Design and synthesis of novel β-diketo derivatives as HIV-1 integrase inhibitors

Bioorg Med Chem. 2012 Jan 1;20(1):177-82. doi: 10.1016/j.bmc.2011.11.014. Epub 2011 Nov 22.

Abstract

A series of novel β-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole 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. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design*
  • Enzyme Activation / drug effects
  • HIV Integrase / chemistry*
  • HIV Integrase / metabolism
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • Humans
  • Keto Acids / chemical synthesis
  • Keto Acids / chemistry*
  • Keto Acids / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemistry

Substances

  • HIV Integrase Inhibitors
  • Keto Acids
  • Triazoles
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1