A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a potent CDK2/cyclin A inhibitor

Marcella Nesi; Daniela Borghi; Maria Gabriella Brasca; Francesco Fiorentini; Paolo Pevarello

doi:10.1016/j.bmcl.2006.03.051

A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a potent CDK2/cyclin A inhibitor

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3205-8. doi: 10.1016/j.bmcl.2006.03.051. Epub 2006 Apr 17.

Authors

Marcella Nesi¹, Daniela Borghi, Maria Gabriella Brasca, Francesco Fiorentini, Paolo Pevarello

Affiliation

¹ Department of Chemistry, Oncology Business Unit, Nerviano Medical Sciences, Viale Pasteur 10-20014 Nerviano, MI, Italy. [email protected]

PMID: 16616492
DOI: 10.1016/j.bmcl.2006.03.051

Abstract

The synthesis of the major metabolite of a potent 3-aminopyrazole CDK2/cyclin A inhibitor is presented. A stereoconservative approach starting from malic acid was employed to construct the hydroxy-substituted pyrrolidinone moiety. In the key step of the synthesis the use of cyanoborohydride immobilized on Amberlyst 26 in trifluoroethanol represented a valid alternative to conventional solution-phase reducing agents.

MeSH terms

Animals
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin A / antagonists & inhibitors*
Cyclin A / metabolism
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
Cyclin-Dependent Kinase 2 / metabolism
Humans
Mass Spectrometry
Molecular Structure
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Pyrrolidinones / chemistry*
Pyrrolidinones / metabolism
Pyrrolidinones / pharmacology*

Substances

3-hydroxy-2-pyrrolidinone
Cyclin A
Protein Kinase Inhibitors
Pyrrolidinones
Cyclin-Dependent Kinase 2