Solid phase synthesis of novel pyrrolidinedione analogs as potent HIV-1 integrase inhibitors

J Comb Chem. 2010 Jan-Feb;12(1):84-90. doi: 10.1021/cc9001026.

Abstract

A novel series of HIV-1 integrase inhibitors were identified from a 100 member (4R(1) x 5R(2) x 5R(3)) library of pyrrolidinedione amides. A solid-phase route was developed which facilitates the simultaneous variation at R(1), R(2), and R(3) of the pyrrolidinedione scaffold. The resulting library samples were assayed for HIV-1 integrase activity and analyzed to determine the R(1), R(2), and R(3) reagent contributions towards the activity.

MeSH terms

  • Combinatorial Chemistry Techniques / methods
  • Drug Design*
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Succinimides / chemical synthesis*
  • Succinimides / chemistry
  • Succinimides / pharmacology

Substances

  • HIV Integrase Inhibitors
  • Succinimides