Synthesis and Anticonvulsant Activity of 1-Substituted-7-Benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline(Medicinal Chemistry)

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Starting from 6-hydroxy-3,4-dihydro-1H-quinoline-2-one, a series of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines was synthesized and their structures were characterized using IR, ^1H-NMR, MS, and elemental analysis techniques. Anticonvulsant activity was evaluated in the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scMet) test, and rotarod neurotoxicity test. The most active compound was 7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline 4a. Its ED_<50> in the MES and scMet tests was 17.3 and 24mg・kg^<-1>, respectively. The safest compound was 4g, 1-phenyl-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline, with TD_<50> and protective index (PI)(PI=TD_<50>/ED_<50>) values of greater than 300mg・kg^<-1> and 13, respectively. The PI value of compound 4g was better than that of most marketed drugs. Structure-activity relationships are also described in this paper.
社団法人日本薬学会の論文
2005-07-01