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

2009; American Chemical Society; Volume: 53; Issue: 2 Linguagem: Inglês

10.1021/jm901237x

1520-4804

Zhiliang Lv, Chunquan Sheng, Tiantian Wang, Yikai Zhang, Jia Liu, Ji-Lu Feng, Hai-Ling Sun, Hanyu Zhong, Chunjuan Niu, Ke Li,

Cancer therapeutics and mechanisms

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 6l, with good inhibitory activity against HBV DNA replication (IC(50) = 0.206 and 0.12 microM, 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.