, hexamethyleneimino, methylhexamethyleneimino, ethylhexamethyleneimino, isopropylhexamethyleneimino, 2- Carboxymethyl-pyrrolidino, 2-oxo-pyrrolidino, 2-oxo-piperidino, 2-oxo-hexamethyleneimino, aminocarbonylamino, methylaminocarbonylamino, dimethylaminocarbonylamino, N-methylaminocarbonyl-methylamino, N- (dimethylaminocarbonyl) -methylamino, , N-dimethylaminocarbonylethylamino, N-dimethylaminocarbonylisopropylamino, N- (dimethylaminocarbonyl) -n-pentylamino, N-methylaminocarbonylethylamino, N-methylaminocarbonyl-n-pentylamino, N-methylaminocarbonyl-n-hexylamino , NM ethylaminocarbonyl-n-octylamino, N-methylaminocarbonylcyclohexylamino, ethylaminocarbonylamino, N-ethylaminocarbonyl-methylamino, N-ethylaminocarbonyl-ethylamino, N-ethylaminocarbonyl-n-hexylamino, N-ethylaminocarbonyl-n-heptylamino, N Ethylaminocarbonylcyclohexylamino, diethylaminocarbonylamino, N- (diethylaminocarbonyl) -methylamino, N- (diethylaminocarbonyl) ethylamino, N- (diethylaminocarbonyl) -n-butylamino, N- (diethylaminocarbonyl) -n-hexylamino, N (Diethylaminocarbonyl) -n-octylamino, isopropylaminocarbonylamino, N -isospropylaminocarbonyl-methylamino, n-butylaminocarbonylamino, N- (n-butylaminocarbonyl) -methylamino, N- (n-butylaminocarbonyl) ethylamino, N- ( n-butylaminocarbonyl) -isopropylamino, N- (n-butylaminocarbonyl) -n-butylamino, N- (n-butylaminocarbonyl) -n-hexylamino, N- (n-butylaminocarbonyl) -cyclohexylamino, N- (di-) (n-butyl) -aminocarbonyl) -amino, N- (di (n-butyl) -aminocarbonyl) -methylamino, N- (di (n-butyl) -aminocarbonyl) -ethylamino, N- (di - (n-butyl) -Ami nocarbonyl) n-butylamino, N- (di (n-butyl) aminocarbonyl) n-hexylamino, N- (n -pentylaminocarbonyl) ethylamino, N- (n-hexylaminocarbonyl) ethylamino, n -Hexylaminocarbonylamino, n-heptylaminocarbonylamino, n-octylaminocarbonylamino, N- (n-hexylaminocarbonyl) -n-butylamino, N- (n-hexylaminocarbonyl) -n-pentylamino, N- (n-hexylaminocarbonyl) -n- hexylamino, N- (n-hexylaminocarbonyl) -cyclohexylamino, di- (n-hexyl) -aminocarbonylamino, N- (di (n-hexyl) -aminocarbonyl) -methylamino, N- ((n-hexyl) -methylaminocarbonyl) amino, cyclohexylaminocarbonylamino, N-cyclohexylaminocarbonylmethylamino, N-cyclohexylaminocarbonylethylamino, N-cyclohexylaminocarbonyl-n-butylamino, N-cyclohexylaminocarbonylisobutylamino, N -cyclohexylaminocarbonyln-pentylamino, N -Cyclohexylaminocarbonyl-n-hexylamino, N-cyclohexylaminocarbonylcyclohexylamino, N- (ethylcyclohexylaminocarbonyl) -methylamino, N- (propylcyclohexylaminocarbonyl) -methylamino, N- (n-butylcyclohexylaminocarbonyl) -methylamino, N- Be nzylaminocarbonylisobutylamino, 2-imidazolidinon-1-yl, 3-methyl-2-imidazolidinon-1-yl, 3-ethyl-2-imidazolidinon-1-yl, 3-n-propyl-2-imidazolidinone 1-yl, 3-isopropyl-2-imidazolidinon-1-yl, 3-n-butyl-2-imidazolidinon-1-yl, 3-isobutyl-2-imidazolidinon-1-yl, 3-n- Pentyl 2-imidazolidinon-1-yl, 3-n-hexyl-2-imidazolidinon-1-yl, 3-cyclopentyl-2-imidazolidinon-1-yl, 3-cyclohexyl-2-imidazolidinon-1-yl -, 3-Cycloheptyl-2-imidazolidinon-1-yl, 3-benzyl-2-imidazolidinon-1-yl, 3- (3-hydroxybenzyl) -2-imidazolidinon-1-yl, 3- (4- Hydroxybenzyl) -2-imidazolidinon-1-yl, 3- (3-methoxybenzyl) -2-imidazolidinon-1-yl, 3- (4-methoxybenzyl) -2-imidazolidinon-1-yl, 3- (3 , 4-dihydroxybenzyl) -2-imidazolidinon-1-yl, 3- (3,4-dimethoxybenzyl) -2-imidazolidinon-1-yl, 3-cyclopentylmethyl-2-imidazolidinon-1-yl, 3-cyclohexylmethyl -2-imidazolidinon-1-yl, 3-cycloheptylmethyl-2-imidazolidinon-1-yl, 3- (2-phenylethyl) -2-imidazolidinon-1-yl, 3- (2-cyclopentylethyl) -2- imidazolidinone-1-yl, 3- (2-cyclohexylet hyl) -2-imidazolidinon-1-yl, 3- (2-cycloheptylethyl) -2-imidazolidinon-1-yl, 3- (3-phenylpropyl) -2-imidazolidinon-1-yl, 3- (3 Cyclopentylpropyl) -2-imidazolidinone-1-yl, 3- (3-cyclohexylpropyl) -2-imidazolidinon-1-yl, 3- (3-cycloheptylpropyl) -2-imidazolidinon-1-yl, 3,4 , 5,6-Tetrahydro-2-pyrimidone-1-yl, 3-methyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-ethyl-3,4,5,6 tetrahydro-2-pyrimidon-1-yl, 3-n-propyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-isopropyl-3,4,5,6-tetrahydro 2-pyrimidon-1-yl, 3-n-butyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-isobutyl-3,4,5,6-tetrahydro-2 - pyrimidon-1-yl, 3-n-pentyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-n-hexyl-3,4,5,6-tetrahydro-2 -pyrimidon-1-yl, 3-cyclopentyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-cyclohexyl-3,4,5,6-tetrahydro-2-pyrimidone-1 -yl, 3-cycloheptyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-benzyl-3,4,5,6-tetrahydro-2-pyrimidone-1-yl, 3- (3-Hydroxybenzyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (4-hydroxybenzyl) -3,4,5,6-tetrahydro 2-pyrimidon-1-yl, 3- (3-methoxybenzyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (4-methoxybenzyl) -3,4,5, 6-tetrahydro-2-pyrimidon-1-yl, 3- (3,4-dihydroxybenzyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (3,4-dimethoxybenzyl ) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-cyclohexylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3-cycloheptylmethyl-3, 4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (2-phenylethyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (2-cyclopentylethyl ) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3- (2-cyclohexylethyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 3 (2-Cycloheptylethyl) -3,4,5,6-tetrahydro-2-pyrimidone-1-yl, 3- (3-phenylpropyl) -3,4,5,6-tetrahydro-2-pyrimidone-1-yl , 3- (3-Cyclopentylpropyl) -3,4,5,6-tetrahydro-2-pyrimidone-1-yl, 3- (3-cyclohexylpropyl) -3,4,5,6-tetrahydro-2-pyrimidone 1-yl, 3- (3-cycloheptylpropyl) -3,4,5,6-tetrahydro-2-pyrimidon-1-yl, 2-chloroethylaminocarbonylamino, 3-chloropropylaminocarbonylamino, 2-bromoethylaminocarbonylamino, 3-bromopropylaminocarbonylamino - (N-2-chloroethyl-methylaminocarbonyl) -amino, (N-2-bromoethyl-methylaminocarbonyl) -amino, (N-2-chloropropyl-methylaminocarbonyl) -amino, tert -butylcarbonylamino or (N-2-bromopropyl ethylaminocarbonyl) amino group,
for R₂ those of the hydrogen atom, the methyl, ethyl, n-propyl or isopropyl group,
for R₃ is the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, 1-methylpropyl, 1-methylbutyl , 2-methylbutyl, 3-methylbutyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylpropyl or 1,1-diethylethyl group,
R₄ represents the carboxy, cyano, 1H-tetrazolyl, 1-triphenylmethyl-tetrazolyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl or tert-butoxycarbonyl group and
for R₅ that of the hydrogen, fluorine, chlorine or bromine atom into consideration.

Preferred compounds of the above general formula I are those in which
R₁ is a hydrogen, chlorine or bromine atom, a methyl, hydroxy, methoxy, ethoxy, 2-carboxymethyl-pyrrolidino, pyrrolidino, piperidino, methylpiperidino, 2-pyrrolidinone, 2-piperidinone or 2 Aminocarbonylcyclohexylcarbonylamino group, an amino or methylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 4 carbon atoms, a cyclohexyl, cyclohexylmethyl, benzyl or dimethoxybenzyl group, an optionally substituted on the nitrogen atom by a cyclohexyl, cyclohexylmethyl, benzyl or dimethoxybenzyl group-substituted N-acylamino group in which the acyl part is an alkanoyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 2 to 4 carbon atoms in total, an alkylsulfonyl group having 1 to 4 carbon atoms, a cyclohexylcarbonyl or phenylalkanoyl group having 1 or 2 carbon atoms in the alkanoyl part, a Benzoyl, benzylsulfonyl, benzenesulfonyl or chlorophenylsulfonyl group, a Alkylsultam (1) group, an optionally fully or partially hydrogenated phthalimido group or a group of the formula

in which
R₆, R₇ and R₈, which may be the same or different, are hydrogen atoms, alkyl groups having 1 to 6 carbon atoms, cyclohexyl, cyclohexylmethyl, benzyl, hydroxybenzyl, dihydroxybenzyl, methoxybenzyl or dimethoxybenzyl groups or
R₇ is also a 3-chloro-n-propyl group or
R₆ and R₇ together represent an n-propylene group,
R₂ is a hydrogen atom or a methyl group,
R₃ represents an n-propyl or n-butyl group,
R₄ represents a carboxy, methoxycarbonyl, tert.butoxycarbonyl, 1H-tetrazolyl or 1-triphenylmethyl-tetrazolyl group and
R₅ represents a hydrogen, chlorine or bromine atom,
their 1, 3-isomer mixtures, their tautomers, their enantiomers and their addition salts with organic or inorganic acids or bases.

Particularly preferred compounds of the above general formula I are the imidazo-pyridines and purines, in which
R₁ is a hydrogen atom, an optionally substituted on the nitrogen atom by an alkyl group having 1 to 3 carbon atoms, by a cyclohexyl or benzyl substituted amino or N-acylamino group, in which the acyl radical is an alkanoyl group having 2 to 5 carbon atoms or a cyclohexylcarbonyl group, one optionally completely or partially hydrogenated phthalimido group or a group of the formula

in which
R₈ represents a methyl, benzyl, hydroxybenzyl, dihydroxybenzyl, methoxybenzyl or dimethoxybenzyl group and
R₆ and R₇ together represent an n-propylene group,
R₂ is a hydrogen atom or a methyl group,
R₃ represents an n-propyl or n-butyl group,
R₄ is a carboxy or 1H-tetrazol-5-yl group and
R₅ is a hydrogen atom,
their 1, 3-isomer mixtures, their tautomers, their enantiomers and their addition salts with organic or inorganic acids or bases.

