title: Design, synthesis of 6-substituted-pyrido[3,2-d]pyridazine derivatives with anticonvulsant activity.
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.
authors.forename: Zheng-Qi
authors.initials: ZQ
authors.lastname: Dong
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Region, 028002, China.. weichengxi1224@yahoo.com.cn.
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.affiliation: College of Pharmacy, Yanbian University, No. 977, GongYuan Road, Yanji City, Jilin Province 133000, China.. zsquan@ybu.edu.cn.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004597:Electroshock; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009068:Movement / Q000187:drug effects*; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D011724:Pyridazines; C000607215:pyrido(3,2-d)pyridazine