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Design, Synthesis of 6-Substituted-pyrido[3,2-d]pyridazine Derivatives with Anticonvulsant Activity

[ Vol. 11 , Issue. 6 ]

Author(s):

Zheng-Qi Dong, Xiao-Mei Liu, Cheng-Xi Wei and Zhe-Shan Quan   Pages 595 - 601 ( 7 )

Abstract:


Aim to find new compounds with stronger anticonvulsant activity and lower neurotoxicity, a novel series of 6-substituted-pyrido[3,2-d]pyridazine derivatives was synthesized using furo[3,4-b]pyridine-5,7-dione as the starting material. We evaluated their anticonvulsant activity and neurotoxicity using by maximal electroshock (MES) and rotarod neurotoxicity (TOX) tests. The results showed that N-m-chlorophenyl-[1,2,4]triazolo- [4,3-b]-pyrido[3,2- d]pyridazin-6-amine (3) was the most potent anticonvulsant, with ED50 value of 13.6 mg/kg and protective index ( PI = TD50/ED50) values of 7.2 in the MES test. Compound N-m-chlorophenyltetriazolo[5,1-b]-pyrido[3,2-d]pyridazin-6-amine (19), exhibited significant anticonvulsant activity in maximal electroshock test with PI value of 13.4, which was safer than marketed drug carbamazepine.

Keywords:

Pyrido[3, 2-d]pyridazine, anticonvulsant, maximal electroshock, neurotoxicity.

Affiliation:

Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Region, 028002, China., College of Pharmacy, Yanbian University, No. 977, GongYuan Road, Yanji City, Jilin Province 133000, China.

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