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

Gebhard Thoma; Rolf Baenteli; Ian Lewis; Trixie Wagner; Lukas Oberer; Wolfgang Blum; Fraser Glickman; Markus B Streiff; Hans-Guenter Zerwes

doi:10.1016/j.bmcl.2009.09.002

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.

Authors

Gebhard Thoma¹, Rolf Baenteli, Ian Lewis, Trixie Wagner, Lukas Oberer, Wolfgang Blum, Fraser Glickman, Markus B Streiff, Hans-Guenter Zerwes

Affiliation

¹ Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland. gebhard.thoma@novartis.com

PMID: 19783143
DOI: 10.1016/j.bmcl.2009.09.002

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