Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency

David R Anderson; Marvin J Meyers; Ravi G Kurumbail; Nicole Caspers; Gennadiy I Poda; Scott A Long; Betsy S Pierce; Matthew W Mahoney; Robert J Mourey; Mihir D Parikh

doi:10.1016/j.bmcl.2009.02.017

Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4882-4. doi: 10.1016/j.bmcl.2009.02.017. Epub 2009 Feb 8.

Authors

David R Anderson¹, Marvin J Meyers, Ravi G Kurumbail, Nicole Caspers, Gennadiy I Poda, Scott A Long, Betsy S Pierce, Matthew W Mahoney, Robert J Mourey, Mihir D Parikh

Affiliation

¹ Pfizer Global Research and Development, St Louis Laboratories, Chesterfield, MO 63017, USA. david.r.anderson@pfizer.com

PMID: 19616942
DOI: 10.1016/j.bmcl.2009.02.017

Abstract

Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

MeSH terms

Binding Sites
Cell Line, Tumor
Crystallography, X-Ray
Cyclin-Dependent Kinase 2 / antagonists & inhibitors
Cyclin-Dependent Kinase 2 / metabolism
Drug Design
Humans
MAP Kinase Kinase 2 / antagonists & inhibitors*
MAP Kinase Kinase 2 / metabolism
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology

Substances

Protein Kinase Inhibitors
Thiophenes
benzothiophene
Cyclin-Dependent Kinase 2
MAP Kinase Kinase 2