Synthesis and anticonvulsant activity of 1-substituted-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline.
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 ED50 in the MES and scMet tests was 17.3 and 24 mg.kg-1, respectively. The safest compound was 4 g, 1-phenyl-7-benzyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline, with TD50 and protective index (PI) (PI=TD50/ED50) values of greater than 300 mg.kg-1 and 13, respectively. The PI value of compound 4 g was better than that of most marketed drugs. Structure-activity relationships are also described in this paper.
College of Pharmacy, Yanbian University, Jilin, P. R. China.
Li-Jing
LJ
Cui
Zhi-Feng
ZF
Xie
Hu-Ri
HR
Piao
Gao
G
Li
Kyu-Yun
KY
Chai
Zhe-Shan
ZS
Quan
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D000927:Anticonvulsants; D015363:Quinolones