A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(2H)-ones as potency inhibitors of HIV-1 variants

Org Biomol Chem. 2016 Jan 28;14(4):1413-20. doi: 10.1039/c5ob02154e. Epub 2015 Dec 16.

Abstract

3-Iodo-4-(2'-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-ones, as effective non-nucleoside reverse transcriptase inhibitors, were synthesized and resolved with different configurations. Biological results revealed that the trans-racemate 2b exhibited more potent activity than the cis-isomers. Noticeably, the trans-(S,S)-enantiomer 2e turned out to be significantly more potent than its counterpart enantiomer 2d against wild-type and double-mutant strains with high selectivity indexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Dose-Response Relationship, Drug
  • Genetic Variation / drug effects
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Pyridones / chemical synthesis
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-one
  • Pyridones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase