Design and synthesis of selenazole-substituted ritonavir analogs

  • Bioorg Med Chem Lett. 2018 Aug 1;28(14):2379-2381. doi: 10.1016/j.bmcl.2018.06.027.
Junfei Qiao  1 ,  Chuanfang Zhao  2 ,  Jun Liu  3 ,  Yuguo Du  4
Affiliations
  • 1. State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Beijing 100085, China; School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2. School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3. State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Beijing 100085, China.
  • 4. State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Science, Beijing 100085, China; School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID: 29934245 DOI: 10.1016/j.bmcl.2018.06.027
Abstract

With the help of Surflex-Dock calculation, two ritonavir analogs in which one thioazole unit was replaced by selenazole have been designed and synthesized. The key selenazole structure was constructed from β-azido diselenide through a cascade diselenide cleavage/selenocarbonylation/Staudinger reduction/aza-Wittig reaction and a following MnO2 oxidation. The accordingly prepared compounds exhibited good anti-HIV-1 (IIIB) activities comparable to that of the original ritonavir, as well as the positive SI values.

Keywords
Antiviral; One-pot reaction; Protease inhibitor; Ritonavir; Selenazole.