Structure-Guided Discovery of Novel -(Substituted Thiazol-2-yl)--(4-Substituted phenyl)pyrimidine-2,4-Diamines as Potent CDK2 and CDK9 Dual Inhibitors with High Oral Bioavailability.

CDK2 and CDK9 play pivotal roles in cell cycle progression and gene transcription, respectively, making them promising targets for cancer treatment. Herein, we discovered a series of -(substituted thiazol-2-yl)--(4-substituted phenyl)pyrimidine-2,4-diamines as highly potent CDK2/9 dual inhibitors. Especially, compound significantly inhibited CDK2 (IC = 0.