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

Author(s): Zheng-Qi Dong, Xiao-Mei Liu, Cheng-Xi Wei, Zhe-Shan Quan

Journal Name: Medicinal Chemistry

Volume 11 , Issue 6 , 2015


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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.

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Article Details

VOLUME: 11
ISSUE: 6
Year: 2015
Published on: 13 March, 2015
Page: [595 - 601]
Pages: 7
DOI: 10.2174/1573406411666150313152925
Price: $65

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