Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains

Bioorg Med Chem Lett. 2004 Feb 23;14(4):935-9. doi: 10.1016/j.bmcl.2003.12.004.


Replacement of the flexible connecting chains between the piperidine moiety and an aromatic group in previous CCR5 antagonists with heterocycles, such as pyrazole and isoxazole, provided potent CCR5 antagonists with excellent anti-HIV-1 activity in vitro. SAR studies revealed optimal placement of an unsubstituted nitrogen atom in the heterocycle to be meta to the bond connected to the 4-position of piperidine. Truncation of a benzyl group to a phenyl group afforded compounds with dramatically improved oral bioavailability, albeit with reduced activity.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacokinetics*
  • CCR5 Receptor Antagonists*
  • Cell Division / drug effects
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacokinetics*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Rats
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Piperidines
  • Pyrazoles