title: Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives.
abstract: The optimization of a series of 1-aryl-3-piperidinyl urea derivatives is described in which incorporation of tropenyl and homotropenyl moieties has led to significant improvements in activity and drug-like properties. Replacement of the central piperidine with an exo-tropanyl unit led to the identification of compound 15 which provides a combination of excellent potency against human and murine receptors, drug-like properties and pharmacokinetics, thus providing a valuable tool for the evaluation of CXCR3 antagonists in models of human disease.
authors.affiliation: UCB Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom. bob.watson@ucb-group.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Watson
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Allen
authors.forename: Helen L
authors.initials: HL
authors.lastname: Birch
authors.forename: Gayle A
authors.initials: GA
authors.lastname: Chapman
authors.forename: Frances C
authors.initials: FC
authors.lastname: Galvin
authors.forename: Louise A
authors.initials: LA
authors.lastname: Jopling
authors.forename: Roland L
authors.initials: RL
authors.lastname: Knight
authors.forename: Dorica
authors.initials: D
authors.lastname: Meier
authors.forename: Kathryn
authors.initials: K
authors.lastname: Oliver
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Meissner
authors.forename: David A
authors.initials: DA
authors.lastname: Owen
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Thomas
authors.forename: Neil
authors.initials: N
authors.lastname: Tremayne
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Williams
mesh_terms: D000818:Animals; D003516:Cycloparaffins / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C515187:CXCR3 protein, human; D003516:Cycloparaffins; D010880:Piperidines; D054367:Receptors, CXCR3; D014508:Urea