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

J C Boehm; M J Bower; T F Gallagher; S Kassis; S R Johnson; J L Adams

doi:10.1016/s0960-894x(01)00163-9

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

Bioorg Med Chem Lett. 2001 May 7;11(9):1123-6. doi: 10.1016/s0960-894x(01)00163-9.

Authors

J C Boehm¹, M J Bower, T F Gallagher, S Kassis, S R Johnson, J L Adams

Affiliation

¹ Department of Medicinal Chemistry , GlaxoSmithKline Pharmaceuticals, King of Prussia, PA 19406, USA. [email protected]

PMID: 11354358
DOI: 10.1016/s0960-894x(01)00163-9

Abstract

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.

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Models, Molecular
Phenols / chemical synthesis*
Phenols / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
p38 Mitogen-Activated Protein Kinases

Substances

Enzyme Inhibitors
Phenols
Pyrimidines
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases