Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular 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

doi:10.1016/j.bmcl.2009.02.015

Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4878-81. doi: 10.1016/j.bmcl.2009.02.015. 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

Affiliation

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

PMID: 19616945
DOI: 10.1016/j.bmcl.2009.02.015

Abstract

Identification of potent benzothiophene inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2), structure-activity relationship (SAR) studies, selectivity assessments against CDK2, cellular potency and mechanism of action are presented. Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors.

MeSH terms

Binding Sites
Cell Line, Tumor
Crystallography, X-Ray
Cyclin-Dependent Kinase 2 / antagonists & inhibitors
Cyclin-Dependent Kinase 2 / metabolism
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
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology

Substances

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