Design, synthesis and anticonvulsant activity evaluation of 7-substituted-[1,2,4]-triazolo[4,3-f]pyrimidine derivatives.

Abstract

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.

• Authors: Li-Ping Guan, Xin Sui, Yue Chang, Zheng-Shun Yan, Guo-Zhong Tong, You-Le Qu
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 8 Issue 6 Pg. 1076-83 (Nov 2012) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 22779795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Carbazoles
• Pyrimidines

Topics

• Animals
• Anticonvulsants (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Carbazoles (adverse effects, chemistry)
• Chemistry Techniques, Synthetic
• Drug Design
• Mice
• Pyrimidines (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Seizures (chemically induced, drug therapy)