Synthesis of 6-Alkyloxyl-3,4-dihydro-2(1H)-quinoliones and Their Anticonvulsant Activities

Bulletin of the Korean chemical society

Jun-Min Wang¹  Kyu-Yun Chai¹  Kyung-Chell Kwak¹  Jung-Rae Rho¹  Chang-Soo Jun¹  Hee-Cheol Kang¹  Zhe-Shan Quan¹ 

关键词: [1;    2;    4]Triazolo[4;    3-a]quinoline;    Anticonvulsant;    Maximal electroshock;    Pentylenetetrazole;    Neurotoxicity;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

A series of 6-alkyloxyl-3,4-dihydro-2(1H)-quinoliones (5a-5n) were synthesized through nitration, reduction, diazotization, hydrolysis and alkylation from 3,4-dihydro-2(1H)-quinolione. Their structures were characterized by IR, 1H-NMR and MS. The anticonvulsant activity was evaluated by the Maximal electroshock test (MES) and the subcutaneous pentylenetetrazole (Metrazole) test (sc-Met). The neurotoxicity was measured by the Rotarod test (Tox). The result showed that 6-hexyloxy-3,4-dihydro-2 (1H)-quinolinone (5c) was potent in anti-MES and anti-scMet test with ED50 of 24.0 mg/kg and 21.2 mg/kg, respectively, albeit its TD50 (67.6mg/kg) revealed the high neurotoxicity. 6-Benzyloxy-3,4-dihydro-2(1H)-quinolinone (5f) was less effective against MES induced seizure with ED50 of 29.6 mg/kg, but no neurotoxicity was observed even under 300 mg/kg. Its Protective index (PI) was greater than 10 preferable to Phenytoin, Carbamazepin, Phenobarbital and Valproate.

【 授权许可】

Unknown