Design, synthesis and anticonvulsant activity evaluation of 7-substituted-[1,2,4]-triazolo[4,3-f]pyrimidine derivatives.
In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED(50)) value of 34.7 mg/kg, median toxicity dose (TD(50)) of 262.9 mg/kg, and providing a protective index (PI=TD(50)/ED(50)) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide.
School of Food, Drug & Medicine Zhejiang Ocean University, Zhoushan 316000, PR China. glp730@yahoo.com.cn
Li-Ping
LP
Guan
Xin
X
Sui
Yue
Y
Chang
Zheng-Shun
ZS
Yan
Guo-Zhong
GZ
Tong
You-Le
YL
Qu
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D051379:Mice; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
D000927:Anticonvulsants; D002227:Carbazoles; D011743:Pyrimidines