Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

David R Anderson; Shridhar Hegde; Emily Reinhard; Leslie Gomez; William F Vernier; Len Lee; Shuang Liu; Aruna Sambandam; Patricia A Snider; Liaqat Masih

doi:10.1016/j.bmcl.2005.01.067

Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

Bioorg Med Chem Lett. 2005 Mar 15;15(6):1587-90. doi: 10.1016/j.bmcl.2005.01.067.

Authors

David R Anderson¹, Shridhar Hegde, Emily Reinhard, Leslie Gomez, William F Vernier, Len Lee, Shuang Liu, Aruna Sambandam, Patricia A Snider, Liaqat Masih

Affiliation

¹ Pfizer Global Research and Development, 700 Chesterfield Parkway W, Chesterfield, MO 63017, USA. david.r.anderson@pfizer.com

PMID: 15745802
DOI: 10.1016/j.bmcl.2005.01.067

Abstract

A class of inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2) was discovered. These compounds have demonstrated activity against the enzyme with IC50 values as low as 130 nM and suppress the expression of TNFalpha in U937 cells. These represent the first small molecule inhibitors of MK-2 to be reported.

MeSH terms

Animals
Gene Expression
Humans
MAP Kinase Kinase 2 / antagonists & inhibitors*
Models, Chemical
Molecular Structure
Pyridines / chemistry*
Pyridines / pharmacology*
Rats
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / metabolism
U937 Cells

Substances

Pyridines
Tumor Necrosis Factor-alpha
MAP Kinase Kinase 2