Psychotropic Agents. II. Synthesis and Psychotropic Activity of conformationally Restricted Butyrophenone Analogs

In order to search for new psychotropic agents, several conformationally restricted analogs (see Chart 1D) of haloperidol or benperidol were synthesized. cis-and trans-1-[2- (2-Phenylcyclopropyl) ethyl] piperidine derivatives (Xa, Xb, and XXIV) were prepared in several steps from the corresponding cis-and trans-1-phenyl-1-butene derivatives (III and XX). The effect of the compounds on spontaneous motor activity in mice was determined. trans-Isomer (Xb), which was the most active compound, was about 11 times more active than cis-isomer (XXIV). But the activity of Xb was about one-fifth as potent as benperidol. Structure-activity relationships of these compounds are discussed.