Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and HIV-1 Integrase Inhibitory Activities of 4-Hydroxy-5-azacoumarin 3-Carboxamides

  • Lee, Seung-Uk (Life Sciences Research Division, Korea Institute of Science & Technology) ;
  • Park, Jang-Hyun (Life Sciences Research Division, Korea Institute of Science & Technology) ;
  • Kwon, Tae-Hoon (Kyung Hee East-West Pharmaceutical Research Institute and Department of Pharmaceutical Sciences & Department of Life and Nanopharmaceutical Science, Kyung Hee University) ;
  • Yoo, Yeong-Jae (Life Sciences Research Division, Korea Institute of Science & Technology) ;
  • Lee, Jae-Yeol (Research Institute of Basic Science and Department of Chemistry Sciences & Department of Life and Nanopharmaceutical Science, Kyung Hee University) ;
  • Shin, Cha-Gyun (Department of Biotechnology, Chung-Ang University) ;
  • Yoo, Kyung-Ho (Life Sciences Research Division, Korea Institute of Science & Technology) ;
  • Lee, Yong-Sup (Kyung Hee East-West Pharmaceutical Research Institute and Department of Pharmaceutical Sciences & Department of Life and Nanopharmaceutical Science, Kyung Hee University)
  • Published : 2007.09.20
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Abstract

Recently, it has been reported that the inhibition of the strand transfer function of HIV-1 integrase is necessary to obtain significant antiviral activity. Accordingly, several compounds typified by aryl 1,3-diketo acids that can inhibit strand transfer reaction of HIV-1 IN have been identified. In this work, we synthesized new 4- hydroxy-5-azacoumarin-3-carbox(thio)amides (1a-h) and evaluated for the inhibition of HIV-1 IN strand transfer reaction with a brief SAR. Among synthesized, compound 1e was the most potent HIV-1 IN inhibitor with equipotent activity to that of L-708,906. Therefore, the 4-hydroxy-5-azacoumarin ring can be considered as a new scaffold in designing more potent of HIV-1 IN inhibitors for treatment of AIDS.

Keywords

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