Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors

Bioorg Med Chem. 2015 Feb 15;23(4):735-41. doi: 10.1016/j.bmc.2014.12.059. Epub 2015 Jan 3.

Abstract

A series of novel β-diketo derivatives which combined the virtues of dihydroxypyrimidine carboxamide derived from the evolution of DKA and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase and anti-HIV-1 activity. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives appear little inhibition to HIV-1 integrase. In addition, the preliminary structure-activity relationship (SAR) of these new derivatives was rationalized by docking studies.

Keywords: HIV-1 integrase; Inhibitors; N-Methylpyrimidone; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Drug Design
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology*
  • Humans
  • Molecular Docking Simulation
  • Pyrimidinones / chemical synthesis
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • 3-methyl-4-pyrimidone
  • HIV Integrase Inhibitors
  • Pyrimidinones
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1