Synthesis and anticonvulsant activity of some new thiazolo(3,2-a)(1,3)diazepine, benzo(d)thiazolo(5,2-a)(12,6)diazepine and benzo(d)oxazolo(5,2-a)(12,6)diazepine analogues.

摘要

A new series of 6,7-dihydro-thiazolo[3,2-a][1,3]diazepines (9-12), benzo[d]thiazolo[5,2-a][12,6]diazepines (19-21) and benzo[d]oxazolo[5,2-a][12,6]diazepine (24) analogues were synthesized and evaluated for their anticonvulsant activity. Compounds (E)-2-bromo-6,7-dihydro-thiazolo[3,2-a][1,3]diazepine-8(5H)-thione (12), 3-chloro-benzo[d]thiazolo[5,2-a][12,6]diazepin-10-one (20), and 4-chloro-benzo[d]oxazolo[5,2-a][12,6] diazepin-10-one (24) showed 100% protection against PTZ- and bicuculline-induced seizures; 70%, 33%, 70% protection against MES-induced tonic extension; and 70%, 66%, 100% protection against picrotoxin-induced convulsions, respectively. Compounds 12, 20, and 24 proved to act as GABA(A) receptor agonists, with ED(50) values of 252, 380, 251 mg/kg; TD(50) values of 398, 417, 355 mg/kg; PI values of 1.58, 1.09, 1.41; LD(50) values of 380, 617, 537 mg/kg and TI values of 1.51, 1.62, 2.14, respectively.