title: Development of CXCR3 antagonists. Part 4: discovery of 2-amino-(4-tropinyl)quinolines.
abstract: 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.
authors: UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom. roland.knight@ucb-group.com
authors: Roland L
authors: RL
authors: Knight
authors: Daniel R
authors: DR
authors: Allen
authors: Helen L
authors: HL
authors: Birch
authors: Gayle A
authors: GA
authors: Chapman
authors: Frances C
authors: FC
authors: Galvin
authors: Louise A
authors: LA
authors: Jopling
authors: Christopher J
authors: CJ
authors: Lock
authors: Johannes W G
authors: JW
authors: Meissner
authors: David A
authors: DA
authors: Owen
authors: Gilles
authors: G
authors: Raphy
authors: Robert J
authors: RJ
authors: Watson
authors: Sophie C
authors: SC
authors: Williams
mesh_terms: 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*
chemical_list: C515188:Cxcr3 protein, mouse; D011804:Quinolines; D054367:Receptors, CXCR3