According to the invention, the compounds are obtained according to the following Method:

• a) Cyclization of a compound of the general formula in the
  R₁, R₂ and A₁ to A₄ are as defined above,
  one of the radicals X₁ or Y₁ is a group of the general formula and the other of X₁ or Y₁ is a group of the general formula represent, wherein
  R₃ and R₅ are as defined above,
  R₉ represents a hydrogen atom or an R₃CO group, wherein R₃ is defined as mentioned above,
  Z₁ and Z₂, which may be the same or different, optionally substituted amino groups or optionally substituted by lower alkyl groups hydroxy or mercapto groups or
  Z₁ and Z₂ 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, but one of X₁ or Y₁ represents a group of the general formula must represent.
  The cyclization is conveniently carried out in a solvent or solvent mixture such as ethanol, isopropanol, glacial acetic acid, benzene, chlorobenzene, toluene, xylene, glycol, glycol monomethyl ether, diethylene glycol dimethyl ether, sulfolane, dimethylformamide, tetralin or in an excess of the acylating agent used to prepare the compound of general formula II , z. Example, in the corresponding nitrile, anhydride, acid halide, ester or amide, for example at temperatures between 0 and 250 ° C, but preferably at the boiling temperature of the reaction mixture, optionally in the presence of a condensing agent such as phosphorus oxychloride, thionyl chloride, sulfuryl chloride, sulfuric acid, p-toluenesulfonic acid , Methanesulfonic acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, acetic anhydride or, if appropriate, also in the presence of a base such as potassium ethylate or potassium tert-butylate. However, the cyclization can also be carried out without a solvent and / or condensing agent.
  However, the reaction is particularly advantageously carried out in such a way that a compound of general formula II in the reaction mixture by reduction of a corresponding o-nitro-amino compound is optionally prepared in the presence of a carboxylic acid of the general formula R₃COOH or by acylation of a corresponding o-diamino compound. Upon termination of the reduction of the nitro group on the Hydroxylaminstufe is obtained in the subsequent cyclization of the N-oxide of a compound of general formula I. The resulting N-oxide is then converted by reduction into a corresponding compound of general formula I.
  The subsequent reduction of the resulting N-oxide of the formula I is preferably carried out in a solvent such as water, water / ethanol, methanol, glacial acetic acid, ethyl acetate or dimethylformamide with hydrogen in the presence of a hydrogenation catalyst such as Raney nickel, platinum or palladium / carbon, with metals such Iron, tin or zinc in the presence of an acid such as acetic acid, hydrochloric acid or sulfuric acid, with salts such as iron (II) sulfate, stannous chloride or sodium dithionite, or with hydrazine in the presence of Raney nickel at room temperature.
• b) reaction of a compound of the general formula in the
  R₁ to R₃ and A₁ to A₄ are as defined above,
  with a biphenyl compound of the general formula in the
  R₄ and R₅ are as defined above and
  Z₃ is a nucleophilic leaving group such as a halogen atom, e.g. A chlorine, bromine or iodine atom, or a substituted sulphonyloxy group, e.g. A methanesulfonyloxy, phenylsulfonyloxy or p-toluenesulfonyloxy group.
  The reaction is conveniently carried out in a solvent or solvent mixture such as methylene chloride, diethyl ether, acetone, tetrahydrofuran, dioxane, dimethylsulfoxide or benzene optionally in the presence of an acid-binding agent such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium tert-butylate, sodium hydride, triethylamine or pyridine the two latter can be used simultaneously as a solvent, preferably at temperatures between 0 and 100 ° C, z. B. at temperatures between room temperature and 50 ° C, performed.
  In the reaction, a mixture of the 1- and 3-isomers is preferably obtained which, if desired, is subsequently separated into the corresponding 1- and 3-isomers, preferably by chromatography using a support such as silica gel or aluminum oxide.
• c) For the preparation of a compound of general formula I in which R₄ represents a carboxy group:
  Transfer of a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined above and
  R₄ 'represents a group convertible by hydrolysis, thermolysis or hydrogenolysis into a carboxy group.
  For example, functional derivatives of the carboxy group, such as their unsubstituted or substituted amides, esters, thiol esters, orthoesters, imino ethers, amidines or anhydrides, the nitrile group or the tetrazolyl group by hydrolysis into a carboxy group,
  Esters with tertiary alcohols, e.g. B. the tert-butyl ester, by means of thermolysis in a carboxy group and
  Esters with aralkanols, e.g. As the benzyl ester, are converted by hydrogenolysis in a carboxy group.
  The hydrolysis is conveniently carried out either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, trichloroacetic acid or trifluoroacetic acid 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, z. B. at temperatures between room temperature and the boiling temperature of the reaction mixture, carried out. In the hydrolysis in the presence of an organic acid such as trichloroacetic acid or trifluoroacetic acid optionally present alcoholic hydroxyl groups can be converted simultaneously into a corresponding acyloxy group as the trifluoroacetoxy.
  If R₄ 'in a compound of the general formula V is a cyano or aminocarbonyl group, these groups may also be reacted with a nitrite, eg. As sodium nitrite, in the presence of an acid such as sulfuric acid, this is suitably used simultaneously as a solvent, be converted at temperatures between 0 and 50 ° C in the carboxy group.
  If R₄ 'in a compound of general formula V, for example, the tert.Butyloxycarbonylgruppe, the tert.-butyl group may also be 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 p-toluenesulfonic acid, sulfuric acid, phosphoric acid or polyphosphoric acid preferably at the boiling temperature of the solvent used, for. B. at temperatures between 40 ° C and 100 ° C, are split off.
  If R₄ 'in a compound of general formula V, for example, the benzyloxycarbonyl group, the benzyl group may also be hydrogenolytically in the presence of a hydrogenation catalyst such as palladium / carbon in a suitable solvent such as methanol, ethanol, ethanol / water, glacial acetic acid, ethyl acetate, dioxane or dimethylformamide preferably at Temperatures between 0 and 50 ° C, z. B. at room temperature, and a hydrogen pressure of 1 to 5 bar are split off. In the hydrogenolysis other radicals, for. 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, mitreduziert or by hydrogen atoms, eg. For example, a halogen atom can be replaced by a hydrogen atom.
  If R₁ in a compound of the general formula V denotes one of the hydrolyzable radicals mentioned at the outset, then it can be converted into a corresponding amino compound during the reaction.
• d) For the preparation of a compound of the general formula I in which R₄ represents a 1H-tetrazolyl group:
  Cleavage of a protecting group from a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined above and
  R₄ "represents a 1H-protected 1H-tetrazolyl group in the 1-position.
  Examples of protective groups are the triphenylmethyl, trimethyltin, tributyltin, triphenyltin, propionitrile or p-nitrobenzyl groups.
  The cleavage of a protective moiety used is preferably carried out in the presence of a hydrogen halide, preferably in the presence of hydrogen chloride, in the presence of a base such as sodium hydroxide or alcoholic ammonia in a suitable solvent such as methylene chloride, methanol, methanol / ammonia, ethanol or isopropanol at temperatures between 0 and 100 ° C, but preferably at room temperature, or, if the reaction is carried out in the presence of alcoholic ammonia, at elevated temperatures, for. B. at temperatures between 100 and 150 ° C, preferably at temperatures between 120 and 140 ° C.
• e) For the preparation of a compound of general formula I in which R₄ represents a 1H-tetrazolyl group:
  Reaction of a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined above,
  with hydrazoic acid.
  The reaction is preferably carried out in a solvent such as benzene, toluene or dimethylformamide at temperatures between 80 and 130 ° C, preferably at 125 ° C. Here, the hydrazoic acid is particularly advantageous during the reaction of an alkali azide, z. From sodium azide, in the presence of a weak acid such as ammonium chloride.
• f) For the preparation of compounds of general formula I in which R₁ represents an optionally substituted by an alkyl group having 1 to 6 carbon atoms, substituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl amino group, wherein, unless otherwise stated, the The above-mentioned alkyl moieties may each contain 1 to 3 carbon atoms and the cycloalkyl moieties may each contain 5 to 7 carbon atoms.
  Transfer of a compound of the formula in the
  R₂ to R₅ and A₁ to A₄ are as defined above and
  R₁₀ represents a group convertible by hydrolysis, hydrogenolysis or transamidation into an optionally substituted by an alkyl group having 1 to 6 carbon atoms, substituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, wherein, unless otherwise stated, the above-mentioned alkyl moieties each 1 to 3 carbon atoms and the cycloalkyl parts may each contain 5 to 7 carbon atoms.
  For example, acylamino groups, e.g. B. the valeroylamino, benzoylamino or phthalimido group, by hydrolysis in an amino group and
  Imino groups, z. As the phthalimino group are converted by means of transamidation in an amino group.
  The hydrolysis is conveniently carried out either in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, trichloroacetic acid or trifluoroacetic acid 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, z. B. at temperatures between room temperature and the boiling temperature of the reaction mixture, carried out. In the hydrolysis in the presence of an organic acid such as trichloroacetic acid or trifluoroacetic acid optionally present alcoholic hydroxy groups can be converted simultaneously into a corresponding acyloxy group as the trifluoroacetoxy.
  If R₁₀ is a phthalimido group, this group may be in the presence of a primary organic base such as methylamine, ethylamine or propylamine or hydrazine optionally in a suitable solvent such as methanol, ethanol, isopropanol, dimethylformamide, methanol / dimethylformamide or methanol / water by transamidation at temperatures between 0 and 50 ° C, but preferably at room temperature, particularly advantageous converted into an amino group.
• g) For the preparation of compounds of the general formula I in which R₁ is a group of the formula represents:
  Reaction of a compound of the formula in the
  R₂ to R₅ and A₁ to A₄ are as defined above and
  R₁₁ represents a R₆NH group, wherein R₆ is as defined above, with a compound of formula in the
  R₇ and R₈ are as defined above,
  Z₄ a nucleophilic leaving group such as a chlorine or bromine atom or also
  Z₄ together with R₇ represent a nitrogen-carbon bond.
  The reaction is preferably carried out in a solvent such as tetrahydrofuran, dioxane, ethylene chloride or benzene optionally in the presence of an acid-binding agent such as triethylamine or pyridine at temperatures between 0 and 100 ° C, preferably at temperatures between 20 and 80 ° C.
• h) For the preparation of compounds of the general formula I in which R₁ is an N-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:
  Acylation of a compound of the general formula in the
  R₂ to R₅ and A₁ to A₄ are as defined above and
  R₁₂ is an amino group optionally substituted by an alkyl group having 1 to 6 carbon atoms, substituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, wherein, unless mentioned otherwise, the above-mentioned alkyl moieties each have 1 to 3 carbon atoms and the cycloalkyl moieties 5 respectively to 7 carbon atoms, with a compound of general formula R₁₃-W-OH (XII) in the
  W is a carbonyl or sulfonyl group,
  R₁₃ is an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a phenylalkyl, cycloalkyl or cycloalkylalkyl group each having 1 to 3 carbon atoms in the alkyl part and 5 to 7 carbon atoms in the cycloalkyl part, a phenyl, naphthyl, 2 Carboxycyclohexyl or 2-aminocarbonylcyclohexyl group, wherein the above-mentioned phenyl nucleus may be 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, or also when W represents a carbonyl group, a hydrogen atom, or with their reactive derivatives such as their acid halides, acid esters or acid anhydrides.
  Examples of suitable reactive derivatives of a compound of the formula XII are their esters, such as the methyl, ethyl or benzyl esters, their thioesters, such as the methylthio or ethylthioester, their halides, such as the acid chloride, their anhydrides or imidazolides.
  The reaction is conveniently 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 an acid activating or dehydrating agent such as thionyl 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, optionally in the presence of an inorganic or tertiary organic base, such as sodium hydroxide, potassium carbonate, triethylamine or pyridine, the two latter can also serve as a solvent, at temperatures between -25 and 100 ° C, but preferably at temperatures between -10 and 80 ° C, carried out.
• i) For the preparation of a compound of the formula I in which R₆ and R₇ together represent an ethylene or n-propylene group:
  Cyclization of a compound of the formula in the
  R₂ to R₅, R₈ and A₁ to A₄ are as defined above,
  Hal is a chlorine, bromine or iodine atom and
  n represent the number 2 or 3 and, if necessary, subsequent reaction with a compound of the formula R₈-Hal (XIV) in the
  R₈ with the exception of the hydrogen atom as defined above and
  Hal represents a chlorine, bromine or iodine atom.
  The cyclization and, if necessary, the subsequent alkylation is conveniently carried out in a solvent such as methanol, ethanol, benzene or dimethyl sulfoxide optionally in the presence of a phase transfer catalyst such as benzyltriethylammonium bromide in the presence of an acid-binding agent such as sodium hydroxide, sodium methylate, sodium ethylate, sodium hydride or potassium tert-butylate at temperatures between 20 and 100 ° C, preferably at temperatures between 30 and 70 ° C performed.

An isomer mixture of a compound obtained in accordance with the invention The general formula I may, if desired, preferably chromatographically using a carrier such as silica gel or alumina separated into their enantiomers become.

Furthermore, the obtained compounds of the general Formula I in their acid addition salts, in particular for the pharmaceutical application in its physiologically acceptable Salts with inorganic or organic acids, converted become. As acids come for example for this Hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, Fumaric acid, succinic acid, lactic acid, citric acid, Tartaric acid or maleic acid into consideration.

