Author/Authors :
Kerry L. Sayle، نويسنده , , Johanne Bentley، نويسنده , , F. Thomas Boyle، نويسنده , , A. Hilary Calvert، نويسنده , , Yuzhu Cheng، نويسنده , , Nicola J. Curtin، نويسنده , , Jane A. Endicott and Martin E. M. Noble، نويسنده , , Bernard T. Golding، نويسنده , , Ian R. Hardcastle، نويسنده , , Philip Jewsbury، نويسنده , , Véronique Mesguiche، نويسنده , , David R. Newell، نويسنده , , Martin E. M. Noble، نويسنده , , Rachel J. Parsons، نويسنده , , David J. Pratt، نويسنده , , Lan Z. Wang، نويسنده , , Roger J. Griffin، نويسنده ,
Abstract :
A series of O4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O6-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4′-position were potent inhibitors, with IC50 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.
