Biphenyl amide p38 kinase inhibitors 2: Optimisation and SAR.
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.
Angell
Richard M
RM
GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Angell
Tony D
TD
Bamborough
Paul
P
Brown
David
D
Brown
Murray
M
Buckton
Jacky B
JB
Cockerill
Stuart G
SG
Edwards
Chris D
CD
Jones
Katherine L
KL
Longstaff
Tim
T
Smee
Penny A
PA
Smith
Kathryn J
KJ
Somers
Don O
DO
Walker
Ann L
AL
Willson
Malcolm
M
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000577:Amides; D001713:Biphenyl Compounds; D010069:Oxadiazoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases