title: Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor.
abstract: Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.
authors.affiliation: Chemistry Department, Pfizer Global R&D, 2800 Plymouth Rd., Ann Arbor, MI 48105, USA. jack.li@pfizer.com
authors.forename: Jie Jack
authors.initials: JJ
authors.lastname: Li
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Carson
authors.forename: Bharat K
authors.initials: BK
authors.lastname: Trivedi
authors.forename: Wen Song
authors.initials: WS
authors.lastname: Yue
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Glynn
authors.forename: Steven R
authors.initials: SR
authors.lastname: Miller
authors.forename: David T
authors.initials: DT
authors.lastname: Connor
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Roth
authors.forename: Jay R
authors.initials: JR
authors.lastname: Luly
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Low
authors.forename: David J
authors.initials: DJ
authors.lastname: Heilig
authors.forename: Weixing
authors.initials: W
authors.lastname: Yang
authors.forename: Shixin
authors.initials: S
authors.lastname: Qin
authors.forename: Stephen
authors.initials: S
authors.lastname: Hunt
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D003959:Diamines; D011810:Quinoxalines; D023062:Receptors, Interleukin-8A; D002118:Calcium