Author ORCID Identifier

https://orcid.org/0000-0002-9519-2484 : Lavleen Mader

https://orcid.org/0000-0002-7502-7780 : John Hayward

https://orcid.org/0000-0002-9234-1712 : Lisa A. Porter

https://orcid.org/0000-0002-4780-4968 : John F. Trant

Document Type

Article

Publication Date

8-16-2022

Publication Title

New Journal of Chemistry

Volume

2022

Issue

35

First Page

17040

Last Page

17048

Abstract

6-Alkoxy-2-aminopurine derivatives are potent inhibitors of Cyclin Dependent Kinases (CDKs), with some selectivity towards CDK2 and thus have potential as cancer therapeutics. Development of these inhibitors for targeting CDK2-cyclin A/E complexes has previously involved a thorough investigation of structure activity relationships of the C-2 amine moiety. However, the established synthesis of these compounds, which uses the alcohol reagent as solvent, limits the complexity of the O-6 functionality which is required for more selective targeting. Herein we report an improved and refocused synthesis of a model CDK2 inhibitor (NU6247), affording convenient access to inhibitors with O-6 substituents whose parent alcohol is not amenable for use as solvent. This revised synthesis allows for a meaningful exploration of the O-6 position in this class of CDK2 inhibitors.

DOI

10.1039/D2NJ02204D

ISSN

1144-0546

Available for download on Saturday, September 21, 2024

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