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
New Journal of Chemistry
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.
Mader, Lavleen; Hayward, John J.; Porter, Lisa A.; and Trant, John F.. (2022). A revised synthesis of 6-alkoxy-2-aminopurines with late-stage convergence allowing for increased molecular complexity†. New Journal of Chemistry, 2022 (35), 17040-17048.
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