title: Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor.
abstract: Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent antihyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res.1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain2006, 10, 537].
authors.affiliation: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Beswick
authors.forename: Andy
authors.initials: A
authors.lastname: Billinton
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Chambers
authors.forename: David K
authors.initials: DK
authors.lastname: Dean
authors.forename: Elena
authors.initials: E
authors.lastname: Fonfria
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gleave
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Medhurst
authors.forename: Anton D
authors.initials: AD
authors.lastname: Michel
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Moses
authors.forename: Sadhana
authors.initials: S
authors.lastname: Patel
authors.forename: Shilina A
authors.initials: SA
authors.lastname: Roman
authors.forename: Sue
authors.initials: S
authors.lastname: Roomans
authors.forename: Stefan
authors.initials: S
authors.lastname: Senger
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Daryl S
authors.initials: DS
authors.lastname: Walter
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D010146:Pain / Q000188:drug therapy; D058920:Purinergic P2X Receptor Antagonists; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D058920:Purinergic P2X Receptor Antagonists; D011720:Pyrazoles; D058486:Receptors, Purinergic P2X7