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

Hussein I. El-Subbagh, Ghada S. Hassan, Adel S. El-Azab, Alaa A.M. Abdel-Aziz, Adnan A. Kadi, Abdulrahman M. Al-Obaid, Othman A. Al-Shabanah, Mohamed M. Sayed-Ahmed

Research output: Contribution to journalJournal articlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5567-5572
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Anticonvulsant activity
  • Benzo[d] oxazolo[5,2-a][12,6]diazepine
  • Benzo[d]thiazolo[5,2-a][12,6] diazepine
  • Synthesis
  • Thiazolo[3,2-a][1,3]diazepine

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