Pharmakologisch wirksame Derivate von Phenylalkylaminen

摘要

1382821 Phenylalkylamines LILLY INDUSTRIES Ltd 7 Feb 1972 [8 Feb 1971] 4126/71 Heading C2C Phenylalkylamines of the general formula wherein m is 0 or 1, n is 1-6, each of R1 and R2 is a hydrogen atom or C 1-4 alkyl group, R3 is a hydrogen atom or, in no more than one instance in which it occurs, a C 1-4 alkyl group, R4 is a hydrogen atom or a C 1-4 alkyl group and R5 is a hydrogen atom or a C 1-4 alkyl, acetyl, hydroxyacetyl, trihaloacetyl, benzoyl, ethoxycarbonyl or -COCHR8R9 group (in which R8 is a hydrogenatom or methyl group and R9 is a 4-piperidinophenyl or 3-chloro-4-piperidinophenyl group), or R4R5N- is as R6, R6 is a pyrrolidino, piperidino, homopiperidino, piperazino, 4- methylpiperazino or morpholino group and R7 is a hydrogen or halogen atom or a methyl, methoxy, trifluoromethyl, nitro, amino, methylamino, dimethylamino or -NHCOR1 group, and acid addition salts thereof are prepared (a) when each of R4 and R5 is a hydrogen atom, by catalytic hydrogenation of the appropriate nitrile; (b) when each of R4 and R5 is a hydrogen atom, m + n = 2 and at least one of R1 and R2 is a hydrogen atom if m = 1, by reduction of the corresponding #-nitrostyrene; (c) when at least one of R4 and R5 is other than a hydrogen atom, by N-alkylation or -acylation of the corresponding compound in which R4 and/or R5 is a hydrogen atom; (d) when R5 is a hydrogen atom, by hydrolysis of the corresponding compound in which R5 is an acyl group; (e) when R4R5N- is as R6, by reaction of the corresponding compound in which each of R4 and R5 is a hydrogen atom with a suitable acyclic compound having terminal bromine atoms; followed optionally by salification of the product. The products are novel provided that each of R4 and R5 is a hydrogen atom or C 1-4 alkyl group only when each of R1 and R2 is a C 1-4 alkyl group and m is 1 or when the -NR4R5 group is separated from the phenyl ring by 4 or more carbon atoms. 4 - Piperidinophenylacetonitrile is prepared by reaction of 4-aminophenylacetontrile with 1,5 - dibromopentane. # - Nitro- 3 - chloro - 4- piperidinostyrene is prepared by reaction of 4- chloro-3-nitrobenzaldehyde with piperidine, reduction of the resulting 3-nitro-4-piperidinobenzaldehyde with stannous chloride in hydrochloric acid, diazotization of the resulting 3- amino - 4 - piperidinobenzaldehyde, followed by treatment with cuprous chloride in hydrochloric acid, and reaction of the resulting 3-chloro-4- piperidinobenzaldehyde with nitromethane in the presence of acetic acid and ammonium acetate. Pharmaceutical compositions having anorexic, anti-hallucinogenic, anti-Parkinson and antiinflammatory activity comprise, as active ingredient, a novel phenylalkylamine of the above general formula or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier, and may be administered orally, parenterally or rectally.