Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. Part 4: Heterocycles at C3

Eddy W Yue; Susan V DiMeo; C Anne Higley; Jay A Markwalder; Catherine R Burton; Pamela A Benfield; Robert H Grafstrom; Sarah Cox; Jodi K Muckelbauer; Angela M Smallwood; Haiying Chen; Chong Hwan Chang; George L Trainor; Steven P Seitz

doi:10.1016/j.bmcl.2003.11.008

Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. Part 4: Heterocycles at C3

Bioorg Med Chem Lett. 2004 Jan 19;14(2):343-6. doi: 10.1016/j.bmcl.2003.11.008.

Authors

Eddy W Yue¹, Susan V DiMeo, C Anne Higley, Jay A Markwalder, Catherine R Burton, Pamela A Benfield, Robert H Grafstrom, Sarah Cox, Jodi K Muckelbauer, Angela M Smallwood, Haiying Chen, Chong Hwan Chang, George L Trainor, Steven P Seitz

Affiliation

¹ Bristol-Myers Squibb Company, Experimental Station, PO Box 80500, Wilmington, DE 19880-0500, USA. eddyyue@incyte.com

PMID: 14698155
DOI: 10.1016/j.bmcl.2003.11.008

Abstract

New indeno[1,2-c]pyrazol-4-one cyclin dependent kinase inhibitors have been disclosed. The most promising compounds are nanomolar enzyme inhibitors with excellent activity against tumor cells. The most advanced compound retains cell culture activity even in the presence of human serum proteins. The most advanced compound did not kill the normal fibroblast line AG1523.

MeSH terms

Cell Line, Tumor
Cyclin-Dependent Kinases / antagonists & inhibitors*
Cyclin-Dependent Kinases / metabolism
Drug Evaluation, Preclinical / methods
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Fibroblasts / drug effects
Fibroblasts / enzymology
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / pharmacology
Humans
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology

Substances

Enzyme Inhibitors
Heterocyclic Compounds
Pyrazoles
Cyclin-Dependent Kinases