2,6-Di(arylamino)-3-fluoropyridine Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors

J Med Chem. 2016 Mar 10;59(5):1854-68. doi: 10.1021/acs.jmedchem.5b01336. Epub 2016 Feb 8.

Abstract

New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.

Publication types

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

MeSH terms

  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Fluorobenzenes / chemical synthesis
  • Fluorobenzenes / chemistry
  • Fluorobenzenes / pharmacology
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology*
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Anti-HIV Agents
  • Fluorobenzenes
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase