II. SAR studies of pyridyl-piperazinyl-piperidine derivatives as CXCR3 chemokine antagonists

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1527-31. doi: 10.1016/j.bmcl.2010.12.114. Epub 2010 Dec 28.

Abstract

The structure-human CXCR3 binding affinity relationship of a series of pyridyl-piperazinyl-piperidine derivatives was explored. The optimization campaign highlighted the pronounced effect of 2'-piperazine substitution on CXCR3 receptor affinity. Analog 18j, harboring a 2'(S)-ethylpiperazine moiety, exhibited a human CXCR3 IC(50) of 0.2 nM.

MeSH terms

  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Piperazine
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Receptors, CXCR3 / agonists*
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Piperidines
  • Pyridines
  • Receptors, CXCR3
  • Piperazine
  • piperidine