Design, Synthesis, and Antihepatitis B Virus Activities of Novel 2-Pyridone Derivatives

被引：103

作者：

Lv, Zhiliang ^{[1
]}

Sheng, Chunquan ^{[1
]}

Wang, Tiantian ^{[1
]}

Zhang, Yikai ^{[1
]}

Liu, Jia ^{[1
]}

Feng, Jilu ^{[1
]}

Sun, Hailing ^{[1
]}

Zhong, Hanyu ^{[1
]}

Niu, Chunjuan ^{[1
]}

Li, Ke ^{[1
]}

机构：

[1] Second Mil Med Univ, Dept Med Chem, Coll Pharm, Shanghai 200433, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 02期

关键词：

CHRONIC HEPATITIS-B; CONSENSUS DEVELOPMENT CONFERENCE; LAMIVUDINE THERAPY; RESISTANCE; INFECTION; DISEASE;

D O I：

10.1021/jm901237x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 2-pyridone derivatives were synthesized and evaluated for their antihepatitis B virus (HBV) activity and cytotoxicity in vitro. Moderate to good activity against HBV DNA replication was observed in these 2-pyridone analogues. The most active compounds were 5d and 61, with good inhibitory activity against HBV DNA replication (IC50 = 0.206 and 0.12 mu M, respectively) and remarkable high selectivity (selectivity indexes of >532 and 467, respectively). A pharmacophore model of the synthesized compounds was proposed by the GASP program. The pharmacophore model consists of three hydrophobic points, four HBA points, and one HBD point. The 2-pyridone derivatives represent a novel class of HBV inhibitors, which are worth further optimization.

引用

页码：660 / 668

页数：9

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