Scaffold hopping: exploration of acetanilide-containing uracil analogues as potential NNRTIs

Bioorg Med Chem. 2015 Mar 1;23(5):1069-81. doi: 10.1016/j.bmc.2015.01.002. Epub 2015 Jan 8.

Abstract

In order to identify novel nonnucleoside inhibitors of HIV-1 reverse transcriptase two series of amide-containing uracil derivatives were designed as hybrids of two scaffolds of previously reported inhibitors. Subsequent biological evaluation confirmed acetamide uracil derivatives 15a-k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds 15c and 15i was employed to provide insight on their inhibitory properties and direct future design efforts.

Keywords: Amide; HIV; Inhibitors; NNRTIs; Nonnucleoside reverse transcriptase; Uracil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / chemistry*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Drug Evaluation, Preclinical
  • Humans
  • Models, Molecular
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Uracil / analogs & derivatives*

Substances

  • Acetanilides
  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Uracil
  • acetanilide