RNase H active site inhibitors of human immunodeficiency virus type 1 reverse transcriptase: design, biochemical activity, and structural information

J Med Chem. 2009 Oct 8;52(19):5781-4. doi: 10.1021/jm900597q.


Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding was demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.

MeSH terms

  • Carboxylic Acids
  • Catalytic Domain
  • Drug Design
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Humans
  • Protein Binding
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Ribonuclease H / antagonists & inhibitors*


  • Carboxylic Acids
  • Pyrimidines
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Ribonuclease H

Associated data

  • PDB/3HYF