Abstract
The biphenyl amides are a novel series of p38 MAP kinase inhibitors. Structure-activity relationships of the series against p38alpha are discussed with reference to the X-ray crystal structure of an example. The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.
MeSH terms
-
Administration, Oral
-
Amides / chemistry
-
Amides / pharmacokinetics
-
Amides / pharmacology*
-
Animals
-
Arthritis, Experimental / drug therapy
-
Arthritis, Experimental / metabolism
-
Biphenyl Compounds / chemistry
-
Biphenyl Compounds / pharmacokinetics
-
Biphenyl Compounds / pharmacology*
-
Crystallography, X-Ray
-
Models, Molecular
-
Molecular Conformation
-
Oxadiazoles / chemistry
-
Oxadiazoles / pharmacokinetics
-
Oxadiazoles / pharmacology
-
Piperazines / chemistry
-
Piperazines / pharmacokinetics
-
Piperazines / pharmacology
-
Protein Binding
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacokinetics
-
Protein Kinase Inhibitors / pharmacology*
-
Rats
-
Structure-Activity Relationship
-
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
p38 Mitogen-Activated Protein Kinases / chemistry
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
Amides
-
Biphenyl Compounds
-
Oxadiazoles
-
Piperazines
-
Protein Kinase Inhibitors
-
p38 Mitogen-Activated Protein Kinases