Benzodipyrazoles: a new class of potent CDK2 inhibitors

The synthesis and the preliminary structure–activity relationship results of this class are reported. The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion an...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2005-03, Vol.15 (5), p.1315-1319
Main Authors: D’Alessio, Roberto, Bargiotti, Alberto, Metz, Suzanne, Brasca, M. Gabriella, Cameron, Alexander, Ermoli, Antonella, Marsiglio, Aurelio, Polucci, Paolo, Roletto, Fulvia, Tibolla, Marcellino, Vazquez, Michael L., Vulpetti, Anna, Pevarello, Paolo
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
CDC2-CDC28 Kinases - antagonists & inhibitors
CDK2
Cell Line, Tumor
Cell Proliferation - drug effects
Crystallization
Crystallography, X-Ray
Cyclin A - antagonists & inhibitors
Cyclin-Dependent Kinase 2
Cyclins
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - classification
Enzyme Inhibitors - pharmacology
General aspects
Glycogen Synthase Kinase 3 - antagonists & inhibitors
Humans
Kinase selectivity
Medical sciences
Models, Molecular
Molecular Structure
Pharmacology. Drug treatments
Pyrazoles - chemical synthesis
Pyrazoles - classification
Pyrazoles - pharmacology
Structure-Activity Relationship
Tumor cell proliferation inhibition
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Summary:The synthesis and the preliminary structure–activity relationship results of this class are reported. The synthesis and the preliminary expansion of this new class of CDK2 inhibitors are presented. The synthesis was accomplished using a solution-phase protocol amenable to rapid parallel expansion and suitable to be scaled-up in view of possible lead development. Following a medicinal chemistry program aimed at improving cell permeability and selectivity, a series of compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit tumor cell proliferation has been obtained.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2005.01.023