title: Synthesis and structure-activity relationships of 3,4-diaminocyclobut-3-ene-1,2-dione CXCR2 antagonists.
abstract: A novel series of 3,4-diaminocyclobut-3-ene-1,2-diones was prepared and found to show potent inhibitory activity of CXCR2 binding and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Microsome stability and Caco2 studies were subsequently used to show that compounds of this chemotype are predicted to have good oral bioavailability and are thus suitable for pharmaceutical development.
authors.affiliation: Pharmacopeia Drug Discovery, Inc., 3000 Eastpark Blvd., Cranbury, NJ 08512, USA. bmerritt@pcop.com
authors.forename: J Robert
authors.initials: JR
authors.lastname: Merritt
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rokosz
authors.forename: Kingsley H
authors.initials: KH
authors.lastname: Nelson
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaiser
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stauffer
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Ozgur
authors.forename: Adriane
authors.initials: A
authors.lastname: Schilling
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: John J
authors.initials: JJ
authors.lastname: Baldwin
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Taveras
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dwyer
authors.forename: Jianping
authors.initials: J
authors.lastname: Chao
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D018938:Caco-2 Cells; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D003503:Cyclobutanes; D023063:Receptors, Interleukin-8B