Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside HIV-1 reverse transcriptase inhibitors

J Org Chem. 2001 Sep 7;66(18):5958-64. doi: 10.1021/jo0100291.

Abstract

The Sonogashira and Stille cross-coupling reactions have been employed in the synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both in solution and on a solid support. In contrast to previous syntheses of NNRTIs in the ADAM series, the present strategy allows the incorporation of differently substituted aromatic rings in a stereochemically defined fashion. The most potent of the new ADAMs inhibited the cytopathic effect of HIV-1RF in CEM-SS cell culture with an EC50 value of 20 nM.

Publication types

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

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Caproates / chemical synthesis
  • Caproates / pharmacology
  • Cell Line
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • Humans
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Stereoisomerism

Substances

  • Anti-HIV Agents
  • Caproates
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase