6-氯-4-(2-氯苯基)-3-(2-羟乙基)喹啉-2(1H)-酮衍生物作为新型非核苷类抗乙型肝炎病毒药物的构效关系研究。
Structure-activity relationships study of 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives as novel non-nucleoside anti-hepatitis B virus agents.
机构信息
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China.
出版信息
Eur J Med Chem. 2011 Jan;46(1):307-19. doi: 10.1016/j.ejmech.2010.11.019. Epub 2010 Nov 19.
A series of novel 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives were synthesized and evaluated for anti-hepatitis B virus (anti-HBV) activities in vitro to explore their structure-activity relationships (SARs). Most of the synthesized compounds possessed potent anti-HBV activity, of which the promising compound 44 exhibited significantly inhibitory potency against the secretion of hepatitis surface antigen (HBsAg) (IC(50) = 0.010 mM, SI > 135), hepatitis e antigen (HBeAg) (IC(50) = 0.026 mM, SI > 51) and the replication of HBV DNA (IC(50) = 0.045 mM). Preliminary mechanism study suggested compound 44 could mainly enhance the transcript activity of HBV ENI (enhancer I), EN-II (enhancer II).
一系列新型 6-氯-4-(2-氯苯基)-3-(2-羟乙基)喹啉-2(1H)-酮衍生物被合成并在体外评估其抗乙型肝炎病毒（抗 HBV）活性，以探索其构效关系（SAR）。大多数合成的化合物具有很强的抗 HBV 活性，其中有前途的化合物 44 对乙型肝炎表面抗原（HBsAg）的分泌表现出显著的抑制作用（IC（50）=0.010mM，SI>135）、乙型肝炎 e 抗原（HBeAg）（IC（50）=0.026mM，SI>51）和 HBV DNA 的复制（IC（50）=0.045mM）。初步的机制研究表明，化合物 44 主要可以增强 HBV ENI（增强子 I）、EN-II（增强子 II）的转录活性。
Zotero 插件