Special ergolines are highly selective, potent antagonists of the chemokine receptor CXCR3: discovery, characterization and preliminary SAR of a promising lead

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6185-8. doi: 10.1016/j.bmcl.2009.09.002. Epub 2009 Sep 6.

Abstract

The special ergoline 1 is a highly potent, selective antagonist of the chemokine receptor CXCR3. The surprising selectivity of this LSD-related compound can be explained by different electronic and steric properties of the ergoline core structure caused by the urea portion of the molecule. Discovery, biopharmaceutical properties and first derivatives of this promising lead compound are discussed.

MeSH terms

  • Animals
  • Dogs
  • Drug Discovery
  • Ergolines / chemistry*
  • Ergolines / pharmacology
  • Humans
  • Mice
  • Microsomes, Liver / metabolism
  • Molecular Conformation
  • Rats
  • Receptors, CXCR3 / antagonists & inhibitors*
  • Receptors, CXCR3 / metabolism
  • Structure-Activity Relationship

Substances

  • Ergolines
  • Receptors, CXCR3