In addition, the new compounds thus obtained can be general formula I, if these contain a caboxy group, if desired, then into their addition salts with inorganic or organic bases, in particular for the pharmaceutical application in their physiologically acceptable  Addition salts, convert. As bases come here, for example Sodium hydroxide, potassium hydroxide, cyclohexylamine, Ethanolamine, diethanolamine and triethanolamine into consideration.

The compounds used as starting materials of the general Formulas II to XIV are partly known from the literature or This is obtained by literature methods.

For example, one obtains a compound of the general Formula II by alkylation of a corresponding o-amino-nitro compound and subsequent reduction of the nitro group.

A compound used as starting material of the general Formulas III, V, VI, VII, VIII, IX, XI or XIII are obtained by alkylation of a corresponding o-diamine or a corresponding o-amino-nitro compound and subsequent Reduction of the nitro group and subsequent cyclization an o-diamino compound thus obtained or by NH alkylation a corresponding 1H compound, the so obtained Mixture of isomers then by conventional methods, z. B. by chromatography, can be separated.

The new compounds of general formula I and their Physiologically compatible addition salts have valuable pharmacological properties. They represent in particular Angiotensin II antagonists.

For example, the compounds were

A = 4 '- [(2-n-butyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
B = 4 '- [(2-n-butyl-5-methyl-6-phthalimido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
C = 4 '- [(2-n-butyl-1 H -imidazo [4,5-c] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid,
D = 4 '- [(2-n-butyl-5-amino-3 H -imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
E = 4 '- [(2-benzylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid,
F = 4 '- [(2-n-butyl-5-methyl-6-propionylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
G = 4 '- [(2-n-butyl-5-cyclohexylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
H = 4 '- [(2-n-butyl-5-N-cyclohexylcarbonyl-ethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
I = 4 '- [(2-n-butyl-5-methyl-6-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
J = 4 '- [(2-n-butyl-5- [3-benzyl-3,4,5,6-tetrahydro-2 (1H)] pyrimidino-3H-imidazo [4,5-b] pyridine-3 -yl) methyl] biphenyl-2-carboxylic acid and
K = 4 '- [(2-n-Propyl-5- (2-methylpropionylamino) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazole-5 yl) biphenyl

examined for their biological effects as follows:

Rats (male, 180-220 g) are supplemented with hexobarbital sodium (150 mg / kg i.p.) anesthetized. After the onset of anesthesia If a tracheostomy tube is placed, the animals are despinalized and then immediately artificially ventilated with a breathing pump. The arterial blood pressure is via a cannula in the arteria Carotis registered by means of a Bell & Howell pressure transducer. Substances are transmitted through a cannula into the jugular vein applied.

Test substances are administered at three dosages (10, 20 and 30 mg / kg i.v.), with one substance dose per animal  Is tested. Three minutes after intravenous administration The test substance is angiotensin II in increasing dosage administered intravenously and so a cumulative dose-response relationship for angiotensin II in the presence of the test substances reached. The measuring parameter is the increase of the arterial Blood pressure.

These dose-response curves are calculated using standard curves for Angiotensin II compared without test substances. By means of a Computer program, the rightward shifts in the dose Effect curves of angiotensin II determined by test substances and corresponding pA₂ values for the test substances calculated.

The substances A to K show in the described test pA₂ values between 5.1 and 7.9.

Furthermore, in the application of the above Compounds up to a dose of 30 mg / kg i.v. no toxic Side effects, eg. B. no negative inotropic effect and no arrhythmia can be observed. The connections are therefore well tolerated.

Due to their pharmacological properties are suitable the new compounds and their physiologically acceptable Addition salts for the treatment of hypertension and heart failure, also for the treatment of ischemic peripheral circulatory disorders, myocardial ischemia (angina), to Prevention of heart failure progression after myocardial infarction, for the treatment of diabetic nephrophathy, Glaucoma, gastrointestinal diseases and bladder disease.

The necessary to achieve a corresponding effect Dosage is expediently with intravenous administration 20 to 100 mg, preferably 30 to 70 mg, and when given orally 50 to 200 mg, preferably 75 to 150 mg, each 1 to 3 times a day. For this purpose, the invention can be prepared  Compounds of general formula I, if appropriate in combination with other active substances, together with one or more inert customary carriers and / or Diluents, z. B. with corn starch, lactose, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, Citric acid, tartaric acid, water, water / Ethanol, water / glycerine, water / sorbitol, water / polyethylene glycol, Propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances like hard fat or fat their suitable mixtures, in usual galenic preparations like tablets, drag'es, capsules, powders, suspensions or suppositories.

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

example A 2-n-butyl-7-methyl-imidazo [4,5-b] pyridine

3.6 g (29 mmol) of 2,3-diamino-4-methylpyridine and 3 ml of valeric acid in 30 ml of phosphorus oxychloride for 2 hours cooked under reflux. The reaction mixture is in vacuo eingedmbft and the residue with 100 ml of ice water. By adding 20% sodium hydroxide solution, the mixture is neutralized and then extracted 2x with 100 ml of ethyl acetate. After drying over magnesium sulfate and evaporation of the Solvens you get an oil.

Yield: 4.8 g (87% of theory),
R _f value: 0.40 (silica gel, mobile phase: ethyl methyl ketone / xylene = 1: 1)

C₁₁H₁₅N₃ (189,26):
Calc .:
C, 69.81; H 7.99; N 22,20,
Found .:
C 69.60; H, 7.91; N 21.96.

The following compounds are obtained analogously:

2-n-Butyl-imidazo [4,5-c] pyridine,
Oil, R _f value: 0.31 (silica gel, eluent: methylene chloride / ethanol = 9: 1);

8-n-butyl-2-benzylamino-purine,
Oil, R _f value: 0.55 (silica gel, eluent: methylene chloride / ethanol = 9: 1);

8-n-butyl-2-n-butylamino-purine,
Melting point: 111-114 ° C;

8-n-butyl-2-cyclohexylamino-purine,
Oil, R _f value: 0.60 (silica gel, eluent: methylene chloride / ethanol = 9: 1);

8-n-butyl-2-ethoxy-purine,
Melting point: 181-182 ° C;

8-n-butyl-2-methoxy-purine,
Melting point: 166 ° C;

8-n-butyl-purine,
Melting point: 178-180 ° C;

2-n-butyl-5-bromo-imidazo [4,5-b] pyridine,
Melting point: 223-225 ° C.

example B 2-n-butyl-5-valeroylamino-imidazo [4,5-b] pyridine

Prepared from 2-n-Pentanoylamino-3-nitro-pyridine analog Example 1.

Yield: 83% of theory,
Melting point: 148-150 ° C.

The following compounds are obtained analogously:

2-n-Butyl-5-dimethylamino-imidazo [4,5-b] pyridine,
Melting point: 128-129 ° C;

2-n-butyl-5-methyl-6-amino-imidazo [4,5-b] pyridine,
Oil, R _f value: 0.23 (silica gel, eluent: ethyl acetate / ethanol / ammonia = 90: 10: 1).

example C 2-n-Butyl-5- (cis-hexahydrophthalimido) -imidazo [4,5-b] pyridine

Prepared by reaction of 2-n-butyl-5-amino-imidazo [4,5-b] pyridine analogously with cis-hexahydrophthalic anhydride Example 4.

Yield: 63% of theory,
Oil, R _f value: 0.50 (silica gel, eluent: methylene chloride / ethanol = 9: 1).

The following compound is obtained analogously:

2-n-butyl-5-methyl-6-phthalimido-imidazo [4,5-b] pyridine,
Oil, R _f value: 0.77 (silica gel, eluent: methylene chloride / ethanol = 19: 1).

Example 1 4 '- [(2-n-butyl-5-methylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] phenyl-bi-2-carboxylic acid tert-butyl ester

1.8 g (3.5 mmol) of 2- [N-4- (2-tert-butoxycarbonyl-phenyl) -benzyl- N-pentanoylamino] -3-nitro-6-methylamino-pyridine are used in 200 ml of ethanol dissolved, with 1.0 g of 10% palladium on activated charcoal and 2 hours at room temperature with 5 bar Hydrogen pressure hydrogenated. After completion of hydrogen uptake is filtered off from the catalyst and evaporated. Of the The residue is dissolved in 20 ml of glacial acetic acid and allowed to stand for 30 minutes heated in the steam bath. Subsequently, the reaction mixture evaporated, the residue dissolved in 100 ml of ethyl acetate and with saturated sodium bicarbonate solution and with saturated Washed sodium chloride solution. After drying over Magnesium sulfate, evaporation of the solvent and column chromatography on silica gel (particle size: 0.06-0.2 mm, eluent: Petroleum ether / ethyl acetate = 1: 1) to give a colorless Oil.

Yield: 1.4 g (86% of theory),
Oil, R _f value: 0.27 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1).

C₂₉H₃₄N₄O₂ (470.61):
Calc .:
C 74.01; H 7,28; N 11.91,
Found .:
C, 73.86; H 7,35; N 12,13.

The following compounds are obtained analogously:

4 '- [(2-n-butyl-5-cyclohexylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.45 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-butyl-5-n-butylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.43 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-butyl-5-ethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.36 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-butyl-5-cyclohexylmethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.48 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-propyl-5- (2-methylpropylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1-triphenylmethyl-tetrazol-5-yl) biphenyl,
Melting point: 132-135 ° C;
4 '- [(2-n-butyl-5- [2,4-dimethoxybenzyl] amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.40 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-butyl-5-benzylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.36 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [(2-n-butyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.65 (silica gel, eluent: ethyl acetate / ethanol / ammonia = 20: 20: 1);
4 '- [(2-n-butyl-1 H -imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.42 (silica gel, eluent: methylene chloride / ethanol = 17: 1);
4 '- [(2-n-butyl-5-methoxy-1 H -imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.44 (silica gel, eluent: ethyl methyl ketone / xylene = 1: 2);
4 '- [(2-n-butyl-5-methoxy-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.48 (silica gel, eluent: ethyl methyl ketone / xylene = 1: 2);
4 '- [[2-n-butyl-5- (4-methylpiperidino) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenylmethyl-tetrazole-5 yl) biphenyl,
Melting point: 147-149 ° C.

example 2 4 '- [(2-n-Butyl-5-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2-carboxylic acid tert-butyl ester (I) and 4 '- [(2-n-Butyl-5-valeroylamino-1H-imidazo [4,5-b] pyridin-3-yl) methyl] -2-carboxylic acid tert-butyl ester (II)

8.9 g (10.6 mmol) of 2-n-butyl-5-valeroylamino-3H-imidazo [4,5-b] pyridine are dissolved in 400 ml of acetone, with 7.3 g (53 mmol) potassium carbonate and with 5.5 g (15.9 mmol) 4'-bromomethyl- biphenyl-2-carboxylic acid tert.butylester added and heated with stirring for 6 hours to reflux. The reaction mixture is filtered and the filtrate evaporated to dryness. The residue is passed through a silica gel column (particle size: 0.063-0.2 mm), using as eluent Mixture of petroleum ether and ethyl acetate in the ratio 3: 1 is used. The uniform factions will be concentrated to dryness and triturated with diethyl ether. The so crystallized solids are washed with ether and dried.

I: Yield: 4.2 g (73% of theory),
Melting point: 102-104 ° C.

C₃₃H₃₉N₄O₃ (539.70):
Calc .:
C 73.20; H 7,46; N 10.36,
Found .:
C 73,18; H 7.72; N 10,19.

II: Yield: 1.1 g (20% of theory),
Melting point: 107-108 ° C.

C₃₃H₃₉N₄O₃ (539.70):
Calc .:
C 73.20; H 7,46; N 10.36,
Found .:
C 73,14; H 7,44; N 10.38.

