GB1078251A - Benzimidazolone derivatives - Google Patents

Abstract

Compounds of the formula <FORM:1078251/C2/1> wherein R represents a straight or branched alkylene radical with from 2 to 4 carbon atoms; R1 represents a hydrogen atom or taken together with R2, an alkylene radical with from 2 to 4 carbon atoms; R2 represents, in addition, an alkyl radical with 1 to 3 carbon atoms or together with R3 an alkylene radical with 4 to 6 carbon atoms; R3 represents, in addition, a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms; R4 which is in the 5- or 6-position, represents a hydrogen atom, a halogen atom or an alkyl radical containing from 1 to 3 carbon atoms; and R5 represents a hydrogen atom, a halogen atom or an alkyl radical containing 1 to 3 carbon atoms and pharmaceutically acceptable acid addition salts thereof and the preparation thereof: (a) by reacting a compound of the formula <FORM:1078251/C2/2> wherein R4 and R5 have the above significance with a reactive ester derived from an alcohol of the formula <FORM:1078251/C2/3> wherein R, R1, R2 and R3 have the above meaning, in an inert solvent after prior or with simultaneous exposure to a condensing agent such as an alkali metal or compounds thereof, e.g. the amide or alkoxide; (b) by condensing a compound of the formula <FORM:1078251/C2/4> wherein R, R1, R2, R3, R4 and R5 have the above significance, with a reactive derivative of carbonic acid, e.g. urea; (c) when R1 in the first general formula above is hydrogen, either by treating reactive esters derived from alcohols of the formula <FORM:1078251/C2/5> wherein R, R4 and R5 have the above meaning with a suitably substituted amine, or by alkylating primary amines of the formula <FORM:1078251/C2/6> wherein R, R4 and R5 are as above; and, finally, (d) when R4 and/or R5 in the first general formula above denote halogen, by diazotizing the corresponding compounds, in which R4 and/or R5 are amino groups and subsequently converting the resulting diazonium compounds to the desired halogen substituted products, e.g. by the Sandmeyer reaction. Pharmaceutical compositions suitable for enteral or parenteral administration, which are useful as anti-depressants or anti-convulsants, contain as the active principle one or more compounds of the first general formula above or pharmaceutically acceptable acid addition salts thereof in an inert carrier. Substituted benzimidazolones corresponding to the second general formula above are obtained by condensing compounds of the formula <FORM:1078251/C2/7> wherein R4 and R5 have the above significance, with a reactive derivative of carbonic acid, e.g. phosgene. Esters derived from alcohols of the fifth general formula above are obtained by treating compounds corresponding to the second general formula above with a mixed di-ester of an alkylene glycol, an alkylene oxide or an alkylene halhydrin or the tetrahydropyranyl ether thereof. 1 - Phenyl - 3 - (b - dimethylaminoethyl)-, 1 - phenyl - 3 - (g - dimethylaminopropyl)-, 1-phenyl - 3 - (11 - methyl - piperidyl - 31 - methyl)- 6 - chloro -, 1 - phenyl - 3 - (g - dimethylaminopropyl) - 6 - chloro - and 1 - p - chlorophenyl - 3 - (g - pyrrolidin - 11 - yl - propyl) - benzimidazolones are prepared among others using the above methods.