Phenoxypyrimidine inhibitors of p38alpha kinase: synthesis and statistical evaluation of the p38 inhibitory potencies of a series of 1-(piperidin-4-yl)-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl) imidazoles.
As a continuation of our work with 1,4,5 substituted imidazole inhibitors of p38alpha, we report a series of 1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-phenoxy-4-pyrimidinyl) imidazoles related to 7. The compounds have IC50's for inhibition of p38alpha ranging from 6.0 to 650nM. Statistical analysis of the p38beta inhibitor potencies shows a correlation of IC50's with the electron donating strength of low molecular weight substituents.
Boehm
J C
JC
Department of Medicinal Chemistry , GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. jeffrey_c_boehm@sbphrd.com
Bower
M J
MJ
Gallagher
T F
TF
Kassis
S
S
Johnson
S R
SR
Adams
J L
JL
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D010636:Phenols; D011743:Pyrimidines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases