title: Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents.
abstract: A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a-5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED50 value of 6.20 mg/kg (oral/rat) and a protective index (PI = ED50/TD50) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5 b, 5 c, 5 i and 5 o, their influence on sodium channel was evaluated in vitro.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi , India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Malik
authors.forename: Suroor A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004597:Electroshock; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D015222:Sodium Channels / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014227:Triazines
keywords: 1, 2, 4-triazine; Anticonvulsant activity; benzisoxazole; in vitro studies; sodium channels