Rational design of 2-pyrrolinones as inhibitors of HIV-1 integrase

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6724-7. doi: 10.1016/j.bmcl.2011.09.054. Epub 2011 Sep 20.

Abstract

HIV-1 integrase is an essential enzyme for viral replication and a validated target for the development of drugs against AIDS. With an aim to discover new potent inhibitors of HIV-1 integrase, we developed a pharmacophore model based on reported inhibitors embodying structural diversity. Eight compounds of 2-pyrrolinones fitting all the features of the pharmacophore query were found through the screening of an in-house database. These candidates were successfully synthesized, and three of them showed strand transfer inhibitory activity, in which, one compound showed antiviral activity. Further mapping analysis and docking studies affirmed these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • HIV Infections / drug therapy
  • HIV Integrase / metabolism*
  • HIV Integrase Inhibitors / chemical synthesis
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Models, Molecular
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry*
  • Pyrrolidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • HIV Integrase Inhibitors
  • Pyrrolidinones
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1