Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2003 |
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| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Bioorganic & medicinal chemistry letters - 13(2003), 18 vom: 15. Sept., Seite 3079-82 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sayle, Kerry L [VerfasserIn] |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 21.05.2004 Date Revised 19.08.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM126912025 |
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| 100 | 1 | |a Sayle, Kerry L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2 |
| 264 | 1 | |c 2003 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 21.05.2004 | ||
| 500 | |a Date Revised 19.08.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a CDC2 Protein Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a CDC2-CDC28 Kinases |2 NLM | |
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| 650 | 7 | |a CDK2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 2 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.22 |2 NLM | |
| 700 | 1 | |a Bentley, Johanne |e verfasserin |4 aut | |
| 700 | 1 | |a Boyle, F Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Calvert, A Hilary |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Yuzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Curtin, Nicola J |e verfasserin |4 aut | |
| 700 | 1 | |a Endicott, Jane A |e verfasserin |4 aut | |
| 700 | 1 | |a Golding, Bernard T |e verfasserin |4 aut | |
| 700 | 1 | |a Hardcastle, Ian R |e verfasserin |4 aut | |
| 700 | 1 | |a Jewsbury, Philip |e verfasserin |4 aut | |
| 700 | 1 | |a Mesguiche, Veronique |e verfasserin |4 aut | |
| 700 | 1 | |a Newell, David R |e verfasserin |4 aut | |
| 700 | 1 | |a Noble, Martin E M |e verfasserin |4 aut | |
| 700 | 1 | |a Parsons, Rachel J |e verfasserin |4 aut | |
| 700 | 1 | |a Pratt, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lan Z |e verfasserin |4 aut | |
| 700 | 1 | |a Griffin, Roger J |e verfasserin |4 aut | |
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