title: Nicotinamide N-oxides as CXCR2 antagonists.
abstract: A series of nicotinamide N-oxides was synthesized and shown to be novel, potent, and selective antagonists of the CXCR2 receptor. Furthermore, these compounds showed significant functional activity against GRO-alpha-driven human neutrophil chemotaxis. Compounds of this class may be useful for the treatment of inflammatory, auto-immune, and allergic disorders.
authors.affiliation: Department of Chemistry, Celltech R&D, Inc., 1631 220th Street SE, 98021, Bothell, WA, USA. neil.cutshall@celltechgroup.com
authors.forename: N S
authors.initials: NS
authors.lastname: Cutshall
authors.forename: R
authors.initials: R
authors.lastname: Ursino
authors.forename: K A
authors.initials: KA
authors.lastname: Kucera
authors.forename: J
authors.initials: J
authors.lastname: Latham
authors.forename: N C
authors.initials: NC
authors.lastname: Ihle
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy; D001665:Binding Sites / Q000502:physiology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B; D009536:Niacinamide; C037645:nicotinamide N-oxide