title: CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase activity in whole blood.
abstract: A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but suffered from high plasma protein binding resulting in a >100 fold shift in activity in a functional GTPγS assay run in tandem in the presence and absence of human serum albumin. Introduction of an aryl amide with ethylenediamine linker led to compounds with reduced shifts and improved activity in whole blood.
authors: Pattern Recognition Receptors DPU, ImmunoInflammation Therapeutic Area Unit, GlaxoSmithKline, 1250 South Collegeville Road, PA 19426, USA.
authors: Gren Z
authors: GZ
authors: Wang
authors: Pamela A
authors: PA
authors: Haile
authors: Tom
authors: T
authors: Daniel
authors: Benjamin
authors: B
authors: Belot
authors: Andrew Q
authors: AQ
authors: Viet
authors: Krista B
authors: KB
authors: Goodman
authors: Deyou
authors: D
authors: Sha
authors: Sarah E
authors: SE
authors: Dowdell
authors: Norbert
authors: N
authors: Varga
authors: Xuan
authors: X
authors: Hong
authors: Subhas
authors: S
authors: Chakravorty
authors: Christine
authors: C
authors: Webb
authors: Carla
authors: C
authors: Cornejo
authors: Alan
authors: A
authors: Olzinski
authors: Roberta
authors: R
authors: Bernard
authors: Christopher
authors: C
authors: Evans
authors: Amanda
authors: A
authors: Emmons
authors: Jacques
authors: J
authors: Briand
authors: Chun-Wa
authors: CW
authors: Chung
authors: Ruben
authors: R
authors: Quek
authors: Dennis
authors: D
authors: Lee
authors: Peter J
authors: PJ
authors: Gough
authors: Clark A
authors: CA
authors: Sehon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D055879:Gene Knock-In Techniques; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000097:blood; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D054390:Receptors, CCR2; D012709:Serum Albumin; D013449:Sulfonamides; D016244:Guanosine 5'-O-(3-Thiotriphosphate)