Imidazopyrimidines, potent inhibitors of p38 MAP kinase.
The MAP kinase p38 is implicated in the release of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. Inhibition of cytokine release may be a useful treatment for inflammatory conditions such as rheumatoid arthritis and Crohn's disease. A novel series of imidazopyrimidines have been discovered that potently inhibit p38 and suppress the production of TNF-alpha in vivo.
Rupert
Kenneth C
KC
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202, Raritan, NJ 08869, USA. krupert@prdus.jnj.com
Henry
James R
JR
Dodd
John H
JH
Wadsworth
Scott A
SA
Cavender
Druie E
DE
Olini
Gilbert C
GC
Fahmy
Bohumila
B
Siekierka
John J
JJ
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases