Metabolism of an atypical antipsychotic agent, 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2, 5,5-trimethyl-4-thiazolidinone (HP236).

Metabolism of an atypical antipsychotic agent, 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2, 5,5-trimethyl-4-thiazolidinone (HP236) by rats is described. HP236 was extensively metabolized both in vitro and in vivo. Metabolites were identified using electrospray interface-LC/MS (ESI-LC/MS) and 1H NMR spectroscopy.

Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate.

HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and evaluated in vitro for dopamine D2 and serotonin 5HT2 and 5HT1A receptor affinity. The compounds were examined in vivo in animal models of potential antipsychotic activity and screened in models predictive of extrapyramidal side effect (EPS) liability.

Benzisoxazole- and benzisothiazole-3-carboxamides as potential atypical antipsychotic agents.

A series of benzisoxazole- and benzisothiazole-3-carboxamides has been prepared and tested for potential antipsychotic activity. In general, the compounds showed an affinity for dopamine D2 and serotonin 5HT2A and 5HT1A receptors. Several members of this series have demonstrated activity in animal models predictive of potential antipsychotic activity.