A series of O 4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O 6-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4′-position were potent inhibitors, with IC 50 values against CDK2 of 1.1±0.3 and 34±8 nM, respectively. The crystal structure of the 4′-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue. A series of O 4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O 6-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4′-position were potent inhibitors, with IC 50 values against CDK2 of 1.1±0.3 and 35±8 nM, respectively. The crystal structure of the 4′-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.