Discovery of a new class of p38 kinase inhibitors.
The MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry effort and exhibit activity in the nanomolar range. Very steep structure-activity relationships are observed within this class.
Dumas
J
J
Department of Chemistry Research, Bayer Research Center, West Haven, CT 06516, USA. jacques.dumas.b@bayer.com
Sibley
R
R
Riedl
B
B
Monahan
M K
MK
Lee
W
W
Lowinger
T B
TB
Redman
A M
AM
Johnson
J S
JS
Kingery-Wood
J
J
Scott
W J
WJ
Smith
R A
RA
Bobko
M
M
Schoenleber
R
R
Ranges
G E
GE
Housley
T J
TJ
Bhargava
A
A
Wilhelm
S M
SM
Shrikhande
A
A
D018501:Antirheumatic Agents / Q000138:chemical synthesis / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry; D020128:Inhibitory Concentration 50; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010024:Osteoporosis / Q000188:drug therapy; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases
D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D006843:Hydrocarbons, Chlorinated; D010671:Phenylurea Compounds; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases