Synthesis of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinolin-1(2H)-ones with anticonvulsant activity.
A series of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2H)-ones was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, 2-propionyl-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one 4b was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED(50)) of 8.2 mg/kg, median toxicity dose (TD(50)) of 318.3 mg/kg, and the protective index (PI) of 39.0 which is much greater than the PI of the reference drugs phenytoin and carbamazepine.
Wei
Cheng-Xi
CX
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin, PR China.
Li
Fu-Nan
FN
Zhao
Long-Xuan
LX
Zhao
Li-Ming
LM
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D015363:Quinolones