Aminopyrimidinone cdc7 kinase inhibitors

Keith W Woods; Chunqiu Lai; Julie M Miyashiro; Yunsong Tong; Alan S Florjancic; Edward K Han; Niru Soni; Yan Shi; Loren Lasko; Joel D Leverson; Eric F Johnson; Alexander R Shoemaker; Thomas D Penning

doi:10.1016/j.bmcl.2012.01.041

Aminopyrimidinone cdc7 kinase inhibitors

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1940-3. doi: 10.1016/j.bmcl.2012.01.041. Epub 2012 Jan 25.

Authors

Keith W Woods¹, Chunqiu Lai, Julie M Miyashiro, Yunsong Tong, Alan S Florjancic, Edward K Han, Niru Soni, Yan Shi, Loren Lasko, Joel D Leverson, Eric F Johnson, Alexander R Shoemaker, Thomas D Penning

Affiliation

¹ Abbott Laboratories, 100 Abbott Park Rd., R47S AP10/307, Abbott Park, IL 60064-6101, USA. [email protected]

PMID: 22326396
DOI: 10.1016/j.bmcl.2012.01.041

Abstract

We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (K(i)) less than 1nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.

MeSH terms

Amines / chemistry
Amines / pharmacology
Cell Cycle Proteins / antagonists & inhibitors*
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Humans
Minichromosome Maintenance Complex Component 2
Nuclear Proteins / metabolism
Phosphorylation / drug effects
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology*
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / metabolism
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*
Structure-Activity Relationship

Substances

Amines
Cell Cycle Proteins
Nuclear Proteins
Protein Kinase Inhibitors
Pyrimidinones
CDC7 protein, human
Protein Serine-Threonine Kinases
MCM2 protein, human
Minichromosome Maintenance Complex Component 2