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.
Institute of Neurosurgery, Inner Mongolia University for Nationalities, Tongliao, China.
Cheng-Xi
CX
Wei
Xian-Qing
XQ
Deng
Kyu-Yun
KY
Chai
Zhi-Gang
ZG
Sun
Zhe-Shan
ZS
Quan
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