title: 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.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University, Cairo 12311, Egypt. subbagh@yahoo.com
authors.forename: Hussein I
authors.initials: HI
authors.lastname: El-Subbagh
authors.forename: Ghada S
authors.initials: GS
authors.lastname: Hassan
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Kadi
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Al-Obaid
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D001381:Azepines; D010433:Pentylenetetrazole