Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases

Les A Dakin; Michael H Block; Huawei Chen; Erin Code; James E Dowling; Xiaomei Feng; Andrew D Ferguson; Isabelle Green; Alexander W Hird; Tina Howard; Erika K Keeton; Michelle L Lamb; Paul D Lyne; Hannah Pollard; Jon Read; Allan J Wu; Tao Zhang; Xiaolan Zheng

doi:10.1016/j.bmcl.2012.05.098

Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604. doi: 10.1016/j.bmcl.2012.05.098. Epub 2012 Jun 6.

Authors

Les A Dakin¹, Michael H Block, Huawei Chen, Erin Code, James E Dowling, Xiaomei Feng, Andrew D Ferguson, Isabelle Green, Alexander W Hird, Tina Howard, Erika K Keeton, Michelle L Lamb, Paul D Lyne, Hannah Pollard, Jon Read, Allan J Wu, Tao Zhang, Xiaolan Zheng

Affiliation

¹ Oncology iMed Sciences Group, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA.

PMID: 22727640
DOI: 10.1016/j.bmcl.2012.05.098

Abstract

Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data.

MeSH terms

Animals
Benzylidene Compounds / chemistry*
Benzylidene Compounds / pharmacology
Cell Line
Cell Proliferation / drug effects
Drug Discovery
Humans
Models, Molecular
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Proto-Oncogene Proteins / antagonists & inhibitors*
Rats
Structure-Activity Relationship
Thiazolidinediones / chemistry*
Thiazolidinediones / pharmacology

Substances

Benzylidene Compounds
Protein Kinase Inhibitors
Proto-Oncogene Proteins
Thiazolidinediones
Protein Serine-Threonine Kinases