Inhibitors of unactivated p38 MAP kinase.
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.
Bullington
James
J
Johnson and Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202, Raritan, NJ 08869, USA. jbullington@ruxtonrx.com <jbullington@ruxtonrx.com>
Argentieri
Dennis
D
Averill
Kristin
K
Carter
Demetrius
D
Cavender
Druie
D
Fahmy
Bohumila
B
Fan
Xiaodong
X
Hall
Daniel
D
Heintzelman
Geoffrey
G
Jackson
Paul
P
Leung
Wai-Ping
WP
Li
Xun
X
Ling
Ping
P
Olini
Gilbert
G
Razler
Thomas
T
Reuman
Michael
M
Rupert
Kenneth
K
Russell
Ronald
R
Siekierka
John
J
Wadsworth
Scott
S
Wolff
Russell
R
Xiang
Bangping
B
Zhang
Yue-Mei
YM
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
D004791:Enzyme Inhibitors; D004952:Esters; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; D000077489:Piperazine; D048051:p38 Mitogen-Activated Protein Kinases