Premium
Synthesis and Anticonvulsant Activity Evaluation of 4‐Phenyl‐[1,2,4]triazolo[4,3‐ a ]quinazolin‐5(4 H )‐one and Its Derivatives
Author(s) -
Zhang HongJian,
Jin Peng,
Wang ShiBen,
Li FuNan,
Guan LiPing,
Quan ZheShan
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500115
Subject(s) - anticonvulsant , neurotoxicity , chemistry , ed50 , bicuculline , pharmacology , stereochemistry , toxicity , epilepsy , biochemistry , gabaa receptor , medicine , in vitro , organic chemistry , receptor , psychiatry
A series of 4‐(substituted‐phenyl)‐[1,2,4]triazolo[4,3‐ a ]quinazolin‐5(4 H )‐ones ( 6a–x ) with triazole and other heterocyclic substituents ( 7–14 ) were synthesized and the compounds were evaluated for their anticonvulsant activity and neurotoxicity by maximal electroshock (MES) and rotarod neurotoxicity tests. Among the compounds studied, 6o and 6q showed wide margins of safety with protective indices (PIs) that were much higher than those of currently used drugs (PI 6o > 25.5, PI 6q > 26.0). Compounds 6o and 6q showed significant oral activity against MES‐induced seizures in mice, with ED 50 values of 88.02 and 94.6 mg/kg, respectively. The two compounds were also found to have potent activity against seizures that were induced by pentylenetetrazole and bicuculline.