Synthesis and anticonvulsant activity of 1-formamide-triazolo[4,3-a]quinoline derivatives.
Using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material, a series of 1-formamide-triazolo[4, 3-a]quinoline derivatives (6a-6n) was synthesized, the anticonvulsant effect and neurotoxicity of the compounds was calculated with maximal electroshock test and rotarod tests with intraperitoneally injected in KunMing mice. The results demonstrated that compound 7-(hexyloxy)-4,5-dihydro-[1,2,4] triazolo[4,3-a]quinoline-1-carboxamide (6d) was the most active one and also had the lowest toxicity. In the anti-maximal electroshock potency test, it showed median effective dose (ED(50)) of 30.1 mg/kg, median toxicity dose (TD(50)) of 286 mg/kg, and the protective index of 9.5 which is greater than the reference drug carbamazepine with the protective index value of 6.0.
Wei
Cheng-Xi
CX
Institute of Neurosurgery, Inner Mongolia University for Nationalities, Tongliao, China.
Deng
Xian-Qing
XQ
Chai
Kyu-Yun
KY
Sun
Zhi-Gang
ZG
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D045442:Rotarod Performance Test
D000927:Anticonvulsants; D011804:Quinolines; D002220:Carbamazepine