Synthesis, preliminary anticonvulsant and toxicity screening of substituted 3-(Dimethyl/Diethylamino)-{1-[4-methyl-2-substitutedphenyl-2,5-dihydro-1,5-benzothiazepin-3-yl]}propan-1-one

Abstract

Background; 1,5-benzothiazepine moiety is a very important pharmacophore bioactive compound that exhibits different biological activities. By the literature review the basic structure requirements for anticonvulsant activity contains molecular weight less than 500, Oil/water distribution coefficient is less than 5, Hydrogen bond donors more than 5 and Hydrogen bond acceptor more than 10. Aim of study: Aim of the study is to synthesize a novel series of 1,5-benzothiazepine nucleus containing Mannich bases which retained anticonvulsant biological activities with less toxic effect. Materials & methods: We synthesized successfully various substituted 3-(Dimethyl/Diethylamino)-{1-[4-Methyl-2 substitutedphenyl-2,5-dihydro-1,5 benzothiazepin-3-yl]}propan-1-one (6a-6t). Completion of chemical reaction was monitored by thin layer chromatography on silica gel G coated plates and final compounds were purified by recrystallisation with methanol. The chemical structure of synthesized compounds confirmed by chromatographi, electro analytical and physiochemical analysis. Results & discussion: All the novel synthesized compounds screened by anticonvulsant activity by maximum electroshock induced seizure against Phenytoin as standard. All the synthesized compounds showed significant anticonvulsant activity. The most potent significant compound was found 3-(Dimethylamino)-{1-[3-chlorophenyl-4-methyl-2, 5-dihydro-1,5-benzothiazepin-3-yl]}propan-1-one (6e). Further, preliminary safety profile of most potent significant compound 6e was evaluated by acute oral toxicity and neurotoxicity testing.