The following compounds are obtained analogously:

4 '- [(2-n-propyl-5-butanoylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Melting point: 157-158 ° C;
4 '- [(2-n-propyl-5-butanoylamino-1H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
amorphous, R _f value: 0.38 (silica gel, eluent: ethyl acetate);
4 '- [(2-n-propyl-5-butanoylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-4-bromo-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.40 (silica gel, eluent: methylene chloride / ethanol = 19: 1);
4 '- [(2-n-butyl-5-dimethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.37 (alumina, eluent: ethyl acetate / petroleum ether = 1: 1);
4 '- [(2-n-butyl-5-bromo-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.55 (silica gel, eluent: methyl ethyl ketone / xylene = 1: 2);
4 '- [(2-n-butyl-5-bromo-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.20 (silica gel, eluent: methyl ethyl ketone / xylene = 1: 2);
4 '- [(2-n-butyl-5-methyl-6-phthalimido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.52 (silica gel, eluent: methyl ethyl ketone / xylene = 1: 4);
4 '- [(2-n-butyl-5-methyl-6-phthalimido-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.18 (silica gel, eluent: methyl ethyl ketone / xylene = 1: 1);
4 '- [[2-n-butyl-5- (cis-hexahydrophthalimido) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenylmethyl-tetrazol-5-yl ) biphenyl,
Oil, R _f value: 0.45 (silica gel, eluent: ethyl acetate);
4 '- [(2-n-butyl-3H-imidazo [4,5-c] pyridin-3-yl) -methyl [biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.45 (silica gel, eluent: methylene chloride / ethanol = 9: 1);
4 '- [(2-n-butyl-1H-imidazo [4,5-c] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.50 (silica gel, eluent: methylene chloride / ethanol = 9: 1);
4 '- [(2-Benzylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.45 (silica gel, eluent: ethyl acetate);
4 '- [(2-n-butylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid methyl ester,
Melting point: 125-126 ° C;
4 '- [(2-Cyclohexylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid methyl ester,
Oil, R _f value: 0.52 (silica gel, eluent: methylene chloride / ethanol = 95: 5);
4 '- [(2-ethoxy-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid methyl ester,
Oil, R _f value: 0.55 (silica gel, eluent: methylene chloride / ethanol = 95: 5);
4 '- [(2-methoxy-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid methyl ester,
Oil, R _f value: 0.50 (silica gel, eluent: methylene chloride / ethanol = 95: 5).

example 3 4 '- [(2-n-butyl-5-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl - 2-carboxylic acid tert-butyl ester

3.4 g (6.3 mmol) of 4 '- [(2-n-butyl-5-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester are dissolved in 75 ml of ethanol, with 35 ml of 2N sodium hydroxide solution mixed and heated with stirring for 8 hours at 80 ° C. The reaction mixture is evaporated, taken up in ethyl acetate and extracted with water. The aqueous phase is 2 × with about 100 ml of ethyl acetate reextracted. The organic ones Phases are combined, washed with saturated brine and dried over magnesium sulfate. After evaporation of the solvent, the residue is triturated with petroleum ether crystallized.

Yield: 2.1 g (73% of theory),
Melting point: 112-124 ° C.

C₂₈H₃₂N₄O₂ (456.59):
Calc .:
C, 73.66; H 7.07; N 12,21,
Found .:
C 73.72; H 7,20; N 12,12.

The following compound is obtained analogously:

4 '- [(2-n-propyl-5-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.50 (silica gel, eluent: ethyl acetate).

example 4 4 '- [[2-n-Butyl-5- (N-acetyl-cyclohexylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

0.3 g (0.62 mmol) of 4 '- [(2-n-butyl-5-cyclohexylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid in 3.0 g (38 mmol) of acetyl chloride and 2 hours under Reflux cooked. The reaction mixture is evaporated, the Residue mixed with water and with aqueous ammonia solution neutralized. After acidification with glacial acetic acid formed The precipitate is filtered off with suction, washed with water and dried.

Yield: 0.22 g (68% of theory),
Melting point: 121-123 ° C.

C₃₂H₃₆N₄O₃ (524,67):
Calc .:
C 73,26; H 6,92; N 10.68,
Found .:
C, 72.43; H 6,93; N 10.96.

The following compounds are obtained analogously:

4 '- [(2-n-propyl-5-benzylcarbonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.36 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [[2-n-butyl-5- (cis-hexahydrophthalimido) -butyl 3H-imidazo [4,5-b] pyridin-3-yl] -methyl] biphenyl-2-carboxylate,
Oil, R _f value: 0.66 (silica gel, eluent: ethyl acetate);
4 '- [[2-n-butyl-5- (N-acetyl-n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester .
Oil, R _f value: 0.21 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [[2-n-butyl-5- (N-ethoxycarbonyl-ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.45 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [[2-n-butyl-5- (N-cyclohexylcarbonyl-ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.34 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [[2-n-butyl-5-N - [(2-methylpropionyl) -n-butylamino] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2 -carboxylic acid tert-butyl ester,
Oil, R _f value: 0.48 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1);
4 '- [[2-n-butyl-5- (N-ethoxycarbonyl-n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester .
Oil, R _f value: 0.53 (silica gel, eluent: petroleum ether / ethyl acetate = 1: 1).

example 5 4 '- [[2-n-Butyl-5- (N-acetyl-cyclohexylmethylamino) -3H-imidazo [4,5-b] p yridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 4 from 4 '- [(2-n-butyl-5-cyclohexylmethylamino)  3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2- carboxylic acid and acetyl chloride.

Yield: 93% of theory,
Melting point: 180-185 ° C.

C₃₃H₃₈N₄O₃ (538.20):
Calc .:
C 73.58; H 7.11; N 10.40,
Found .:
C 73.56; H 7:37; N 10.46.

example 6 4 '- [(2-n-butyl-5-propionylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 4 from 4 '- [(2-n-butyl-5-amino-3H- imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid and Propionic anhydride.

Yield: 66% of theory,
Melting point: 278-281 ° C.

C₂₇H₂₈N₄O₃ (456.55):
Calc .:
C 71.03; H 6,18; N 12,27,
Found .:
C, 70.86; H 6,23; N 12.40.

example 7 4 '- [[2-n-Butyl-5- (2-methyl-propionylamino) -3H-imidazo [4,5-b] pyridin-3 - yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 4 from 4 '- [(2-n-butyl-5-amino-3H- imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid and Isobutyryl.

Yield: 49% of theory,
Melting point: 250 ° C.

C₂₈H₃₀N₄O₃ (430.58):
Calc .:
C, 71.47; H 6,43; N 11.91,
Found .:
C 71,26; H, 6.31; N 11,66.

example 8 4 '- [[2-n-Butyl-5- (N- (3-chlorpropylaminocarbonyl) -amino) -3H-imidazo [4, 5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid butyl ester

1.3 g (2.9 mmol) of 4 '- [(2-n-butyl-5-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester are dissolved in 10 ml of dimethylformamide, with 1.4 g (12 mmol) 3-chloropropyl isocyanate and 40 hours at room temperature touched. After addition of 200 ml of ice water extracted twice with 100 ml of ethyl acetate. After drying over Magnesium sulfate, the solvent is evaporated and the residue triturated with ether. The formed precipitate is sucked off and dried.

Yield: 1.5 g (90% of theory),
Melting point: 207-209 ° C.

C₃₂H₃₈ClN₅O₃ (646,17):
Calc .:
C 66.71; H, 6.65; N 12,16,
Found .:
C 66.71; H 6.72; N 12,47.

The following compounds are obtained analogously:

4 '- [[2-n-Propyl-5- (N- (3-chloropropylaminocarbonyl) -amino) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert .butylester,
Oil, R _f value: 0.20 (silica gel, eluent: ethyl acetate);
4 '- [[2-n-butyl-5- (N-cyclohexylaminocarbonyl-ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.30 (silica gel, eluent: ethyl acetate / petroleum ether = 1: 1);
4 '- [[2-n-butyl-5- (N-cyclohexylaminocarbonyl-n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] -methyl] -biphenyl-2-carboxylic acid tert-butyl ester .
Oil, R _f value: 0.55 (silica gel, eluent: ethyl acetate / petroleum ether = 1: 2).

example 9 4 '- [(2-n-butyl-5-cyclohexylaminocarbonylamino-3H-imidazo [4,5-b] pyrid in-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 8 from 4 '- [(2-n-butyl-5-amino-3H- imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid and Cyclohexyl.

Yield: 46% of theory,
Melting point: 287-291 ° C.

C₃₁H₃₅N₅O₃ (525,66):
Calc .:
C, 70.83; H 6.71; N 13,32,
Found .:
C 69.01; H, 6.66; N 13,18.

example 10 4 '- [[2-n-butyl-5- (3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4, -5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid tert-butyl ester

0.26 g (5.3 mmol) of sodium hydride are dissolved in 20 ml of tert-butanol solved. After 5 minutes at room temperature, 0.58 g (1.0 mmol) 4 '- [[2-n-butyl-5- (N- (3-chloropropylaminocarbonyl) -] amino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester added in portions. It is stirred 10 Hours at room temperature. By adding 2N hydrochloric acid the pH is brought to 5 and the tert-butanol in vacuo evaporated. The residue is washed with 100 ml of ethyl acetate  and water is stirred, the organic phase separated and the aqueous phase 2 × extracted with 50 ml of ethyl acetate. The combined organic phases are washed with saturated saline washed and dried over magnesium sulfate. After evaporation of the solvent, the residue with ether triturated, the precipitate formed sucked off and dried.

Yield: 0.4 g (74% of theory),
R _f value: 0.33 (silica gel, eluent: ethyl acetate / ethanol = 9: 1).

C₃₂H₃₇N₅O₃ (539.68):
Calc .: C, 71.22; H, 6.91; N 12,98,
Found .:
C 70.99; H 6,98; N 12,81.

The following compound is obtained analogously:

4 '- [[2-n-propyl-5- (3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl -2-carboxylic acid tert-butyl ester,
Melting point: 175 ° C.

example 11 4 '- [[2-n-Butyl-5- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-i midazo [4,5-b] pyridin-3 -yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester

0.4 g (0.74 mmol) of 4 '- [[2-n-butyl-5- (N- (3-chloropropylaminocarbonyl) -] amino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl Tert-butyl 2-carboxylic acid are dissolved in 20 ml of dimethylformamide and 0.04 g (0.85 mmol) of sodium hydride added. The mixture is stirred for 10 minutes at 60 ° C, are 0.5 ml (4.24 mmol) of benzyl bromide and stirred for 3 hours at room temperature. The reaction mixture is poured onto ice and extracted 2 × with 100 ml of ethyl acetate. The combined organic  Phases are washed with saturated brine and dried over magnesium sulfate. After evaporation of the solvent gives a colorless oil.

Yield: 0.35 g (75% of theory),
R _f value: 0.41 (silica gel, eluent: methylene chloride / ethyl acetate = 1: 1),
Mass spectrum: M⁺ = 629.

The following compound is obtained analogously:

4 '- [[2-n-butyl-5- (3-methyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridin-3-yl ] methyl] biphenyl-2-carboxylic acid tert-butyl ester,
Oil, R _f value: 0.41 (silica gel, eluent: ethyl acetate / ethanol = 9: 1).

example 12 4 '- [[2-n-Butyl-5- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-i midazo [4,5-b] pyridin-3 -yl] methyl] biphenyl-2-carboxylic acid

0.35 g (0.55 mmol) of 4 '- [[2-n-butyl-5- (3-benzyl-3,4,5,6-tetrahydro- 2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] tert-butyl biphenyl-2-carboxylate are dissolved in 10 ml of methylene chloride dissolved and treated with 5 ml of trifluoroacetic acid. It is stirred for 65 hours at room temperature. The solvent will evaporated, the residue taken up in ice water and with Acetic acid acidified. The precipitate formed becomes filtered off, washed with water and dried at 60 ° C.

Yield: 0.26 g (82% of theory),
Melting point: 168-170 ° C.

C₃₅H₃₅N₅O₃ (573.70):
Calc .:
C 73,28; H 6,15; N 12,21,
Found .:
C 73.37; H, 6.51; N 12,12.

example 13 4 '- [[2-n-Butyl-5- (3-methyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-i midazo [4,5-b] pyridin-3 -yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (3-methyl) 3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 64% of theory,
Melting point: 249-252 ° C.

C₂₉H₃₁N₅O₃ (497.60):
Calc .:
C 70.00; H 6,28; N 14.00,
Found .:
C, 69.85; H 6.40; N 13,89.

example 14 4 '- [[2-n-butyl-5- (3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4, -5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (3,4,5,6 tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 80% of theory,
Melting point: 300-302 ° C.

C₂₈H₂₉N₅O₃ (483.58):
Calc .:
C 68,27; H 6,14; N 14,22,
Found .:
C 68.47; H 6,11; N 14,28.

example 15 4 '- [[2-n-Propyl-5- (3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4, 5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-propyl-5- (3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and Trifluoroacetic acid.

Yield: 92% of theory,
Melting point: 265-268 ° C.

C₂₇H₂₇N₅O₃ (469.55):
Calc .:
C 69.07; H 5.80; N 14.92,
Found .:
C 68.87; H 5.78; N 15.00.

example 16 4 '- [(2-n-butyl-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.-

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-1H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 72% of theory,
Melting point: 180-182 ° C.

