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

作者：Lv Zhiliang; Sheng Chunquan^*; Wang Tiantian; Zhang Yikai; Liu Jia; Feng Jilu; Sun Hailing; Zhong Hanyu; Niu Chunjuan; Li Ke

来源：Journal of Medicinal Chemistry, 2010, 53(2): 660-668.

DOI：10.1021/jm901237x

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 (IC(50) = 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.

• 出版日期2010-1-28
• 单位中国人民解放军第二军医大学