Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: identification and optimisation of substituted 2,4-bis anilino pyrimidines

Gloria A Breault; Rebecca P A Ellston; Stephen Green; S Russell James; Philip J Jewsbury; Catherine J Midgley; Richard A Pauptit; Claire A Minshull; Julie A Tucker; J Elizabeth Pease

doi:10.1016/s0960-894x(03)00203-8

Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: identification and optimisation of substituted 2,4-bis anilino pyrimidines

Bioorg Med Chem Lett. 2003 Sep 15;13(18):2961-6. doi: 10.1016/s0960-894x(03)00203-8.

Authors

Gloria A Breault¹, Rebecca P A Ellston, Stephen Green, S Russell James, Philip J Jewsbury, Catherine J Midgley, Richard A Pauptit, Claire A Minshull, Julie A Tucker, J Elizabeth Pease

Affiliation

¹ AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

PMID: 12941312
DOI: 10.1016/s0960-894x(03)00203-8

Abstract

Through chemical modification and X-ray crystallography we identified the 2,4-bis anilino pyrimidines as potent inhibitors of CDK4. Herein, we describe the optimisation of this series.

MeSH terms

Adenosine Triphosphate / chemistry
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Binding Sites
Crystallography, X-Ray
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Molecular Structure
Proto-Oncogene Proteins*
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Proto-Oncogene Proteins
Pyrimidines
Adenosine Triphosphate
CDK4 protein, human
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases