Design, Synthesis and Development of 5-[(4-Substituted) Phenyl]-3-Thioxo-2, 3-Dihydro-1H-2, 4-Benzodiazepin -1-Ones as Anticonvulsants

R. L. Sawant¹*, M. S. Bhatia¹ and Jyoti B. Wadekar²

¹P. D. V.V.P.F’s College of Pharmacy, Vilad-Ghat, Ahmednagar - 414 111 India. ²Bharti Vidyapeeth college of Pharmacy, Kolhapur - 416 013  India.

3-Thioxo-2,3-dihydro-1H-2,4-benzodiazepin-1-ones skeleton bearing 4-substituted phenyl ring at fifth position (2a-e) have been synthesized. The substituents at fourth position of the phenyl ring for initial and final set of compounds have been selected according to Topliss modified approach. The synthesized compounds were structurally characterized by TLC, elemental analysis, IR and NMR spectra studies. The anticonvulsant potential of synthesized compounds was evaluated by using Rotarod, Actophotometer and Electroconvulsometer. The anticonvulsant activity evaluation of initial set of compounds (2a-d) revealed that electron releasing substituents with high lipophilicity if placed at fourth position in phenyl ring should increase the anticonvulsant activity. Based on this observation, 4-dimethylamino substituted compound (2e) was synthesized and found to have increased activity.

Benzodiazepine; Topliss approach; Anticonvulsant activity