1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: modifications of the arylpropylpiperidine side chains

Bioorg Med Chem Lett. 2003 Jan 6;13(1):119-23. doi: 10.1016/s0960-894x(02)00829-6.

Abstract

The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology
  • CCR5 Receptor Antagonists*
  • Dogs
  • Half-Life
  • Humans
  • Leukocytes, Mononuclear
  • Macaca mulatta
  • Metabolic Clearance Rate
  • Piperidines / chemistry
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / pharmacokinetics*
  • Pyrrolidines / pharmacology
  • Radioligand Assay
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Piperidines
  • Pyrrolidines
  • piperidine