Acyclic analogues of 3'-azido-3'-deoxythymidine as potential antiviral agents. Nucleoside synthesis by Michael addition

J Med Chem. 1989 Jan;32(1):73-6. doi: 10.1021/jm00121a015.

Abstract

An acyclic derivative of 3'-azido-3'-deoxythymidine, (R,S)-1-[1-(2-hydroxyethoxy)-3-azidopropyl]thymine (2), has been synthesized by a path involving Michael-type addition. Related thymidine analogues lacking the C(3')-C(4') bond were similarly obtained. The method provides a versatile new route to nucleoside analogues. The new compounds were found to be essentially inactive against human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro when tested up to 100 microM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Chlorocebus aethiops
  • HIV-1 / drug effects
  • HIV-2 / drug effects
  • Humans
  • Structure-Activity Relationship
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / pharmacology

Substances

  • Antiviral Agents
  • 1-(1-(2-hydroxyethoxy)-3-azidopropyl)thymine
  • Zidovudine