title: Design, synthesis, and antihepatitis B virus activities of novel 2-pyridone derivatives.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Lv
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Tiantian
authors.initials: T
authors.lastname: Wang
authors.forename: Yikai
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Jilu
authors.initials: J
authors.lastname: Feng
authors.forename: Hailing
authors.initials: H
authors.lastname: Sun
authors.forename: Hanyu
authors.initials: H
authors.lastname: Zhong
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Niu
authors.forename: Ke
authors.initials: K
authors.lastname: Li
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D015195:Drug Design; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D011728:Pyridones; C017679:2-hydroxypyridine