Synthesis of bi-/tricyclic azasugars fused thiazinan-4-one and their HIV-RT inhibitory activity

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3426-9. doi: 10.1016/j.bmcl.2014.05.079. Epub 2014 Jun 2.

Abstract

Novel bi-/tricyclic azasugars fused thiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. The aryl group (phenyl or pyridyl) in mercaptan acid had an important effect on the formation of the diastereomers of the tricyclic hybrids 12b-15b. The new bi/tricyclic azasugars 3a-8a, 4b, 6b, 8b and the known ones 2a, 2b were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that compounds 2a-b, 4a, 4b, 5a, and 6a could effectively inhibit RT activity. Among them, the tricyclic azasugar 5a was the best one with the IC50 value of 0.49 μM. Structure-activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was benefit for their anti-HIV RT activity.

Keywords: Anti-HIV RT activity; Bi-/tricyclic azasugar; Microwave radiation; Staudinger/aza-Wittig; Thiazinan-4-one.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Carbohydrates / chemistry
  • Carbohydrates / pharmacology*
  • Dose-Response Relationship, Drug
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • Models, Molecular
  • Molecular Structure
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thiazines / chemistry
  • Thiazines / pharmacology*

Substances

  • Aza Compounds
  • Carbohydrates
  • Reverse Transcriptase Inhibitors
  • Thiazines
  • HIV Reverse Transcriptase