title: Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development.
abstract: The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA. kim.f.mcclure@pfizer.com
authors.forename: Kim F
authors.initials: KF
authors.lastname: McClure
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.forename: Amit S
authors.initials: AS
authors.lastname: Kalgutkar
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Gabel
authors.forename: Laurent
authors.initials: L
authors.lastname: Audoly
authors.forename: John T
authors.initials: JT
authors.lastname: Barberia
authors.forename: John F
authors.initials: JF
authors.lastname: Braganza
authors.forename: Demetrius
authors.initials: D
authors.lastname: Carter
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carty
authors.forename: Santo R
authors.initials: SR
authors.lastname: Cortina
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dombroski
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Donahue
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Elliott
authors.forename: Colleen P
authors.initials: CP
authors.lastname: Gibbons
authors.forename: Crystal K
authors.initials: CK
authors.lastname: Jordan
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kuperman
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Labasi
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Laliberte
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: McCoy
authors.forename: Brian M
authors.initials: BM
authors.lastname: Naiman
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Nelson
authors.forename: Hang T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Peese
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Sweeney
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Taylor
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Trebino
authors.forename: Yuriy A
authors.initials: YA
authors.lastname: Abramov
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Laird
authors.forename: Walter A
authors.initials: WA
authors.lastname: Volberg
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Justin
authors.initials: J
authors.lastname: Bach
authors.forename: Franco
authors.initials: F
authors.lastname: Lombardo
mesh_terms: D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010080:Oxazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D010080:Oxazoles; D011725:Pyridines; D014230:Triazoles; D048051:p38 Mitogen-Activated Protein Kinases