Synthesis of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles as potential anticonvulsant agents.
A series of 2-substituted-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were synthesized. The anticonvulsant effect and neurotoxicity of the compounds (intraperitoneally) were evaluated with the maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests in mice. 2-Phenyl-6-(4H-1,2,4-triazol-4-yl)benzo[d]oxazole (3g) was the most active and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED(50)) of 29.5 mg/kg, a median toxicity dose (TD(50)) of 285 mg/kg, and a protective index (PI) of 9.7, which is greater than the reference drug, carbamazepine, which has a PI of 6.4.
Wei
Cheng-Xi
CX
Yanbian University, Yanji, Jilin, 133002, People's Republic of China.
Guan
Li-Ping
LP
Jia
Jing-Hao
JH
Chai
Kyu-Yun
KY
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001583:Benzoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002220:Carbamazepine / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D045442:Rotarod Performance Test; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*
D000927:Anticonvulsants; D001583:Benzoxazoles; D002220:Carbamazepine; D010433:Pentylenetetrazole