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

Abstract

Cyclic imides bearing ω-(4-benzisothiazol-3-yl-1-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.