C₂₄H₃₃N₃O₂ (385.47):
Calc .:
C, 74.78; H 6.01; N 10.90,
Found .:
C, 74.62; H 5.95; N 10.74.

example 17 4 '- [(2-n-butyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.-

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 72% of theory,
Melting point: 205-207 ° C.

C₂₄H₂₃N₃O₂ (385.47):
Calc .:
C, 74.78; H 6.01; N 10.90,
Found .:
C 74.75; H 5.98; N 10.87.

example 18 4 '- [(2-n-butyl-1H-imidazo [4,5-c] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.-

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 97% of theory,
Melting point: 82-86 ° C (dec.).

C₂₄H₂₃N₃O₂ (385.47):
Calc .:
C, 74.78; H 6.01; N 10.90,
Found .:
C 74.56; H 5.88; N 11.07.

example 19 4 '- [(2-n-butyl-3H-imidazo [4,5-c] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.-

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-3H-imidazo [4,5-c] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 76% of theory,
Melting point: 83-88 ° C (dec.).

C₂₄H₂₃N₃O₂ (385.47):
Calc .:
C, 74.78; H 6.01; N 10.90,
Found .:
C 73.03; H 6,13; N 10.71.

example 20 4 '- [(2-n-butyl-5-cyclohexylmethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-cyclohexylmethylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 23.6% of theory,
Melting point: 202-205 ° C.

C₃₁H₃₆N₄O₂ (496,66):
Calc .:
C, 74.97; H 7,31; N 11,28,
Found .:
C, 74.82; H, 7.84; N 10.98.

example 21 4 '- [(2-n-butyl-5-ethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] bip henyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-ethylamino) 3-H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 76% of theory,
Melting point: 245-247 ° C.

C₂₆H₂₈N₄O₂ (428.54):
Calc .:
C, 72.87; H 6,59; N 13.09,
Found .:
C 72.72; H, 6.65; N 12,84.

example 22 4 '- [(2-n-butyl-5-n-butylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl]-b iphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-n-butylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 67% of theory,
Melting point: 217-219 ° C.

C₂₈H₃₂N₄O₂ (456.59):
Calc .:
C, 73.66; H 7.06; N 12,27,
Found .:
C 73.46; H 7.03; N 12,12.

example 23 4 '- [(2-n-butyl-5-cyclohexylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl-l] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-cyclohexylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 67% of theory,
Melting point: 221-224 ° C.

C₃₀H₃₄N₄O₂ (482.63):
Calc .:
C 73,29; H 7,18; N 11.40,
Found .:
C 73.51; H 6.95; N 11,25.

example 24 4 '- [(2-n-butyl-5-methylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] phenyl-bi-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 61% of theory,
Melting point: 274-277 ° C.

C₂₅H₂₆N₄O₂ (414.51):
Calc .:
C, 72.44; H 6,32; N 13.52,
Found .:
C 72,26; H 6,26; N 13,30.

example 25 4 '- [(2-n-butyl-5-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl - 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-amino- 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 35% of theory,
Melting point: 238-240 ° C.

C₂₄H₂₄N₄O₂ (400,48):
Calc .:
C, 71.98; H, 6.04; N 13.99,
Found .:
C 71.90; H 5.96; N 13,86.

example 26 4 '- [(2-n-butyl-5-dimethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-dimethylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 81% of theory,
Melting point: 213-215 ° C.

C₂₆H₂₈N₄O₂ (428.54):
Calc .:
C, 72.87; H 6,57; N 13.08,
Found .:
C, 72.82; H 6.73; N 12,90.

example 27 4 '- [(2-n-butyl-5-benzylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] phenyl-bi-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-benzylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 67% of theory,
Melting point: 224-225 ° C.

C₃₁H₃₀N₄O₂ (490,61):
Calc .:
C, 75.89; H 6,16; N 11.42,
Found .:
C 75.70; H 6,24; N 11.37.

example 28 4 '- [[2-n-butyl-5- (2,4-dimethoxy-benzylamino) -3H-imidazo [4,5-b] pyridin - 3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (2,4-dimethoxybenzylamino) -] 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 73% of theory,
Melting point: 223-226 ° C.

C₃₃H₃₄N₄O₄ (490.61):
Calc .:
C, 71.98; H 6,22; N 10:18,
Found .:
C 71.70; H 6.21; N 10,16.

Example 29 4 '- [[2-n-Butyl-5- (N-isobutyryl-n-butylamino) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-isobutyryl) n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 33% of theory,
Melting point: 186-189 ° C.

C₃₂H₃₈N₄O₃ (490.61):
Calc .:
C, 72.98; H 7,27; N 10.64,
Found .:
C 73.09; H 7.45; N 10.53.

Example 30 4 '- [[2-n-Butyl-5- (N-acetyl-n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-acetyl) n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 36% of theory,
Melting point: 173-175 ° C.

C₃₀H₃₄N₄O₃ (498.63):
Calc .:
C 72,26; H 6,87; N 11,24,
Found .:
C 72.39; H 7,00; N 11.07.

Example 31 4 '- [[2-n-Butyl-5- (N-cyclohexylcarbonyl-ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5- (N-cyclohexylcarbonyl) ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 95% of theory,
Melting point: 203-205 ° C.

C₃₃H₃₈N₄O₃ (538.70):
Calc .:
C 73.58; H 7.11; N 10.40,
Found .:
C, 73.66; H 7,19; N 10.35.

Example 32 4 '- [[2-n-Butyl-5- (N-acetyl-ethylamino) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-acetyl) ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 80% of theory,
Melting point: 89-93 ° C.

C₃₃H₃₈N₄O₃ (470.58):
Calc .:
C 70.99; H 6,47; N 11,79,
Found .:
C 70.79; H 6,47; N 11.52.

Example 33 4 '- [(2-n-butyl-5-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-valeroylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 56% of theory,
Melting point: 240-242 ° C.

C₃₃H₃₈N₄O₃ (484.60):
Calc .:
C, 71.88; H, 6.66; N 11.56,
Found .:
C, 71.61; H 6.72; N 11,47.

Example 34 4 '- [(2-n-propyl-5-butanoylamino-3H-imidazo [4,5-b] pyridine 3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-propyl-5-butanoylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 68% of theory,
Melting point: 254-255 ° C.

C₂₇H₂₈N₄O₃ (456.55):
Calc .:
C 71.03; H 6,18; N 12,27,
Found .:
C, 70.98; H 6,25; N 12.36.

Example 35 4 '- [(2-n-propyl-5-butanoylamino-3H-imidazo [4,5-b] pyridine 3-yl) methyl] biphenyl-4-bromo-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-propyl-5-butanoylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-4-bromo- 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 83% of theory,
Melting point: 244-245 ° C.

C₂₇H₂₇N₄O₃Br (535.54):
Calc .:
C 60.56; H 5.08; N, 10.46; Br 14.92,
Found .:
C 60.42; H 5.07; N, 10.41; Br 14.82.

Example 36 4 '- [[2-n-propyl-5- (2-methyl-valeroylamino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid 37755 00070 552 001000280000000200012000285913764400040 0002004025358 00004 37636

Prepared analogously to Example 12 from 4 '- [[2-n-propyl-5- (2-methyl- valeroylamino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 97% of theory,
Melting point: 244-245 ° C.

C₂₉H₃₂N₄O₃ (484.61):
Calc .:
C, 71.88; H, 6.66; N 11.56,
Found .:
C 71.77; H 6.79; N 11.51.

Example 37 4 '- [(2-n-propyl-5-benzylcarbonylamino-3H-imidazo [4,5-b] pyridine 3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-propyl-5-benzylcarbonylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 93% of theory,
Melting point: 252-254 ° C.

C₃₁H₂₈N₄O₃ (504.60):
Calc .:
C 73.79; H 5.59; N 11.10,
Found .:
C, 73.85; H 5.78; N 10.93.

Example 38 4 '- [(2-n-propyl-5-butanoylamino-1H-imidazo [4,5-b] pyridine 1-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-propyl-5-butanoylamino) 1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 88% of theory,
Melting point: 120 ° C.

C₂₇H₂₈N₄O₃ (456.55):
Calc .:
C, 70.34; H 6,23; N 12,15,
Found .:
C 70,14; H 6,24; N 12.34.

Example 39 4 '- [[2-n-Butyl-5- (N-ethoxycarbonyl-ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-ethoxycarbonyl- ethylamino-3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 95% of theory,
Melting point: 182-185 ° C.

C₂₉H₃₂N₄O₃ (500.61):
Calc .:
C 69.58; H, 6.44; N 11,19,
Found .:
C 69.72; H 6,57; N 11,13.

Example 40 4 '- [[2-n-Butyl-5- (N-cyclohexylaminocarbonyl-ethylamino) -3H- imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5- (N-cyclohexylaminocarbonyl) ethylamino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 95% of theory,
Melting point: 182-185 ° C.

C₃₃H₃₉N₅O₃ (500.61):
Calc .:
C 71.58; H 7,10; N 12.65,
Found .:
C 71.77; H 7,22; N 12.59.

Example 41 4 '- [[2-n-Butyl-5- (N-ethoxycarbonyl-n-butylamino) -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-ethoxycarbonyl- n-butylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 37% of theory,
Melting point: 154-156 ° C.

C₃₁H₃₆N₄O₄ (528,66):
Calc .:
C, 70.43; H 6,86; N 10.60,
Found .:
C, 70.68; H 7,10; N 10.50.

Example 42 4 '- [[2-n-Butyl-5- (N-cyclohexylaminocarbonyl-n-butylamino) -3 H imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (N-cyclohexylaminocarbonyl) n-butylamino) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 89% of theory,
Melting point: 195-198 ° C.

C₃₅H₄₃N₅O₃ (581.47):
Calc .:
C 72,26; H 7.45; N 12.04,
Found .:
C 72,29; H, 7.66; N 11,81.

Example 43 4 '- [[2-n-Butyl-5- (n-butylaminocarbonylamino) -1H-imidazo [4,5-b] pyridin-1-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (n-butylaminocarbonylamino) -] 1H-imidazo [4,5-b] pyridin-1-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 83% of theory,
Melting point: 290-295 ° C.

C₂₉H₃₃N₅O₃ (499.62):
Calc .:
C 69.72; H, 6.66; N 14.02,
Found .:
C, 69.62; H 6.76; N 13,98.

Example 44 4 '- [[2-n-Butyl-5- (cis-hexahydrophthalimido) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- (cis] hexahydrophthalimido) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 84% of theory,
Melting point: 113-115 ° C.

C₃₂H₃₂N₄O₄ (536.64):
Calc .:
C, 62.76; H 5,11; N 8.61,
Found .:
C, 62.79; H, 5.21; N 8,48.

Example 45 4 '- [(2-n-butyl-5-methoxy-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methoxy- 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 66% of theory,
Melting point: 224-225 ° C.

C₂₅H₂₅N₃O₃ (415.50):
Calc .:
C 72,27; H 6.06; N 10.11,
Found .:
C 72.09; H 6,14; N 9.91.

Example 46 4 '- [(2-n-butyl-5-methoxy-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid trifluoroacetate hydrate

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methoxy- 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 80% of theory,
Melting point: 126-128 ° C.

C₂₅H₂₅N₃O₃ × CF₃COOH × H₂O (547.54):
Calc .:
C 59.23; H 5.15; N 7.68,
Found .:
C 59.46; H 4.99; N 7.63.

Example 47 4 '- [(2-n-butyl-6-bromo-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-6-bromo-1H- imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 79% of theory,
Melting point: 239-240 ° C.

C₂₄H₂₂BrN₃O₂ (464.36):
Calc .:
C, 62.08; H 4.77; N 9.05; Br 17,21,
Found .:
C 61.83; H 4.71; N, 8, 92; 17.43.

Example 48 4 '- [(2-n-butyl-6-bromo-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-6-bromo-3H- imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 85% of theory,
Melting point: 221-223 ° C.

C₂₄H₂₂BrN₃O₂ (464.36):
Calc .:
C, 62.08; H 4.77; N 9.05; Br 17,21,
Found .:
C 61.95; H, 4.84; N 8,96; Br 17,38.

Example 49 4 '- [(2-n-butyl-7-methyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-7-methyl- 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 66% of theory,
Melting point: 239-240 ° C.

C₂₅H₂₅N₃O₂ (399.50):
Calc .:
C 75,16; H, 6.31; N 10.52,
Found .:
C, 74.92; H 6,29; N 10.63.

