2-(Alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones as inhibitors of wild-type and mutant HIV-1: enantioselectivity studies

J Med Chem. 2012 Apr 12;55(7):3558-62. doi: 10.1021/jm201308v. Epub 2012 Mar 26.

Abstract

The single enantiomers of two pyrimidine-based HIV-1 non-nucleoside reverse transcriptase inhibitors, 1 (MC1501) and 2 (MC2082), were tested in both cellular and enzyme assays. In general, the R forms were more potent than their S counterparts and racemates and (R)-2 was more efficient than (R)-1 and the reference compounds, with some exceptions. Interestingly, (R)-2 displayed a faster binding to K103N RT with respect to WT RT, while (R)-1 showed the opposite behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology
  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / pharmacology
  • Cell Line
  • Enzyme Assays
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / chemistry
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Kinetics
  • Models, Molecular
  • Mutation
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Benzene Derivatives
  • Pyrimidinones
  • HIV Reverse Transcriptase