Chemical Modification of 2,6,9-Trisubstituted Purine CDK Inhibitors: tert-Butylation at N7/N9 and Access to 2,6,7-Trisubstituted Analogs.

Authors

Michal Valenta, Jakub Stýskala

Published in

ACS omega. Volume 11. Issue 16. Pages 23833-23844. Apr 28, 2026. Epub Apr 14, 2026.

Abstract

This study focuses on the chemical modification of known 2,6,9-trisubstituted purine cyclin-dependent kinase (CDK) inhibitors as model compounds, with particular emphasis on the incorporation of the less-explored tert-butyl group (representing tert-alkyl substituents) at the N7 and N9 positions of the purine core to prepare 2,6,7- and 2,6,9-trisubstituted analogs. Primarily chemical aspects of these modifications are studied, focusing on the effect of the tert-butyl group on chlorine reactivity at C2/C6 position and purine ring stability during substitution reactions, especially in the case of 2,6,7-trisubstituted compounds. The effect of the tert-butyl group is also evaluated in comparison with other substituents at the purine ring. Furthermore, a novel and unambiguous synthetic route to key intermediates -7 and 9-(tert-butyl)-2,6-dichloropurines-has been developed by a new method to enable targeted substitution at the chlorine-bearing positions.

PMID:
42077863
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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