Synthesis and pharmacological evaluation of some new dibenzo [b, f] [1, 4]thiazepines

Abstract

Aim

In the present study ten dibenzothiazepines with a methylene bridge between tricyclic nucleus and the substituent at C-11 were synthesized in order to investigate their antipsychotic activity. Some of the derivatives showed significant activity.

Methods

The title compounds were synthesized by condensation of 11-piperazinyl-dibenzothiazepine with the substituted benzyl halides in presence of triethylamine and 1,4-dioxane. The structures of the derivatives were elucidated by spectral analysis. The antipsychotic activity of the synthesized derivatives was evaluated using haloperidol induced catalepsy and lithium induced head twitches.

Results

In SSP-9 treated group, maximum catalepsy was noted 30 min after haloperidol. Lithium induced 40.2 ± 1.655 head twitches in 1 h. Clozapine (5 mg per kg) and SSP-9 (5 mg per kg) reduced the number of head twitches to 10 ± 0.7071 and 14.8 ± 0.8602, respectively.

Conclusion

The results demonstrated that the derivative SSP-9 possesses significant in vitro antipsychotic activity when compared with standard clozapine. Therefore, compound SSP-9 prototype could be considered as novel antipsychotic agent for further developing new atypical antipsychotics.