Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity.
The biphenyl amides (BPAs) are a novel series of p38alpha MAP kinase inhibitor. The optimisation of the series to give compounds that are potent in an in vivo disease model is discussed. SAR is presented and rationalised with reference to the crystallographic binding mode.
Angell
Richard
R
GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
Aston
Nicola M
NM
Bamborough
Paul
P
Buckton
Jacky B
JB
Cockerill
Stuart
S
deBoeck
Suzanne J
SJ
Edwards
Chris D
CD
Holmes
Duncan S
DS
Jones
Katherine L
KL
Laine
Dramane I
DI
Patel
Shila
S
Smee
Penny A
PA
Smith
Kathryn J
KJ
Somers
Don O
DO
Walker
Ann L
AL
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
D001549:Benzamides; D001713:Biphenyl Compounds; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14