Novel hexahydropyrrolo[3,4-c]pyrrole CCR5 antagonists

Bioorg Med Chem Lett. 2010 May 15;20(10):3116-9. doi: 10.1016/j.bmcl.2010.03.095. Epub 2010 Mar 30.

Abstract

Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacokinetics
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology
  • CCR5 Receptor Antagonists*
  • HIV Fusion Inhibitors / chemical synthesis
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / pharmacokinetics
  • Humans
  • Microsomes, Liver / metabolism
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacokinetics
  • Rats
  • Receptors, CCR5 / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Benzamides
  • CCR5 Receptor Antagonists
  • HIV Fusion Inhibitors
  • Pyrroles
  • Receptors, CCR5