Sayle, K. L. et al. (2003) Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2. Bioorganic and Medicinal Chemistry Letters, 13(18), pp. 3079-3082. (doi: 10.1016/S0960-894X(03)00651-6) (PMID:12941338)
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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 40-position were potent inhibitors, with IC50 values against CDK2 of 1.1±10.3 and 34±8 nM, respectively. The crystal structure of the 40-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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sayle, Dr Kerry |
| Authors: | Sayle, K. L., Bentley, J., Boyle, F. T., Calvert, A. H., Cheng, Y., Curtin, N. J., Endicott, J. A., Golding, B. T., Hardcastle, I. R., Jewsbury, P., Mesguiche, V., Newell, D. R., Noble, M. E.M., Parsons, R. J., Pratt, D. J., Wang, L. Z., and Griffin, R. J. |
| College/School: | College of Science and Engineering > Scottish Universities Environmental Research Centre |
| Journal Name: | Bioorganic and Medicinal Chemistry Letters |
| Journal Abbr.: | Bioorg. Med. Chem. Lett. |
| Publisher: | Elsevier |
| ISSN: | 0960-894X |
| Published Online: | 01 August 2003 |
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