Succinimide Derivatives. II.1) Synthesis and Antipsychotic Activity of N-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl] butyl]-1,2-cis-cyclohexanedicarboximide (SM-9018) and Related Compounds2,3)

Abstract

Cyclic imides bearing ω-(4-benzisothiazol-3-yl-l-piperazinyl)alkyl moieties were synthesized and tested for antipsychotic activity. The in vitro binding affinities of these compounds were examined for dopamine 2 (D2) and serotonin 2 (5-HT2) receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, N-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl] butyl]-1,2-cis-cyclohexanedicarboximide (SM-9018), was found to be more potent and more selective in vivo than tiospirone in its antipsychotic activity. SM-9018 (17) is currently undergoing clinical evaluation as a selective antipsychotic agent. © 1995, The Pharmaceutical Society of Japan. All rights reserved.