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. Epub 2018 Jun 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Azoles / chemistry
  • Azoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design
  • HIV / drug effects*
  • HIV Protease Inhibitors / chemical synthesis
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • Manganese Compounds / chemistry
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Oxidation-Reduction
  • Oxides / chemistry
  • Ritonavir / chemical synthesis
  • Ritonavir / chemistry
  • Ritonavir / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Azoles
  • HIV Protease Inhibitors
  • Manganese Compounds
  • Organoselenium Compounds
  • Oxides
  • manganese oxide
  • Ritonavir