title: Discovery of potent and orally bioavailable N,N'-diarylurea antagonists for the CXCR2 chemokine receptor.
abstract: A series of 3-substituted N,N'-diarylureas was prepared and the structure-activity relationship relative to CXCR2 receptor affinity as well as their pharmacokinetic properties were examined. In vitro microsomal metabolism studies indicated that the lower clearance rates of the 3-sulfonamido-substituted compounds were most likely due to the suppression of glucuronidation.
authors.affiliation: GlaxoSmithKline, PO Box 1539, King of Prussia, PA 19406-0939, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.forename: Brent W
authors.initials: BW
authors.lastname: McCleland
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Widdowson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Palovich
authors.forename: John D
authors.initials: JD
authors.lastname: Elliott
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goodman
authors.forename: Miriam
authors.initials: M
authors.lastname: Burman
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sarau
authors.forename: Keith W
authors.initials: KW
authors.lastname: Ward
authors.forename: Melanie
authors.initials: M
authors.lastname: Nord
authors.forename: Bonnie M
authors.initials: BM
authors.lastname: Orr
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gorycki
authors.forename: Jakob
authors.initials: J
authors.lastname: Busch-Petersen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023063:Receptors, Interleukin-8B; D013453:Sulfonylurea Compounds