Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2

Douglas S Williamson; Martin J Parratt; Justin F Bower; Jonathan D Moore; Christine M Richardson; Pawel Dokurno; Andrew D Cansfield; Geraint L Francis; Richard J Hebdon; Rob Howes; Philip S Jackson; Andrea M Lockie; James B Murray; Claire L Nunns; Jenifer Powles; Alan Robertson; Allan E Surgenor; Christopher J Torrance

doi:10.1016/j.bmcl.2004.12.073

Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2

Bioorg Med Chem Lett. 2005 Feb 15;15(4):863-7. doi: 10.1016/j.bmcl.2004.12.073.

Authors

Douglas S Williamson¹, Martin J Parratt, Justin F Bower, Jonathan D Moore, Christine M Richardson, Pawel Dokurno, Andrew D Cansfield, Geraint L Francis, Richard J Hebdon, Rob Howes, Philip S Jackson, Andrea M Lockie, James B Murray, Claire L Nunns, Jenifer Powles, Alan Robertson, Allan E Surgenor, Christopher J Torrance

Affiliation

¹ Vernalis (R&D) Ltd, Granta Park, Great Abington, Cambridge CB1 6GB, United Kingdom. [email protected]

PMID: 15686876
DOI: 10.1016/j.bmcl.2004.12.073

Abstract

The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some examples were shown to inhibit the growth of human colon tumour cells, were equipotent for CDK1 and were selective against GSK-3beta and other kinases.

MeSH terms

CDC2 Protein Kinase / antagonists & inhibitors
CDC2-CDC28 Kinases / antagonists & inhibitors*
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase 2
Drug Design
Humans
Inhibitory Concentration 50
Models, Molecular
Pyrimidines / chemistry*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Pyrimidines
CDC2 Protein Kinase
CDC2-CDC28 Kinases
CDK2 protein, human
Cyclin-Dependent Kinase 2