Development of CXCR3 antagonists. Part 4: discovery of 2-amino-(4-tropinyl)quinolines.
The synthesis and biological evaluation of a novel series of 2-aminoquinoline substituted piperidines and tropanes incorporating a homotropene moiety is herein described. The series exhibits potent antagonism of the CXCR3 receptor and superior physicochemical properties. Compound 24d was found to be orally bioavailable, and PK/PD studies suggested it as a suitable tool for studying the role of CXCR3 in models of disease.
Knight
Roland L
RL
UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom. roland.knight@ucb-group.com
Allen
Daniel R
DR
Birch
Helen L
HL
Chapman
Gayle A
GA
Galvin
Frances C
FC
Jopling
Louise A
LA
Lock
Christopher J
CJ
Meissner
Johannes W G
JW
Owen
David A
DA
Raphy
Gilles
G
Watson
Robert J
RJ
Williams
Sophie C
SC
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*
C515188:Cxcr3 protein, mouse; D011804:Quinolines; D054367:Receptors, CXCR3