1,3,4 Trisubstituted pyrrolidine CCR5 receptor antagonists bearing 4-aminoheterocycle substituted piperidine side chains

Bioorg Med Chem Lett. 2003 Feb 10;13(3):427-31. doi: 10.1016/s0960-894x(02)00988-5.

Abstract

A new class of 4-(aminoheterocycle)piperidine derived 1,3,4 trisubstituted pyrrolidine CCR5 antagonists is reported. Compound 4a is shown to have good binding affinity (1.8 nM) and antiviral activity in PBMC's (IC(95)=50 nM). Compound 4a also has improved PK properties relative to 1.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemical synthesis
  • CCR5 Receptor Antagonists*
  • CHO Cells
  • Chemokine CCL4
  • Cricetinae
  • Half-Life
  • HeLa Cells
  • Humans
  • Hydrogen Bonding
  • Macrophage Inflammatory Proteins / metabolism
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology*
  • Rats

Substances

  • Anti-HIV Agents
  • CCR5 Receptor Antagonists
  • Chemokine CCL4
  • Macrophage Inflammatory Proteins
  • Piperidines
  • Pyrrolidines