Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: synthesis, biological evaluation, and structure-activity relationships

Takao Horiuchi; Jun Chiba; Kouichi Uoto; Tsunehiko Soga

doi:10.1016/j.bmcl.2008.11.090

Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: synthesis, biological evaluation, and structure-activity relationships

Bioorg Med Chem Lett. 2009 Jan 15;19(2):305-8. doi: 10.1016/j.bmcl.2008.11.090. Epub 2008 Nov 27.

Authors

Takao Horiuchi¹, Jun Chiba, Kouichi Uoto, Tsunehiko Soga

Affiliation

¹ Medicinal Chemistry Research Laboratory II, Daiichi Sankyo Co. Ltd., 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan. [email protected]

PMID: 19091560
DOI: 10.1016/j.bmcl.2008.11.090

Abstract

The synthesis and evaluation of new analogues of thieno[2,3-d]pyrimidin-4-yl hydrazones are described. 2-Pyrdinecarboxaldehyde [6-(tert-butyl)thieno[2,3-d]pyrimidine-4-yl]hydrazone derivatives have been identified as cyclin-dependent kinase 4 (CDK4) inhibitors. The potency, selectivity profile, and structure-activity relationship of this series of compounds are discussed.

MeSH terms

Cell Line, Tumor
Cyclin D1 / antagonists & inhibitors*
Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
Drug Screening Assays, Antitumor
Humans
Hydrazones / chemical synthesis*
Hydrazones / chemistry
Hydrazones / pharmacology*
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Hydrazones
Protein Kinase Inhibitors
Pyrimidines
Cyclin D1
Cyclin-Dependent Kinase 4