III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold

Bioorg Med Chem Lett. 2011 Dec 1;21(23):6982-6. doi: 10.1016/j.bmcl.2011.09.120. Epub 2011 Oct 5.

Abstract

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.

MeSH terms

  • Animals
  • Inhibitory Concentration 50
  • Molecular Structure
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Protein Binding / drug effects
  • Pyrazines / chemistry*
  • Pyrazines / pharmacology
  • Rats
  • Receptors, CXCR3 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Pyrazines
  • Receptors, CXCR3