Patent GB-870385-A (GB)
Title: New benzimidazoles
Filed: 1958-10-14
Abstract: The invention comprises compounds of the general formula: <FORM:0870385/IV (b)/1> (wherein A represents a C1-5 alkylene radical, R represents a di-(C1-5 alkyl)-amino group, R1 and R3 each represent a C1-5 alkyl group, and R2 represents a hydrogen atom or a C1-5 alkyl group) and their physiologically tolerated acid addition salts, and pharmaceutical preparations containing these compounds (see Group VI).  The compounds may be prepared by (a) introducing a dialkylaminoalkyl group directly or in stages into the 1-position of a 2-(p-alkylbenzyl)-5-alkyl- or -5,6-dialkyl-benzimidazole, or (b) ring closure of a 2-(R11-NH)-5-alkyl- or -4,5-dialkyl-aniline (wherein R11 represents R-A-or a substituent replaceable, and subsequently replaced, thereby) by reaction with a p-alkylphenylacetic acid or a functional derivative thereof, or with a p-alkylphenylacetaldehyde or a functional derivative thereof with subsequent oxidation, or (c) forming a C1-5 alkyl group in the 5- or 5- and/or 6-position of a 1-dialkylaminoalkyl- 2-(p-alkylbenzyl)-benzimidazole or in the para-position of the benzyl radical of a 1-dialkylaminoalkyl-2-benzyl-5-alkyl- or -5,6-dialkyl-benzimidazole (e.g. by reduction of an alkanoyl or hydroxyalkyl group).  Free bases so obtained may be converted into acid addition salts and vice versa.  1-Dialkylaminoalkyl- 2-(p-alkylbenzyl)-5-hydroxyalkyl- and -5-carbalkoxy-benzimidazoles are prepared from the appropriate starting materials by processes analogous to (a) and (b) above. The 5-hydroxyalkyl compounds may alternatively be prepared by reduction of the 5-carbalkoxy compounds, and the latter by esterifying the corresponding 5-carboxy compounds or by reducing a hydroxyalkyl or alkanoyl group in the para-position of the benzyl radical of a 1-dialkylaminoalkyl-2-benzyl-5-carbalkoxybenzimidazole.  2-(b -Diethylaminoethylamino)- 5-methylani line is prepared by condensing 3-nitro-4-chlorotoluene with b -diethylaminoethylamine to form 2-(b -diethylaminoethylamino)-5-methyl-1-nitrobenzene and reducing the amino group with hydrogen in the presence of Raney nickel.  2 - (p-Methylbenzyl)- 5,6-dimethylbenzimidazole is prepared by refluxing 2-amino-4,5-dimethylaniline in chloroform with the iminoether hydrochloride of p-methylphenylacetic acid.  1 - (b -Diethylaminoethyl)- 2-(p-acetylbenzyl)-5-methylbenzimidazole is prepared by refluxing 2-(b -diethylaminoethylamino)-5-methylaniline in chloroform with the iminoether hydrochloride of p-acetylphenylacetic acid.ALSO:Pharmaceutical preparations comprise, in admixture with a pharmaceutical carrier for enteral, parenteral or topical administration, a benzimidazole derivative of the general formula <FORM:0870385/VI/1> (wherein A represents a C1-5 alkylene radical, R represents a di-(C1-5 alkyl)-amino group, R1 and R3 each represent a C1-5 alkyl group, and R2 represents a hydrogen atom or a C1-5 alkyl group) or a physiologically tolerated acid addition salt thereof (e.g. a hydrohalide, sulphate, nitrate, phosphate, thiocyanate, acetate, propionate, oxalate, malonate, succinate, malate or methane-, ethane-, hydroxyethane-, benzene- or toluene-sulphonate or a salt with a therapeutically active acid). The preparations may be in the form of tablets, dragees, salves, creams, solutions, suspensions or emulsions, which may be sterilized and/or may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure, buffers or other therapeutically valuable substances.