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.
Thoma
Gebhard
G
Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland. gebhard.thoma@novartis.com
Baenteli
Rolf
R
Lewis
Ian
I
Wagner
Trixie
T
Oberer
Lukas
L
Blum
Wolfgang
W
Glickman
Fraser
F
Streiff
Markus B
MB
Zerwes
Hans-Guenter
HG
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