4-Piperazinyl-10H-thieno[2,3-b][1,5]benzodiazepines as potential neuroleptics

Abstract

A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.