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

  • Eur J Med Chem. 2011 Jan;46(1):307-19. doi: 10.1016/j.ejmech.2010.11.019.
Rui-Hua Guo  1 ,  Quan Zhang ,  Yun-Bao Ma ,  Jie Luo ,  Chang-An Geng ,  Li-Jun Wang ,  Xue-Mei Zhang ,  Jun Zhou ,  Zhi-Yong Jiang ,  Ji-Jun Chen
Affiliations
  • 1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, PR China.
PMID: 21145140 DOI: 10.1016/j.ejmech.2010.11.019
Abstract

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).