A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors

Lucie Vandromme; Michel Legraverend; Sergio Kreimerman; Olivier Lozach; Laurent Meijer; David S Grierson

doi:10.1016/j.bmc.2006.10.003

A Pd(0) based cross-coupling approach to the synthesis of 2-amidopurines and their evaluation as CDK inhibitors

Bioorg Med Chem. 2007 Jan 1;15(1):130-41. doi: 10.1016/j.bmc.2006.10.003. Epub 2006 Oct 6.

Authors

Lucie Vandromme¹, Michel Legraverend, Sergio Kreimerman, Olivier Lozach, Laurent Meijer, David S Grierson

Affiliation

¹ UMR 176, Institut Curie, Bât. 110-112, Centre Universitaire, 91405 Orsay, France.

PMID: 17064911
DOI: 10.1016/j.bmc.2006.10.003

Abstract

Two new series of 2-amido- and 2-aminocarbonylpurines have been synthesized using a Pd catalyst cross-coupling reaction either with amides or amines in the presence of CO. Moderate in vitro inhibitory activity against CDK1 and CDK5 was observed with IC(50) of 0.9muM for the most active compound (18c).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2-Aminopurine / analogs & derivatives
2-Aminopurine / chemical synthesis*
2-Aminopurine / pharmacology
Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology*
Animals
CDC2 Protein Kinase / antagonists & inhibitors*
Catalysis
Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
Molecular Structure
Organometallic Compounds / chemistry
Palladium / chemistry*
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology
Purines / chemical synthesis*
Purines / chemistry
Purines / pharmacology*
Stereoisomerism
Structure-Activity Relationship

Substances

9-isopropyl-6-(4-methoxy-benzylamino)-9H-purine-2-carboxylic acid isopropylamide
Amides
Organometallic Compounds
Protein Kinase Inhibitors
Purines
2-Aminopurine
Palladium
Cyclin-Dependent Kinase 5
CDC2 Protein Kinase