title: Synthesis and structure-activity relationships of new disubstituted phenyl-containing 3,4-diamino-3-cyclobutene-1,2-diones as CXCR2 receptor antagonists.
abstract: A series of 3,4- and 3,5-disubstituted phenyl-containing cyclobutenedione analogues were synthesized and evaluated as CXCR2 receptor antagonists. Variations in the disubstitution pattern of the phenyl ring afforded new compounds with potent CXCR2 binding affinity in the low nanomolar ranges. Moreover, two potent compounds 19 and 26 exhibited good oral pharmacokinetic profiles.
authors.affiliation: Pharmacopeia, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. galai@pcop.com
authors.forename: Gaifa
authors.initials: G
authors.lastname: Lai
authors.forename: J Robert
authors.initials: JR
authors.lastname: Merritt
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: He
authors.forename: Daming
authors.initials: D
authors.lastname: Feng
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chao
authors.forename: Michael F
authors.initials: MF
authors.lastname: Czarniecki
authors.forename: Laura L
authors.initials: LL
authors.lastname: Rokosz
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stauffer
authors.forename: Diane
authors.initials: D
authors.lastname: Rindgen
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Taveras
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000882:Haplorhini; D015394:Molecular Structure; D011485:Protein Binding; D051381:Rats; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D003503:Cyclobutanes; D023063:Receptors, Interleukin-8B