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Synthesis of 8-Alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and Evaluation of their Anticonvulsant Properties  

Sun, Xian-Yu (College of Pharmacy, Yanbian University)
Jin, Yun-Zhe (College of Pharmacy, Yanbian University)
Li, Fu-Nan (Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education)
Li, Gao (Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education)
Chai, Kyu-Yun (Department of Chemistry, Wonkwang University)
Quan, Zhe-Shan (Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education)
Publication Information
Archives of Pharmacal Research / v.29, no.12, 2006 , pp. 1080-1085 More about this Journal
Abstract
A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.
Keywords
Triazole[4,3-a]quinoline; Anticonvulsant; Maximal electroshock; Pentylenetetrazole; Neurotoxicity;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 21  (Related Records In Web of Science)
Times Cited By SCOPUS : 20
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