title: Study on 2-arylthio-5-iodo pyrimidine derivatives as novel nonnucleoside inhibitors against hepatitis B virus DNA replication.
abstract: Novel nonnucleoside hepatitis B virus inhibitors have been recently developed for the reason of drug-resistant mutations and adverse effects of nucleoside analogs. In this study, two series of 2-arylthio-5-iodo pyrimidine analogs were firstly reported as potential anti-HBV agents.
  
  
  
  Target compounds were prepared according to two high-yielded synthetic routes, and their anti-HBV activities were evaluated on Hep2.2.15 and HepAD38 cell lines, respectively. To probe the mechanism of active agents, a cell-based (Huh-7) study of biochemical markers (e.g., HBeAg, HBsAg, intracellular HBV DNA and pgRNA) was performed. Furthermore, the pharmacophore models were constructed for future optimization of lead compounds.
  
  
  
  2-Arylthio-5-iodo pyrimidine derivatives firstly proved to be effective against HBV, which paves the way for future development of nonnucleoside anti-HBV agents.
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Fan
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University, Beijing 100191, China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Microbiology & Infectious Disease Center, School of Basic Medical Science, Peking University, Beijing 100191, China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.|State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D011743:Pyrimidines; D012367:RNA, Viral; D013440:Sulfides; C100808:pgRNA; D012313:RNA
keywords: DNA replication; HBV DNA polymerase; HBeAg; HBsAg; dose–response relationship; hepatitis B Virus; nonnucleoside inhibitors; pharmacophore models; pregenome RNA; pyrimidine derivatives