Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors

Chunlin Zhao; Christian Tovar; Xuefeng Yin; Qui Xu; Ivan T Todorov; Lyubomir T Vassilev; Li Chen

doi:10.1016/j.bmcl.2008.11.093

Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors

Bioorg Med Chem Lett. 2009 Jan 15;19(2):319-23. doi: 10.1016/j.bmcl.2008.11.093. Epub 2008 Nov 27.

Authors

Chunlin Zhao¹, Christian Tovar, Xuefeng Yin, Qui Xu, Ivan T Todorov, Lyubomir T Vassilev, Li Chen

Affiliation

¹ Discovery Chemistry, Research Center, Roche, Nutley, NJ 07110, USA. chunlin.zhao@roche.com

PMID: 19071019
DOI: 10.1016/j.bmcl.2008.11.093

Abstract

Cdc7 kinase plays a critical role in the regulation of DNA replication in eukaryotic cells and has been proposed as a target for cancer therapy. We have identified a class of Cdc7/Dbf4 inhibitors with a pyrido-thieno-pyrimidine core structure. Synthesis of a focused pyrido-thieno-pyrimidine library yielded potent and selective Cdc7 inhibitors with antiproliferative activity against cancer cells in vitro. Their synthesis and SAR data are presented herein.

MeSH terms

Cell Cycle Proteins / antagonists & inhibitors*
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Cell Cycle Proteins
Protein Kinase Inhibitors
Pyrimidines
CDC7 protein, human
Protein Serine-Threonine Kinases