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Lookup NU author(s): Kerry Louise Sayle, Dr Johanne Bentley, Professor Alan Calvert, Dr YuZhu Cheng, Professor Nicola CurtinORCiD, Professor Jane Endicott, Emeritus Professor Bernard Golding, Dr Ian HardcastleORCiD, Dr Veronique Mesguiche, Professor Herbie Newell, Professor Martin NobleORCiD, Rachel Parsons, Lan Wang, Professor Roger Griffin
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 O 6-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. © 2003 Elsevier Ltd. All rights reserved.
Author(s): Sayle, K., Bentley, J., Boyle, F., Calvert, A. H., Cheng, Y., Curtin, N. J., Endicott, J., Golding, B., Hardcastle, I., Jewsbury, P., Mesguiche, V., Newell, D. R., Noble, M., Parsons, R., Pratt, D., Wang, L., Griffin, R. J.
Publication type: Article
Publication status: Published
Journal: Bioorganic and Medicinal Chemistry Letters
Year: 2003
Volume: 13
Issue: 18
Pages: 3079-3082
Print publication date: 15/09/2003
ISSN (print): 0960-894X
ISSN (electronic): 1464-3405
URL: http://dx.doi.org/10.1016/S0960-894X(03)00651-6
DOI: 10.1016/S0960-894X(03)00651-6
PubMed id: 12941338
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