title: Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist.
abstract: Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. michael.dwyer@spcorp.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dwyer
authors.forename: Younong
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianping
authors.initials: J
authors.lastname: Chao
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aki
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chao
authors.forename: Purakkattle
authors.initials: P
authors.lastname: Biju
authors.forename: Viyyoor
authors.initials: V
authors.lastname: Girijavallabhan
authors.forename: Diane
authors.initials: D
authors.lastname: Rindgen
authors.forename: Richard
authors.initials: R
authors.lastname: Bond
authors.forename: Rosemary
authors.initials: R
authors.lastname: Mayer-Ezel
authors.forename: James
authors.initials: J
authors.lastname: Jakway
authors.forename: R William
authors.initials: RW
authors.lastname: Hipkin
authors.forename: James
authors.initials: J
authors.lastname: Fossetta
authors.forename: Waldemar
authors.initials: W
authors.lastname: Gonsiorek
authors.forename: Hong
authors.initials: H
authors.lastname: Bian
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fan
authors.forename: Carol
authors.initials: C
authors.lastname: Terminelli
authors.forename: Jay
authors.initials: J
authors.lastname: Fine
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundell
authors.forename: J Robert
authors.initials: JR
authors.lastname: Merritt
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rokosz
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaiser
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Tara
authors.initials: T
authors.lastname: Stauffer
authors.forename: Lynne
authors.initials: L
authors.lastname: Ozgur
authors.forename: John
authors.initials: J
authors.lastname: Baldwin
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Taveras
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001682:Biological Availability; D003503:Cyclobutanes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D051381:Rats; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C516686:2-hydroxy-N,N-dimethyl-3-(2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-enylamino)benzamide; D001549:Benzamides; D003503:Cyclobutanes; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C037689:benzamide