Synthesis And Anticonvulsant Activity Of A New 6-Alkoxy-[1,2,4] Triazolo [4,3-b] Pyridazine | Posted on:2012-11-20 | Degree:Master | Type:Thesis | Country:China | Candidate:X Sui | Full Text:PDF | GTID:2214330338473491 | Subject:Medicinal chemistry | Abstract/Summary: | PDF Full Text Request | A series of 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine derivatives were synthesized. In initial screening and quantitative evaluation, compound 2r was among the most active agents, exhibiting in the same time the lowest toxicity. In the anti-maximal electroshock test, it showed median effective dose (ED50) of 17.3 mg/kg and median toxicity dose (TD50) of 380.3 mg/kg, and the protective index (PI) of 22.0, which is much better than PI of the reference drugs. In a subsequent test, compound 2r had median hypnotic dose (HD50) of 746.6 mg/kg, thus demonstrating much better margin of safety compared to reference drugs. Compound 2r also showed oral activity against MES-induced seizures and lower oral neurotoxicity. For explanation of the putative mechanism of action, compound was tested in chemical induced models. | Keywords/Search Tags: | [1,2,4]Triazolo[4,3-b]pyridazine, Anticonvulsant activity, Maximal electroshock test, Neurotoxicity, Chemical induced models | PDF Full Text Request | Related items |
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