Special ergolines are highly selective, potent antagonists of the chemokine receptor CXCR3: discovery, characterization and preliminary SAR of a promising lead.
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.
Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland. gebhard.thoma@novartis.com
Gebhard
G
Thoma
Rolf
R
Baenteli
Ian
I
Lewis
Trixie
T
Wagner
Lukas
L
Oberer
Wolfgang
W
Blum
Fraser
F
Glickman
Markus B
MB
Streiff
Hans-Guenter
HG
Zerwes
D000818:Animals; D004285:Dogs; D055808:Drug Discovery; D004873:Ergolines / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D051381:Rats; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004873:Ergolines; D054367:Receptors, CXCR3