Example 50 4 '- [(2-n-butyl-5-methyl-6-phthalimido-3H-imidazo [4,5-b] pyridine 3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-phthalimido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 75% of theory,
Melting point: 336-340 ° C.

C₃₃H₂₈N₄O₄ (544.62):
Calc .:
C, 72.78; H 5:18; N 10.29,
Found .:
C 72.59; H 5:18; N 10.26.

Example 51 4 '- [(2-n-butyl-5-methyl-6-phthalimido-1H-imidazo [4,5-b] pyridine 1-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-phthalimido-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 63% of theory,
Melting point: 301-303 ° C.

C₃₃H₂₈N₄O₄ (544.62):
Calc .:
C, 72.78; H 5:18; N 10.29,
Found .:
C, 72.71; H 5.25; N 10,18.

Example 52 4 '- [(8-n-butyl-2-methoxy-9H-purin-9-yl) methyl] biphenyl-2- carboxylic acid

Prepared analogously to Example 12 from 4 '- [(8-n-butyl-2-methoxy- 9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 73% of theory,
Melting point: 146-148 ° C.

C₂₄H₂₄N₄O₄ (416.48):
Calc .:
C 69.21; H 5.81; N 13,45,
Found .:
C, 68.97; H 5.84; N 13,17.

Example 53 4 '- [(8-n-butyl-2-methoxy-7H-purin-7-yl) methyl] biphenyl-2- carboxylic acid

Prepared analogously to Example 12 from 4 '- [(8-n-butyl-2-methoxy- 7H-purin-7-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 73% of theory,
Melting point: 146-148 ° C.

C₂₄H₂₄N₄O₃ (416.48):
Calc .:
C 69.21; H 5.81; N 13,45,
Found .:
C 69.07; H 5.94; N 13,27.

Example 54 4 '- [(8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(8-n-butyl-9H-purine) 9-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 89% of theory,
Melting point: 81-83 ° C.

C₂₃H₂₂N₄O₂ (404.47):
Calc .:
C 68.30; H 5.98; N 13.85,
Found .:
C 68.72; H 5.77; N 13,46.

Example 55 4 '- [(8-n-butyl-7H-purin-7-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(8-n-butyl-7H-purine)  7-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 89% of theory,
Melting point: 81-83 ° C.

C₂₃H₂₂N₄O₂ (404.47):
Calc .:
C 68.30; H 5.98; N 13.85,
Found .:
C 68.42; H 5.97; N 13.66.

Example 56 4 '- [(2-benzylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-benzylamino-8-n- butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 13% of theory,
Melting point: 232-234 ° C.

C₃₀H₂₉N₅O₂ (491.60):
Calc .:
C 73.20; H 5.95; N 14,25,
Found .:
C 73,16; H 6.05; N 14,44.

Example 57 4 '- [(2-n-butyl-5-methyl-6-acetylamino-3H-imidazo [4,5-b] pyridin-3-yl) -methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-acetylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₂₈H₂₈N₄O₃.  

Example 58 4 '- [(2-n-butyl-5-methyl-6-amino-3H-imidazo [4,5-b] pyridine 3-yl) -methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₂₆H₂₆N₄O₂.

Example 59 4 '- [(2-n-butyl-5-methyl-6-propionylamino-3H-imidazo [4,5-b] pyridin-3-yl) -methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-propionylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₂₉H₃₂N₄O₃.

Example 60 4 '- [(2-n-butyl-5-methyl-6-butyrylamino-3H-imidazo [4,5-b] pyridin-3-yl) -methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-butyrylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₃₀H₃₄N₄O₃.  

Example 61 4 '- [(2-n-butyl-5-methyl-6-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₃₁H₃₆N₄O₃.

Example 62 4 '- [[2-n-butyl-5-methyl-6- (2-methyl-propylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5-methyl] 6- (2-methyl-propylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₂₉H₃₂N₄O₃.

Example 63 4 '- [(2-n-butyl-5-methyl-6-cyclohexylcarbonylamino-3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-cyclohexylcarbonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₃₂H₃₅N₄O₃.  

Example 64 4 '- [[2-n-butyl-5-methyl-6- (cis-hexahydrophthalimido) -3 H imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5-methyl] 6- (cis-hexahydrophthalimido) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 81% of theory,
Melting point: 261-263 ° C.

C₃₃H₃₄N₄O₄ (550.67):
Calc .:
C, 71.98; H 6,22; N 10:18,
Found .:
C 71.78; H 6,25; N 9.95.

Example 65 4 '- [[2-n-butyl-5-methyl-6- (3,4,5,6-tetrahydro-2 (1H) pyrimidinio) - 3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5-methyl] 6- (3,4,5,6-tetrahydro-2 (1H) pyrimidinio) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and Trifluoroacetic acid.

C₂₉H₃₁N₅O₃.  

Example 66 4 '- [[2-n-butyl-5-methyl-6- (3-methyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2- carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5-methyl] 6- (3-methyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] py-ridin-3-yl] methyl] biphenyl-2- carboxylic acid tert.-butyl ester and trifluoroacetic acid.

C₃₀H₃₃N₅O₃.

Example 67 4 '- [[2-n-Butyl-5- [3- (4-methoxy) benzyl-3,4,5,6-tetrahydro- 2 (1H) pyrimidinone] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- [3- (4- methoxy) benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert. butyl ester and trifluoroacetic acid.

C₃₅H₃₇N₅O₄.

Example 68 4 '- [[2-n-Butyl-5- [3- (4-hydroxy) benzyl-3,4,5,6-tetrahydro- 2 (1H) pyrimidinone] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- [3- (4- hydroxy) benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone] -3H-imidazo  [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert. butyl ester and trifluoroacetic acid.

C₃₄H₃₅N₅O₄.

Example 69 4 '- [[2-n-Butyl-5- [3-cyclohexylmethyl-3,4,5,6-tetrahydro- 2 (1H) pyrimidinone] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5- [3-cyclohexylmethyl] 3,4,5,6-tetrahydro-2 (1H) pyrimidinone] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert. butyl ester and trifluoroacetic acid.

C₃₄H₄₁N₅O₃.

Example 70 4 '- [[2-n-propyl-5 - [(2-carboxymethyl) pyrrolidino] -3 H -imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [[2-n-propyl-5 - [(2- carboxymethyl) pyrrolidino] -3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 37% of theory,
Melting point: 137-139 ° C.

C₂₉H₃₀N₄O₄ (498.62):
Calc .:
C, 69.86; H 6.06; N 11,24,
Found .:
C 69.59; H 6,20; N 11.04.

Example 71 4 '- [(2-n-butyl-6-phthalimido-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid trifluoroacetate

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-6-phthalimido- 1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 74% of theory,
Melting point: 168-170 ° C.

C₃₂H₂₆N₄O₄ × CF₃COOH (644.61):
Calc .:
C 63.35; H 4,22; N 8,96,
Found .:
C 63.50; H 4.53; N 9.06.

Example 72 4 '- [[8-n-butyl-2 (n-butylamino) -9H-purin-9-yl] methyl] biphenyl 2-carboxylic acid

0.45 g (0.95 mmol) of 4 '- [[8-n-butyl-2 (n-butylamino) -9H-purine] 9-yl] methyl] biphenyl-2-carboxylic acid methyl ester are dissolved in 20 ml Dissolved methanol and 10 ml of water, with 0.4 g of powdered potassium hydroxide and heated to reflux for 3 hours. Subsequently, the reaction mixture is evaporated and the Residue dissolved in 30 ml of water. It is filtered through carbon and acidified with glacial acetic acid. The precipitate formed becomes filtered off with suction, washed with water and dried.

Yield: 0.4 g (92% of theory),
Melting point: 213-215 ° C.

C₂₇H₃₁N₅O₂ (457.58):
Calc .:
C, 70.87; H 6,83; N 15.31,
Found .:
C 70.70; H 6,89; N 15,19.

Example 73 4 '- [(8-n-butyl-2-cyclohexylamino-9H-purin-9-yl) methyl] biphenyl 2-carboxylic acid

Prepared analogously to Example 72 from 4 '- [(8-n-butyl-2-cyclohexylamino) 9H-purin-9-yl) methyl] biphenyl-2-carbonsäuremethylester and methanolic potassium hydroxide.

Yield: 55% of theory,
Melting point: 213-215 ° C.

C₂₉H₃₃N₅O₂ (483.62):
Calc .:
C 72.02; H 6,88; N 14,48,
Found .:
C, 71.84; H 6,98; N 14.62.

Example 74 4 '- [(8-n-butyl-2-ethoxy-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 72 from 4 '- [(8-n-butyl-2-ethoxy- 9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid methyl ester and methanolic potassium hydroxide solution.

Yield: 48% of theory,
Melting point: 190-192 ° C.

C₂₅H₂₆N₄O₃ (430.51):
Calc .:
C 69.75; H 6.09; N 13.01,
Found .:
C 69.75; H 6,13; N 12,83.

Example 75 4 '- [(8-n-butyl-2-ethoxy-7H-purin-7-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 72 from 4 '- [(8-n-butyl-2-ethoxy- 7H-purin-7-yl) methyl] biphenyl-2-carboxylic acid methyl ester and methanolic potassium hydroxide solution.

Yield: 10% of theory,
Melting point: 155-158 ° C.

C₂₅H₂₆N₄O₃ (430.51):
Calc .:
C 69.75; H 6.09; N 13.01,
Found .:
C 69.95; H 6,10; N 11,83.

Example 76 4 '- [[2-n-propyl-5- (2-methyl-propyl) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

0.32 g (0.42 mmol) of 4 '- [(2-n-propyl-5- (2-methylpropylamino) -] 3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1triphenylmethyl- tetrazol-5-yl) biphenyl are dissolved in 20 ml of methanolic hydrochloric acid dissolved and stirred for 2 hours at room temperature. The Solvent is evaporated, the residue with 20 ml of water triturated, filtered off with suction and dried. After column chromatography on silica gel (particle size: 0.06-0.2 mm, eluent: Methylene chloride / ethanol 0-10%) gives a white solid.

Yield: 0.1 g (51% of theory),
Melting point: 128-130 ° C.

C₂₇H₃₀N₈ (466,60):
Calc .:
C 69.50; H, 6.48; N 24.02,
Found .:
C 69.44; H 6.73; N 24.04.

Example 77 4 '- [[2-n-Butyl-5- (2-aminocarbonyl-cyclohexylcarbonylamino) - 3H-imidazo [4,5-b] pyridin-3-yl] methyl] biphenyl-2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-butyl-5- (2-aminocarbonyl-) cyclohexylcarbonylamino) -3H-imidazo [4,5-b] pyridine 3-yl) methyl] -2- (1-triphenylmethyltetrazol-5-yl) biphenyl and methanolic hydrochloric acid.

Yield: 37% of theory,
Melting point: 165-175 ° C.

C₃₂H₃₅N₉O₂ (577.70):
Calc .:
C 66.53; H 6,11; N 21.82,
Found .:
C 65.73; H 6,13; N 21,84.

Example 78 4 '- [[2-n-Butyl-5- (cis-hexahydrophthalimido) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-butyl-5- (cis] hexahydrophthalimido) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] - 2- (1-triphenylmethyltetrazol-5-yl) biphenyl and glacial acetic acid.

Yield: 30% of theory,
Melting point: 127 ° C,
C₃₂H₃₂N₈O₂ (577.70),
Mass spectrum: M⁺ = 560.

Example 79 4 '- [[2-n-Butyl-5- (4-methyl-piperidino) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-butyl-5- (4-methyl) piperidino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-triphenylmethyl-tetrazol-5-yl) biphenyl and methanolic Hydrochloric acid.

Yield: 39% of theory,
Melting point: 187-189 ° C,
C₃₀H₃₄N₈ (506.70),
Mass spectrum: M⁺ = 605.

Example 80 4 '- [[2-n-propyl-5- [N- (3-phenylpropionyl) isobutylamino) -3 H imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-propyl-5- [N-] (3-phenylpropionyl) -isobutyl-amino) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1-triphenylmethyl-tetrazol-5-yl) -biphenyl and methanolic hydrochloric acid.

C₃₆H₃₈N₈O.

Example 81 4 '- [[2-n-propyl-5- (N-benzylaminocarbonyl-isobutylamino) -3 H imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-propyl-5- (N-benzylaminocarbonyl-  isobutylamino) -3H-imidazo [4,5-b] pyridin-3-yl] methyl] - 2- (1-triphenylmethyl-tetrazol-5-yl) -biphenyl and methanolic Hydrochloric acid.

