Patent IL-114996-A (IL)
Title: 1-biphenylimidazole derivatives, processes for the preparation thereof, and pharmaceutical compositions containing the same
IPC: A61K/
Filed: 1992-02-21
Abstract: Angiotensin II receptor antagonistic compounds of the formula: R2R3 N R1OR4 N CH2R5 R6R7 in which R1 represents an alkyl group having from 1 to 6 carbon atoms or an alkenyl group having from 3 to 6 carbon atoms; R2 and R3 are the same or different and each represents: a hydrogen atom; an alkyl group having from 1 to 6 carbon atoms; an alkenyl group having from 3 to 6 carbon atoms; a cycloalkyl group having a total of from 3 to 10 carbon atoms in one or more saturated carbocyclic rings; an aralkyl group in which the alkyl part has from 1 to 6 carbon atoms and the aryl part is as defined below; an aryl group as defined below; or a fused ring system in which an aryl group, as defined below, is fused to a cycloalkyl group having from 3 to 10 carbon atoms; R4 represents: a hydrogen atom; an alkyl group having from 1 to 6 carbon atoms; an alkanoyl group having from 1 to 6 carbon atoms; a substituted alkanoyl group having from 2 to 6 carbon atoms and substituted by at least one substituent selected from halogen atoms and alkoxy groups having from 1 to 6 carbon atoms; an alkenoyl group having from 3 to 6 carbon atoms; an arylcarbonyl group in which the aryl part is as defined below; an alkoxycarbonyl group in which the alkyl part has from 1 to 6 carbon atoms; a tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl or tetrahydrofuryl group; a substituted tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrothienyl or tetrahydrofuryl group which is substituted by at least one substituent selected from halogen atoms and alkoxy groups having from 1 to 6 carbon atoms; a group of formula -SiRaRbRc, in which 1, 2 or 3 of the groups represented by Ra, Rb and Rc are the same or different and each represents an alkyl group having from 1 to 6 carbon atoms, and 2, 1 or 0 of the groups represented by Ra, Rb and Rc are the same or different and each represents an aryl group, as defined below; an alkoxymethyl group in which the alkoxy part has from 1 to 6 carbon atoms; an (alkoxyalkoxy) methyl group in which each alkoxy part has from 1 to 6 carbon atoms; a haloalkoxymethyl group in which the alkoxy part has from 1 to 6 carbon atoms; an aralkyl group, in which an alkyl group having from 1 to 6 carbon atoms is substituted by at least one aryl group, as defined below; or an alkanoyloxymethoxycarbonyl group in which the alkanoyl part has from 1 to 6 carbon atoms; R5 represents a carboxy group or a group of formula -CONR8R9, in which R8 and R9 are the same or different and each represents a hydrogen atom, an unsubstituted alkyl group having from 1 to 6 carbon atoms, or a substituted alkyl group which has from 1 to 6 carbon atoms and which is substituted by at least one of substituents (a), defined below, or R8 and R9 together represents an unsubstituted alkylene group having from 2 to 6 carbon atoms or a substituted alkylene group which has from 2 to 6 carbon atoms or a substituted alkylene group which has from 2 to 6 carbon atoms and which is substituted by at least one substituent selected from carboxy groups and alkoxycarbonyl groups in which the alkyl part has from 1 to 6 carbon atoms; R6 represents a hydrogen atom, an alkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 1 to 6 carbon atoms or a halogen atom; R7 represents a carboxy group or a tetrazol-5-yl group; said substituents (a) are selected from: aryl groups as defined below; heterocyclic groups having 5 or 6 ring atoms, or which from 1 to 4 are nitrogen and/or oxygen and/or sulfur hetero-atoms; halogen atoms; hydroxy groups; alkoxy groups having from 1 to 6 carbon atoms; carboxy groups; alkoxycarbonyl groups in which the alkyl part has from 1 to 6 carbon atoms; amino groups; and acylamino groups, in which the acyl part is an alkanoyl group having from 1 to 6 carbon atoms or an arylcarbonyl group, in which the aryl part is as defined below; said aryl groups are aromatic carbocylic groups which have from 6 to 14 ring atoms and which are unsubstituted or are substituted by at least one of substituents (b), defined below; and said substituents (b) are selected from nitro groups, cyano groups, halogen atoms, unsubstituted carbocyclic aryl groups having from 6 to 10 ring atoms, alkyl groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, alkoxy groups having from 1 to 6 carbon atoms, carboxy groups, alkoxycarbonyl groups in which the alkoxy part has from 1 to 6 carbon atoms and alkylenedioxy and alkylidenedioxy groups having from 1 to 3 carbon atoms; and pharmaceutically acceptable salts and esters thereof; with the proviso that at least one of R2 and R3 is a hydrogen atom; and with the exclusion of compounds and pharmaceutically acceptable salts thereof, wherein: R1 is an alkyl group of 2 to 6 carbon atoms or an alkenyl group of 3 to 6 carbon atoms; R2 is a hydrogen atom; R3 is a hydrogen atom, an alkyl group of 1 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, a phenyl group or a benzyl group; R4 is a hydrogen atom, an alkyl group of 1 to 6 carbon atoms or a benzyl group; R5 is a carboxy group or an ester thereof of formula -COORA £where RA is an alkyl group of 1 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, a phenyl group or a benzyl group|, or a group -CONR8R9, where R8 and R9 are each a hydrogen atom, an unsubstituted alkyl group of 1 to 4 carbon atoms, a benzyl group, an a-methylbenzyl group, or R8 and R9 together form an unsubstituted C4 or C5 alkylene group; R6 is a hydrogen atom, an alkyl group of 1 to 4 carbon atoms, an alkoxy group of 1 to 4 carbon atoms, or a halogen atom; R7 is a carboxy group or a tetrazol-5-yl group; however, including and not excluding compounds of formula (I), in which: R1 represents an ethyl, propyl or butyl group; R2 represents a hydrogen atom or a methyl group and R3 represents a hydrogen atom; R4 represents a hydrogen atom or a methyl group; R5 represents a group of formula -COOR5a, in which R5a represents a hydrogen atom, a pivaloyloxymethyl group, an ethoxycarbonyloxymethyl group, a 1-(ethoxycarbonyloxy) ethyl group, an isopropoxycarbonyloxymethyl group, a 1-(isopropoxycarboyloxy) ethyl group, a (5-methyl-2-oxo-1, 3-dioxolen-4-yl) methyl group, or a phthalidyl group; R6 represents a hydrogen atom; R7 represents a carboxy group or a tetrazol-5-yl group at the 2-position of the benzene ring; and the benzene ring which bears the substituents represented by R6 and R7 is at the 4-position of the benzyl group to which it is attached.