title: Benzimidazolone p38 inhibitors.
abstract: The synthesis and in vitro p38 alpha activity of a novel series of benzimidazolone inhibitors is described. The p38 alpha SAR is consistent with a mode of binding wherein the benzimidazolone carbonyl serves as the H-bond acceptor to Met109 of p38 alpha in a manner analogous to the pyridine nitrogen of prototypical pyridylimidazole p38 inhibitors. Potent p38 alpha activity comparable to that of several previously reported p38 inhibitors is observed for this novel chemotype.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dombroski
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.forename: Kim F
authors.initials: KF
authors.lastname: McClure
authors.forename: John T
authors.initials: JT
authors.lastname: Barberia
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carty
authors.forename: Santo R
authors.initials: SR
authors.lastname: Cortina
authors.forename: Csilla
authors.initials: C
authors.lastname: Csiki
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Dipesa
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Elliott
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Gabel
authors.forename: Crystal K
authors.initials: CK
authors.lastname: Jordan
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Labasi
authors.forename: William H
authors.initials: WH
authors.lastname: Martin
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Peese
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Stock
authors.forename: Linne
authors.initials: L
authors.lastname: Svensson
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Sweeney
authors.forename: Chul H
authors.initials: CH
authors.lastname: Yu
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D011725:Pyridines / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; C490855:L-790070; D011725:Pyridines; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases