Synthesis and anticonvulsant evaluation of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazoles as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines.
A series of 4-(4-alkoxylphenyl)-3-ethyl-4H-1,2,4-triazole derivatives was synthesized as open-chain analogues of 7-alkoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES test) and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). MES test showed that 3-ethyl-4-(4-octyloxyphenyl)-4H-1,2,4-triazole 3q was found to be the most potent with ED(50) value of 8.3mg/kg and protective index (PI=TD(50)/ED(50)) value of 5.5, but compound 3r, 3-ethyl-4-(4-octyloxyphenyl)-4H-1,2,4-triazole, exhibited better PI value of 9.3, which was much greater than PI value of the prototype drug phenytoin. For explanation of the possible mechanism of action, the compound 3r was tested in pentylenetetrazole test, isoniazid test, thiosemicarbazide test, 3-mercaptopropionic acid and strychnine test.
Chen
Jing
J
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Yanbian University, Ministry of Education, Yanji, Jilin, China.
Sun
Xian-Yu
XY
Chai
Kyu-Yun
KY
Lee
Jin-Seok
JS
Song
Mi-Sun
MS
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced; D013331:Strychnine / Q000633:toxicity; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C525230:3-ethyl-4-(4-octyloxyphenyl)-4H-1,2,4-triazole; D000927:Anticonvulsants; D011804:Quinolines; D014230:Triazoles; D013331:Strychnine