Synthesis and neuroleptic activity of benzamides. Cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds.

摘要: Three series of benzamides N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed synthesized as potential neuroleptics. All target compounds evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, a good correlation between structure activity was found throughout the series. In linear (analogues metoclopramide), introduction benzyl group terminal nitrogen, rather than an ethyl group, methyl p-amino metoclopramide both enhanced activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) about 15 times more active metoclopramide. cyclic series, particularly among 1-benzyl-3-aminopyrrolidine, most tested corresponding benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) all tested, being 13 408 potent haloperidol metoclopramide, respectively. Moreover, compound 55 exhibited fairly high ratio antistereotypic to cataleptogenicity compared with It is expected that may be used drug few side treatment psychosis.