C₃₅H₃₇N₉O.

Example 82 4 '- [[2-n-propyl-5- (N-cyclohexylaminocarbonyl-isobutylamino) - 3H-imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-propyl-5- (N-) cyclohexylaminocarbonyl-isobutylamino) -3-imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1-triphenylmethyl-tetrazol-5-yl) biphenyl and methanolic hydrochloric acid.

Yield: 47% of theory,
Melting point: sintering from 75 ° C.

C₃₄H₄₁N₉O (591.77):
Calc .:
C 69.01; H 6,98; N 21,30,
Found .:
C 68.86; H 6,88; N 21,18.

Example 83 4 '- [[2-n-Butyl-5- (3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone) - 3H-imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1H-tetrazol-5- yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-butyl-5- (3-benzyl- 3,4,5,6-tetrahydro-2 (1H) pyrimidinone) -3H-imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1-triphenylmethyl-tetrazol-5-yl) biphenyl and methanolic hydrochloric acid.

C₃₄H₃₅N₉O.  

Example 84 4 '- [(2-n-butyl-5-hydroxy-imidazo [4,5-b] pyridin-3-yl) methyl] - 2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-butyl-5-hydroxy- imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1-triphenylmethyl-tetrazol- 5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₃H₂₃N₇O.

Example 85 4 '- [(2-n-propyl-5-hydroxy-imidazo [4,5-b] pyridin-3-yl) methyl] - 2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-propyl-5-hydroxy- imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1-triphenylmethyl-tetrazol- 5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₂H₂₁N₇O.

Example 86 4 '- [[2-n-Butyl-5- (2-oxo-pyrrolidino) -imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-butyl-5- (2-oxo) pyrrolidino) -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenyl- methyl-tetrazol-5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₈H₂₈N₈O.  

Example 87 4 '- [[2-n-propyl-5- (2-oxo-pyrrolidino) -imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 75 from 4 '- [[2-n-propyl-5- (2-oxo) pyrrolidino) -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenyl- methyl-tetrazol-5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₇H₂₆N₈O.

Example 88 4 '- [[2-n-Butyl-5- (2-oxo-piperidino) -imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-butyl-5- (2-oxo) piperidino) -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenylmethyl-- tetrazol-5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₉H₃₀N₈O.

Example 89 4 '- [[2-n-propyl-5- (2-oxo-piperidino) -imidazo [4,5-b] pyridine 3-yl] methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [[2-n-propyl-5- (2-oxo) piperidino) -imidazo [4,5-b] pyridin-3-yl] methyl] -2- (1-triphenyl- methyl-tetrazol-5-yl) -biphenyl and methanolic hydrochloric acid.

C₂₈H₂₈N₈O.  

Example 90 4 '- [[2-n-butyl-5-methyl-6- (cis-hexahydrophthalimido) -1H-imidazo [4,5-b] pyridin-1-yl] methyl] biphenyl-2-carboxylic acid trifluoroacetate

Prepared analogously to Example 12 from 4 '- [[2-n-butyl-5-methyl] 6- (cis-hexahydrophthalimido) -1H-imidazo [4,5-b] pyridin-1-yl] methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 79% of theory,
Melting point: 188-190 ° C.

C₃₃H₃₄N₄O₄ × CF₃COOH (664.68):
Calc .:
C 63,24; H 5.31; N 8,42,
Found .:
C 63.52; H 5.65; N 8,69.

Example 91 4 '- [(2-n-butyl-5-methyl-6-dimethylaminocarbonylamido-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid trifluoroacetate

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 6-dimethylaminocarbonylamido-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 83% of theory,
Melting point: 147-149 ° C.

C₂₈H₃₁N₅O₃ × CF₃COOH (599.61):
Calc .:
C 60.09; H 5.37; N 11.68,
Found .:
C, 60.31; H 5.39; N 11.51.

Example 92 4 '- [(2-n-butyl-5-methyl-1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-methyl) 1H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 77% of theory,
Melting point: 230-232 ° C.

C₂₅H₂₅N₃O₂ (399.50):
Calc .:
C 75,16; H, 6.31; N 10.52,
Found .:
C 74,386; H 6,39; N 10.46.

Example 93 4 '- [(2-n-butyl-5-phthalimido-3H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-phthalimido- 3H-imidazo [4,5-b] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid tert.butyl ester and trifluoroacetic acid.

Yield: 78% of theory,
Melting point: 271-272 ° C.

C₃₂H₂₆N₄O₄ (530.59):
Calc .:
C, 72.44; H 4,94; N 10.56,
Found .:
C 72.37; H 4.99; N 10.48.

Example 94 4 '- [(2-n-Butyl-5- (4-chlorophenyl) sulfonylamido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid hydrate

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5- (4-chlorophenyl) sulfonylamido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

Yield: 63% of theory,
Melting point: 158-160 ° C.

C₃₀H₂₇N₄O₄ClS × H₂O (593.10):
Calc .:
C 60.75; H 4.93; N 9.45,
Found .:
C, 60.62; H 4.76; N 9,27.

Example 95 4 '- [(2-n-butyl-5-n-butylsulfonylamido-3H-imidazo [4,5-b] pyridine 3-yl) methyl] biphenyl-2-carboxylic acid

Prepared analogously to Example 12 from 4 '- [(2-n-butyl-5-n-butylsulfonylamido] 3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl 2-carboxylic acid tert-butyl ester and trifluoroacetic acid.

C₂₈H₃₂N₄O₄S (520,65).

The following compounds are obtained analogously:

4 '- [(2-n-butyl-5-n-propylsulfonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-isopropylsulfonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5- (3-chloropropylsulfonylamino) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-n-hexylsulfonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-benzylsulfonylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid.

Example 96 4 '- [(2-n-Butyl-5- (n-butansultam-1-yl) -3H-imidazo [4,5-b] pyridine 3-yl) methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-butyl-5- (n-butanesultam) 1-yl) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1-triphenylmethyl- tetrazol-5-yl) biphenyl and methanolic hydrochloric acid.

C₂₈H₃₀N₈O₂S (542,66).

The following compounds are obtained analogously:

4 '- [(2-n-Butyl-5- (n-butanesultam-1-yl) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazole-5 yl) biphenyl,
4 '- [(2-n-butyl-5- (n-propanesultam-1-yl) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazole-5 yl) biphenyl,
4 '- [(2-n-propyl-5- (n-propanesultam-1-yl) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazole-5 yl) biphenyl,
4 '- [(2-n-butyl-5- (n-butanesultam-1-yl) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-propyl-5- (n-butanesultam-1-yl) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5- (n-propanesultam-1-yl) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-Propyl-5- (n-propanesultam-1-yl) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid.

Example 97 4 '- [(2-n-butyl-5-methoxy-3H-imidazo [4,5-b] pyridin-3-yl) methyl] - 2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-butyl-5-methoxy- 3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1-triphenylmethyl- tetrazol-5-yl) biphenyl and methanolic hydrochloric acid.

Yield: 43% of theory,
Melting point: 206-207 ° C.

C₂₅H₂₅N₇O (439.52):
Calc .:
C 68.32; H 5.73; N 22.31,
Found .:
C 68.11; H 5.88; N 22,19.

Example 98 4 '- [(2-n-Butyl-imidazo [4,5-b] pyridin-5-on-3-yl) methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-butylimidazo [4,5-b] pyridin-5-on-3-yl) methyl] -2- (1-triphenylmethyl-tetrazol- 5-yl) biphenyl and methanolic hydrochloric acid.

Yield: 18% of theory,
Melting point: amorphous.

C₂₄H₂₃N₇O (425.50):
Calc .:
C 67.75; H 5.45; N 23.04,
Found .:
C 67.54; H 5.42; N 22,91.

Example 99 4 '- [(2-n-propyl-5- (2,2-dimethylpropionylamino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-propyl-5- (2,2-dimethylpropionylamino) -] 3H-imidazo [4,5-b] pyridin-3-yl) methyl] - 2- (1-triphenylmethyl-tetrazol-5-yl) biphenyl and methanolic Hydrochloric acid.

Yield: 81% of theory,
Melting point: 217-220 ° C.

C₂₈H₃₀N₈O (494.60):
Calc .:
C 67.99; H 6,11; N 22,66,
Found .:
C, 67.82; H 6,22; N 22.46.

Example 100 4 '- [(2-n-propyl-5-cyclohexylcarbonylamino) -3H-imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazol-5-yl) biphenyl

Prepared analogously to Example 76 from 4 '- [(2-n-propyl-5-cyclohexylcarbonylamino) 3H-imidazo [4,5-b] pyridin-3-yl) methyl] - 2- (1-triphenylmethyl-tetrazol-5-yl) biphenyl and methanolic Hydrochloric acid.

Yield: 89% of theory,
Melting point: 229-231 ° C.

C₃₀H₃₂N₈O (520,64):
Calc .:
C 69.21; H 6,20; N 21.52,
Found .:
C 69,14; H 6,20; N 21.32.

In the following pharmaceutical application examples can as active substance any suitable compound of the formula I. are used, in particular the compounds A to K of pharmacological test report:

Example I

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

manufacturing

In a part of the water the buffer substances and the Isotonans solved. The active ingredient is added and after completely filled with water to the nominal volume.

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

In a part of the water is dissolved methylglucamine and the Active ingredient with stirring and heating brought into solution. To Add the solvent with water to the nominal volume refilled.

Example III

Tablets containing 50 mg of active ingredient Active ingredient | 50.0 mg calcium phosphate 70.0 mg lactose 40.0 mg corn starch 35.0 mg polyvinylpyrrolidone 3.5 mg magnesium stearate 1.5 mg @ 200.0 mg

manufacturing

The active ingredient, CaHPO₄, lactose and corn starch evenly moistened with an aqueous PVP solution. The Mass is passed through a 2 mm sieve in a convection oven dried at 50 ° C and sieved again.

After admixing the lubricant, the granules on a Tabletting machine pressed.  

Example IV

Dragees containing 50 mg of active ingredient Active ingredient | 50.0 mg lysine 25.0 mg lactose 60.0 mg corn starch 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 an aqueous gelatin solution moistened. After screening and Drying, the granules are mixed with magnesium stearate and pressed into cores.

The cores thus produced are prepared by known methods covered with a shell. 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 lactose 86.0 mg corn starch 50.0 mg polyvinylpyrrolidone 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 an aqueous PVP solution moistened. The wet mass will passed through a 1.5 mm sieve and dried at 45 ° C. To The drying is again sieved and the magnesium stearate admixed. This mixture is pressed into cores.

The cores thus produced are prepared by known methods covered with a shell. The coating suspension or solution Dyes can be added.

Example VI

Capsules containing 250 mg of active ingredient Active ingredient | 250.0 mg corn starch 68.5 mg magnesium stearate  1.5 mg 320.0 mg

manufacturing

Active ingredient and cornstarch are mixed and mixed with water moistened. The moist mass is sieved and dried. The dry granules are sieved and treated with magnesium stearate mixed. The final mixture is sized into hard gelatin capsules 1 bottled.  

Example VII

Oral suspension containing 50 mg of active ingredient per 5 ml Active ingredient | 50.0 mg hydroxyethyl 50.0 mg sorbic acid 5.0 mg Sorbitol 70% 600.0 mg glycerin 200.0 mg Arome 15.0 mg Water, ad 5.0 ml

manufacturing

Distilled water is heated to 70 ° C. This is where dissolved with stirring hydroxyethyl cellulose. By adding Sorbitol solution and glycerin are cooled to room temperature. At room temperature, sorbic acid, flavor and active ingredient added. To vent the suspension is stirred evacuated. One 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 slightly pre-cooled suppository forms poured out.

Claims (10)

1. Heterocyclic imidazoles of the general formula in the
one or two of the radicals A₁, A₂, A₃ or A₄ is a nitrogen atom and the remaining radicals A₁, A₂, A₃ or A₄ each have a methine group,
R₁ is a hydrogen, fluorine, chlorine or bromine atom, a hydroxy, alkyl or alkoxy group, optionally substituted on the nitrogen atom by an alkyl group of 1 to 6 carbon atoms, mono- or disubstituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group Amino group wherein the substituents may be the same or different, or mono-substituted N-acylamino group in which the acyl group is an alkanoyl group having 1 to 7 carbon atoms, an alkoxycarbonyl group having 2 to 4 carbon atoms in total, an alkylsulfonyl group having 1 to 6 carbon atoms, a benzoyl Represents -, benzenesulfonyl, phenylalkanesulfonyl, naphthalenesulfonyl, 2-carboxy-cyclohexylcarbonyl, 2-aminocarbonyl-cyclohexylcarbonyl, cycloalkylcarbonyl, phenylalkanoyl or Cycloalkylalkanoylgruppe, wherein the above-mentioned Phenylkerne by a fluorine, chlorine or bromine atom, by a mono- or disubstituted methyl or methoxy group and the substituents equal o which may be different, a Alkylsultamgruppe having 3 to 5 carbon atoms in the alkyl moiety, optionally substituted by an alkyl or Hydroxycarbonylalkylgruppe pyrrolidino, piperidino or Hexamethyleniminogruppe, a pyrrolidinone, piperidinone or Hexamethyleniminongruppe, an optionally completely or partially hydrogenated phthalimido or a Group of formula in which
R₆, R₇ and R₈, which may be the same or different, are hydrogen atoms, alkyl groups having 1 to 8 carbon atoms, cycloalkyl, phenyl, cycloalkylalkyl or phenylalkyl groups or
R₇ is also a 2-chloro-ethyl, 2-bromo-ethyl, 3-chloro-propyl or 3-bromo-propyl group or
R₆ and R₇ together represent an ethylene or propylene group, wherein the above-mentioned phenyl nuclei may be mono- or disubstituted by hydroxy or alkoxy groups and the substituents may be identical or different, and, unless otherwise stated, the abovementioned alkyl, Alkoxy and alkanoyl moieties each containing 1 to 3 carbon atoms and the cycloalkyl moieties may each contain 5 to 7 carbon atoms,
R₂ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms,
R₃ is an alkyl group having 1 to 6 carbon atoms,
R₄ is a carboxy, cyano, 1H-tetrazolyl or 1-triphenylmethyl-tetrazolyl group or an alkoxycarbonyl group having a total of 2 to 5 carbon atoms and
R₅ represents a hydrogen, fluorine, chlorine or bromine atom,
their 1, 3-isomer mixtures, their Tautomre, their enantiomers and their addition salts with inorganic or organic acids or bases. 2. Heterocyclic imidazoles of the general formula I according to claim 1, in which
R₁ is a hydrogen, chlorine or bromine atom, a methyl, hydroxy, methoxy, ethoxy, 2-carboxymethyl-pyrrolidino, pyrrolidino, piperidino, methylpiperidino, 2-pyrrolidinone, 2-piperidinone or 2 Aminocarbonylcyclohexylcarbonylamino group, an amino or methylamino group optionally substituted on the nitrogen atom by an alkyl group having 1 to 4 carbon atoms, a cyclohexyl, cyclohexylmethyl, benzyl or dimethoxybenzyl group, an optionally substituted on the nitrogen atom by a cyclohexyl, cyclohexylmethyl, benzyl or dimethoxybenzyl group-substituted N-acylamino group in which the acyl part is an alkanoyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 2 to 4 carbon atoms in total, an alkylsulfonyl group having 1 to 4 carbon atoms, a cyclohexylcarbonyl or phenylalkanoyl group having 1 or 2 carbon atoms in the alkanoyl part, a Benzoyl, benzylsulfonyl, benzenesulfonyl or chlorophenylsulfonyl group, a Alkylsultam (1) group, an optionally fully or partially hydrogenated phthalimido group or a group of the formula in which
R₆, R₇ and R₈, which may be the same or different, are hydrogen atoms, alkyl groups having 1 to 6 carbon atoms, cyclohexyl, cyclohexylmethyl, benzyl, hydroxybenzyl, dihydroxybenzyl, methoxybenzyl or dimethoxybenzyl groups or
R₇ is also a 3-chloro-n-propyl group or
R₆ and R₇ together represent an n-propylene group,
R₂ is a hydrogen atom or a methyl group,
R₃ represents an n-propyl or n-butyl group,
R₄ represents a carboxy, methoxycarbonyl, tert.butoxycarbonyl, 1H-tetrazolyl or 1-triphenylmethyl-tetrazolyl group and
R₅ represents a hydrogen, chlorine or bromine atom,
their 1, 3-isomer mixtures, their tautomers, their enantiomers and their addition salts with organic or inorganic acids or bases. 3. Heterocyclic imidazoles of the general formula I according to claim 1, in which
R₁ is a hydrogen atom, an optionally substituted on the nitrogen atom by an alkyl group having 1 to 3 carbon atoms, by a cyclohexyl or benzyl substituted amino or N-acylamino group, in which the acyl radical is an alkanoyl group having 2 to 5 carbon atoms or a cyclohexylcarbonyl group, one optionally completely or partially hydrogenated phthalimido group or a group of the formula in which
R₈ represents a methyl, benzyl, hydroxybenzyl, dihydroxybenzyl, methoxybenzyl or dimethoxybenzyl group and
R₆ and R₇ together represent an n-propylene group,
R₂ is a hydrogen atom or a methyl group,
R₃ represents an n-propyl or n-butyl group,
R₄ is a carboxy or 1H-tetrazol-5-yl group and
R₅ is a hydrogen atom,
their 1, 3-isomer mixtures, their tautomers, their enantiomers and their addition salts with organic or inorganic acids or bases. 4. Heterocyclic imidazoles of the general formula I according to claim 1: 4 '- [(2-n-butyl-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-methyl-6-phthalimido-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-1 H -imidazo [4,5-c] pyridin-1-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-amino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-Benzylamino-8-n-butyl-9H-purin-9-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-methyl-6-propionylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-cyclohexylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-N-cyclohexylcarbonyl-ethylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5-methyl-6-valeroylamino-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid,
4 '- [(2-n-butyl-5- [3-benzyl-3,4,5,6-tetrahydro-2 (1H) pyrimidinone-3H-imidazo [4,5-b] pyridin-3-yl) methyl] biphenyl-2-carboxylic acid and
4 '- [(2-n-propyl-5- (2-methylpropionylamino) -3 H -imidazo [4,5-b] pyridin-3-yl) methyl] -2- (1H-tetrazole-5-yl) yl) biphenyl and their addition salts with inorganic or organic acids or bases. 5. Physiologically acceptable addition salts of the compounds according to at least one of claims 1 to 4 with inorganic or organic acids or bases. 6. A pharmaceutical composition containing a compound after at least one of claims 1 to 4 or a physiologically acceptable Addition salt according to claim 5, optionally one or more inert carriers and / or diluents. 7. Use of a compound according to at least one of the claims 1 to 5 for the manufacture of a medicament intended for the treatment of hypertension, heart failure, ischemic peripheral circulatory disorders, myocardial Ischemia (angina), for the prevention of heart failure progression after myocardial infarction, for the treatment of diabetic Nephropathy, glaucoma, gastrointestinal Diseases and bladder disorders is suitable. 8. A process for the preparation of a medicament according to claim 7, characterized in that non-chemical Ways a connection according to at least one of claims 1 to 5 in one or more inert carriers and / or Diluent is incorporated.   9. A process for preparing the heterocyclic imidazoles according to claims 1 to 5, characterized in that

• a) a compound of the general formula in the
  R₁, R₂ and A₁ to A₄ are as defined in claims 1 to 4,
  one of the radicals X₁ or Y₁ is a group of the general formula and the other of X₁ or Y₁ is a group of the general formula represent, wherein
  R₃ and R₅ are as defined in claims 1 to 4,
  R₉ represents a hydrogen atom or an R₃CO group, wherein R₃ is defined as mentioned above,
  Z₁ and Z₂, which may be the same or different, optionally substituted amino groups or optionally substituted by lower alkyl groups hydroxy or mercapto groups or
  Z₁ and Z₂ 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, but one of X₁ or Y₁ represents a group of the general formula must represent
  is cyclized or
• b) a compound of the general formula in the
  R₁ to R₃ and A₁ to A₄ are as defined in claims 1 to 4,
  with a biphenyl compound of the general formula in the
  R₄ and R₅ are as defined in claims 1 to 4 and
  Z₃ represents a nucleophilic leaving group such as a halogen atom or a substituted sulphonyloxy group,
  is implemented or
• c) for the preparation of a compound of the general formula I in which R₄ represents a carboxy group, a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined in claims 1 to 4 and
  R₄ "represents a group convertible into a carboxy group by hydrolysis, thermolysis or hydrogenolysis,
  is converted into a corresponding carboxy or
• d) for the preparation of a compound of the general formula I in which R₄ represents a 1H-tetrazolyl group, a protective group of a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined in claims 1 to 4 and
  R₄ "represents a 1H-tetrazolyl group protected in position 1 by a protecting group,
  is split off or
• e) for the preparation of a compound of the general formula I in which R₄ represents a 1H-tetrazolyl group, a compound of the general formula in the
  R₁ to R₃, R₅ and A₁ to A₄ are as defined in claims 1 to 4,
  is reacted with hydrazoic acid or
• f) for the preparation of compounds of general formula I in which R₁ represents an optionally substituted by an alkyl group having 1 to 6 carbon atoms, substituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl amino group, wherein, unless otherwise mentioned, the The above-mentioned alkyl moieties may each contain 1 to 3 carbon atoms and the cycloalkyl moieties may each contain 5 to 7 carbon atoms, a compound of the formula in the
  R₂ to R₅ and A₁ to A₄ are as defined in claims 1 to 4 and
  R₁₀ represents a group convertible by hydrolysis, hydrogenolysis or transamidation into an optionally substituted by an alkyl group having 1 to 6 carbon atoms, substituted by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, wherein, unless otherwise stated, the above-mentioned alkyl moieties each of 1 to 3 carbon atoms and the cycloalkyl moieties may each contain 5 to 7 carbon atoms,
  is converted into an appropriate connection or
• g) for the preparation of compounds of general formula I, in which R₁ is a group of the formula represents a compound of the formula in the
  R₂ to R₅ and A₁ to A₄ are as defined in claims 1 to 4 and
  R₁₁ represents a R₆NH group, wherein R₆ is as defined in claims 1 to 4, with a compound of formula in the
  R₇ and R₈ are as defined in claims 1 to 4,
  Z₄ a nucleophilic leaving group or
  Z₄ together with R₇ denote a nitrogen-carbon bond is reacted or
• h) for the preparation of compounds of general formula I in which R₁ represents an optionally substituted on the nitrogen atom by an alkyl group having 1 to 6 carbon atoms, by a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl substituted N-acylamino group, a compound of general formula in the
  R₂ to R₅ and A₁ to A₄ are as defined in claims 1 to 4 and
  R₁₂ is an amino group optionally substituted by an alkyl group having 1 to 6 carbon atoms, a phenyl, cycloalkyl, phenylalkyl or cycloalkylalkyl group, wherein, unless otherwise stated, the above-mentioned alkyl moieties each have 1 to 3 carbon atoms and the cycloalkyl moieties 5 respectively to 7 carbon atoms, with a compound of general formula R₁₃-W-OH (XII) in the
  W is a carbonyl or sulfonyl group,
  R₁₃ is an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 3 carbon atoms, a phenylalkyl, cycloalkyl or cycloalkylalkyl group each having 1 to 3 carbon atoms in the alkyl part and 5 to 7 carbon atoms in the cycloalkyl part, a phenyl, naphthyl, 2 Carboxy-cyclohexyl or 2-aminocarbonyl-cyclohexyl group, wherein the above-mentioned Phenylkerne by a fluorine, chlorine or bromine atom, mono- or disubstituted by a methyl or methoxy group and the substituents may be the same or different, or even if W represents a carbonyl group, a hydrogen atom, or acylated with their reactive derivatives such as their acid halides, acid esters or acid anhydrides, or
• i) for the preparation of a compound of the formula I in which R₆ and R₇ together represent an ethylene or n-propylene group, a compound of the formula in the
  R₂ to R₅, R₈ and A₁ to A₄ are as defined in claims 1 to 4,
  Hal is a chlorine, bromine or iodine atom and
  n represent the number 2 or 3, cyclized and, if necessary, subsequently with a compound of the formula R₈-Hal (XIV) in the
  R₈ is defined as excluding the hydrogen atom as defined in claims 1 to 4 and
  Hal represents a chlorine, bromine or iodine atom,
  is implemented and

If desired, then a thus obtained 1-, 3-isomer mixture of a compound of general formula I is separated by isomer separation in its 1- and 3-isomer, or
a racemate obtained in this way is separated into its enantiomers by means of enantiomer separation, or
a compound of general formula I thus obtained is converted into its addition salt, in particular for pharmaceutical use in its physiologically acceptable salt with an inorganic or organic acid or base.