Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV

Bioorg Med Chem. 2010 Apr 1;18(7):2370-4. doi: 10.1016/j.bmc.2010.03.007. Epub 2010 Mar 9.


A series of novel diarylpyrimidine analogues featuring a hydroxyiminomethyl group between the pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC(50) value ranging from 0.569microM to 0.005microM. 4-(4-((Hydroxyimino) (3-methoxyphenyl)methyl)pyrimidin-2-ylamino)benzonitrile (12n) was identified as the most active compound of this new series (EC(50)=0.025microM, SI >1223) associated with moderate activity against HIV-1 double mutant strains (K103N+Y181C) (EC(50)=8.72microM) in addition to its anti-HIV-2 activity with an EC(50) value of 8.31microM. Preliminary structure-activity relationship (SAR) among the newly synthesized DAPYs was also investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology*
  • Cell Line / drug effects
  • Cell Survival / drug effects
  • HIV-1 / drug effects*
  • HIV-1 / enzymology*
  • HIV-2 / drug effects
  • Humans
  • Indicators and Reagents
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • Indicators and Reagents
  • Pyrimidines
  • Reverse Transcriptase Inhibitors