Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: Protein structure-guided design and SAR

Crystallographic and modelling data, in conjunction with a medicinal chemistry template-hopping approach, led to the identification of a series of novel and potent inhibitors of human cyclin-dependent kinase 2 (CDK2), with selectivity over glycogen synthase kinase-3β (GSK-3β). One example had a CDK2 IC50 of 120 nM and showed selectivity over GSK-3β of 167-fold.

Graphical abstractCrystallographic and modelling data, in conjunction with a medicinal chemistry template-hopping approach, led to the identification of a series of novel and potent inhibitors of human cyclin-dependent kinase 2 (CDK2), with selectivity over glycogen synthase kinase-3β (GSK-3β). One example had a CDK2 IC50 of 120 nM and showed selectivity over GSK-3β of 167-fold.Figure optionsDownload full-size imageDownload as PowerPoint slide