Title of article
Structure-Based design of 2-Arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-Dependent kinases 1 and 2
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 ,
Issue Information
روزنامه با شماره پیاپی سال 2003
Pages
4
From page
3079
To page
3082
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.
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2003
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
793513
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