Discovery and Synthesis of Heterocyclic Carboxamide Derivatives as Potent Anti-norovirus Agents

DOI Web Site Web Site PubMed 被引用文献1件 参考文献15件 オープンアクセス
  • Ohba Mai
    Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene
  • Oka Tomoichiro
    Department of Virology II, National Institute of Infectious Diseases
  • Ando Takayuki
    Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene
  • Arahata Saori
    Department of Microbiology, Shizuoka Institute of Environment and Hygiene
  • Ikegaya Asaka
    Department of Microbiology, Shizuoka Institute of Environment and Hygiene
  • Takagi Hirotaka
    Division of Biological Safety Control and Research, National Institute of Infectious Diseases
  • Ogo Naohisa
    Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene
  • Owada Kazuhiro
    Department of Pharmaceutical and Food Science, Shizuoka Institute of Environment and Hygiene
  • Kawamori Fumihiko
    Department of Microbiology, Shizuoka Institute of Environment and Hygiene
  • Wang Qiuhong
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University
  • Saif Linda J.
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University
  • Asai Akira
    Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka

この論文をさがす

抄録

There is an urgent need for structurally novel anti-norovirus agents. In this study, we describe the synthesis, anti-norovirus activity, and structure–activity relationship (SAR) of a series of heterocyclic carboxamide derivatives. Heterocyclic carboxamide 1 (50% effective concentration (EC50)=37 µM) was identified by our screening campaign using the cytopathic effect reduction assay. Initial SAR studies suggested the importance of halogen substituents on the heterocyclic scaffold and identified 3,5-di-boromo-thiophene derivative 2j (EC50=24 µM) and 4,6-di-fluoro-benzothiazole derivative 3j (EC50=5.6 µM) as more potent inhibitors than 1. Moreover, their hybrid compound, 3,5-di-bromo-thiophen-4,6-di-fluoro-benzothiazole 4b, showed the most potent anti-norovirus activity with a EC50 value of 0.53 µM (70-fold more potent than 1). Further investigation suggested that 4b might inhibit intracellular viral replication or the late stage of viral infection.

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (15)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