title: Identification and structure-activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists.
abstract: The synthesis and biological evaluation of a series of 1-aryl-3-piperidin-4-yl-urea derivatives as small-molecule CXCR3 antagonists is described. SAR studies resulted in significant improvement of potency and physicochemical properties and established the key pharmacophore of the series, and led to the identification of 9t, which exhibits an IC50 of 16 nM in the GTPgammaS35 functional assay.
authors.affiliation: UCB, Inflammation Discovery, Granta Park, Great Abington, Cambridge CB21 6GS, UK.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Allen
authors.forename: Amanda
authors.initials: A
authors.lastname: Bolt
authors.forename: Gayle A
authors.initials: GA
authors.lastname: Chapman
authors.forename: Roland L
authors.initials: RL
authors.lastname: Knight
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Meissner
authors.forename: David A
authors.initials: DA
authors.lastname: Owen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Watson
mesh_terms: D000818:Animals; D016466:CHO Cells; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002633:Chemotaxis / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014162:Transfection; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C515188:Cxcr3 protein, mouse; D010880:Piperidines; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014508:Urea