Abstract
The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates.
MeSH terms
-
Chemistry, Pharmaceutical
-
Drug Design
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Humans
-
Inhibitory Concentration 50
-
Kinetics
-
Models, Chemical
-
Oxazoles / chemistry*
-
Pyridines / chemistry*
-
Solubility
-
Structure-Activity Relationship
-
Triazoles / chemistry
-
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
p38 Mitogen-Activated Protein Kinases / chemistry*
Substances
-
Enzyme Inhibitors
-
Oxazoles
-
Pyridines
-
Triazoles
-
p38 Mitogen-Activated Protein Kinases