title: Inhibitors of unactivated p38 MAP kinase.
abstract: Inhibition of the p38 map kinase pathway has been shown to be beneficial in the treatment of inflammatory diseases. The first class of potent p38 kinase inhibitors was the pyridinylimidazole compounds from SKB. Since then several pyridinylimidazole-based compounds have been shown to inhibit activated p38 kinase in vitro and in vivo. We have developed a novel series of pyridinylimidazole-based compounds, which potently inhibit the p38 pathway by binding to unactivated p38 kinase and only weakly inhibiting activated p38 kinase activity in vitro.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202, Raritan, NJ 08869, USA. jbullington@ruxtonrx.com <jbullington@ruxtonrx.com>
authors.forename: James
authors.initials: J
authors.lastname: Bullington
authors.forename: Dennis
authors.initials: D
authors.lastname: Argentieri
authors.forename: Kristin
authors.initials: K
authors.lastname: Averill
authors.forename: Demetrius
authors.initials: D
authors.lastname: Carter
authors.forename: Druie
authors.initials: D
authors.lastname: Cavender
authors.forename: Bohumila
authors.initials: B
authors.lastname: Fahmy
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fan
authors.forename: Daniel
authors.initials: D
authors.lastname: Hall
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Heintzelman
authors.forename: Paul
authors.initials: P
authors.lastname: Jackson
authors.forename: Wai-Ping
authors.initials: WP
authors.lastname: Leung
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Ling
authors.forename: Gilbert
authors.initials: G
authors.lastname: Olini
authors.forename: Thomas
authors.initials: T
authors.lastname: Razler
authors.forename: Michael
authors.initials: M
authors.lastname: Reuman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rupert
authors.forename: Ronald
authors.initials: R
authors.lastname: Russell
authors.forename: John
authors.initials: J
authors.lastname: Siekierka
authors.forename: Scott
authors.initials: S
authors.lastname: Wadsworth
authors.forename: Russell
authors.initials: R
authors.lastname: Wolff
authors.forename: Bangping
authors.initials: B
authors.lastname: Xiang
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004952:Esters / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D004952:Esters; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; D000077489:Piperazine; D048051:p38 Mitogen-Activated Protein Kinases