GB1377231A — Basically substituted benzyl-phthalazinone derivatives acid addition salts thereof and process for the production thereof

USPTO Abstract

1377231 4 - Benzyl - 1(2H) - phthalazinones ASTA-WERKE AG CHEMISCHE FABRIK 12 Jan 1972 [22 Jan 1971] 1433/72 Heading C2C Novel 4 - benzyl - 1(2H) - phthalazinones of the general formula wherein each of R 1 and R 2 is a hydrogen or halogen atom or a C 1-4 alkyl, C 1-4 alkoxy, hydroxy, trifluoromethyl, nitro or optionally substituted amino group; X is -CH 2 - or -CH(CH 3 )-, m and n are each 1, 2 or 3, p is 0 or 1 and -CH=Y is an N-C 1-4 alkyl-pyrrolidinyl, N-C 1-4 alkyl-piperidyl, N-C 1-4 alkyl. perhydroazepinyl, quinuclidinyl, tropanyl or scopyl group, the tropanyl or scopyl group being connected to the 2-nitrogen atom of the phthalazinone directly by way of a ring carbon atom of this tropanyl or scopyl group, and the other groups being connected to the 2-nitrogen atom of the phthalazinone directly or by way of a -CH 2 - or -CH(CH 3 )- group, and physiologically acceptable acid addition salts thereof are prepared (a) by reacting an α-phenyl-acetophenone-o-carboxylic acid of the general formula or a reactive derivative thereof with a hydrazine of the general formula H 2 N-NHR 3 , wherein R 3 is a hydrogen atom or group; (b) by reacting an α-phenyl-acetophenone of the general formula with a hydrazine of the general formula wherein R 4 is a C 1-4 alkyl group; (c) by reacting a hydrazide of the general formula with a phenylacetic acid or derivative thereof of the general formula wherein Z is a halogen atom or a hydroxy or alkoxy group; or (d) when -CH=Y is an N-C 1-4 alkyl-pyrrolidinyl, N-C 1-4 alkyl-piperidyl or N-C 1-4 alkyl-perhydroazepinyl group, by alkylating the corresponding compound in which -CH=Y is a pyrrolidinyl, piperidyl or perhydroazepinyl group; and reacting a benzylphthalazinone of the general formula wherein R 3 is a hydrogen atom, resulting from (a), (b) or (c), with a compound of the general formula Q-R 3 , wherein Q is an atom or group which, upon substitution of the amide group, is split off together with its electron doublet, and R 3 is -(X) p -CH=Y, and optionally converting the resulting benzyl-phthalazinone into a physiologically acceptable acid addition salt thereof or optionally converting a resulting salt of a benzyl-phthalazinone into the free base. Pharmaceutical compositions having histaminolytic activity comprise, as active ingredient, a 4-benzyl-1(2H)-phthalazinone of the first general formula above or a physiologically acceptable acid addition salt thereof, together with a suitable carrier.