Synthesis and antiviral activity of aryl phosphoramidate derivatives of beta-D- and beta-L-C-5-substituted 2',3'-didehydro-2',3'-dideoxy-uridine bearing linker arms

J Enzyme Inhib Med Chem. 2005 Dec;20(6):533-49. doi: 10.1080/14756360500220343.

Abstract

We have previously reported the synthesis and evaluation of potent anti-human immunodeficiency virus compounds based on beta-D-d4T analogues bearing a tether attached at the C-5 position and their beta-L-counterparts. Initial study revealed a requirement for an alkyl side-chain with an optimal length of 12 carbons for a weak antiviral activity. As a continuation of that work, we have now prepared the corresponding phosphoramidate derivatives as possible membrane-permeable prodrugs. Phosphorochloridate chemistry gave the target phosphoramidates which were tested for anti-human immunodeficiency virus type 1 activity; unfortunately, they were devoid of anti-HIV activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dideoxynucleosides / chemistry*
  • Drug Evaluation, Preclinical
  • HIV-1 / drug effects
  • Humans
  • Molecular Structure
  • Phosphoric Acids / chemistry*
  • Structure-Activity Relationship
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / chemistry

Substances

  • Amides
  • Anti-HIV Agents
  • Dideoxynucleosides
  • Phosphoric Acids
  • phosphoramidic acid
  • Uridine Monophosphate