Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR.
Article Details
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Richardson CM, Williamson DS, Parratt MJ, Borgognoni J, Cansfield AD, Dokurno P, Francis GL, Howes R, Moore JD, Murray JB, Robertson A, Surgenor AE, Torrance CJ
Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR.
Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7. Epub 2005 Dec 1.
- PubMed ID
- 16325401 [ View in PubMed]
- Abstract
Crystallographic and modelling data, in conjunction with a medicinal chemistry template-hopping approach, led to the identification of a series of novel and potent inhibitors of human cyclin-dependent kinase 2 (CDK2), with selectivity over glycogen synthase kinase-3beta (GSK-3beta). One example had a CDK2 IC(50) of 120 nM and showed selectivity over GSK-3beta of 167-fold.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Cyclin-dependent kinase 2 P24941 Details - Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-({5-[(4-AMINOCYCLOHEXYL)AMINO][1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)BENZENESULFONAMIDE Cyclin-dependent kinase 2 IC 50 (nM) 270 7.5 22 Details 4-{[5-(CYCLOHEXYLAMINO)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDE Cyclin-dependent kinase 2 IC 50 (nM) 730 7.5 22 Details 4-{[5-(CYCLOHEXYLMETHOXY)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDE Cyclin-dependent kinase 2 IC 50 (nM) 11000 7.5 22 Details 4-{[5-(CYCLOHEXYLOXY)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDE Cyclin-dependent kinase 2 IC 50 (nM) 350 7.5 22 Details TRIAZOLOPYRIMIDINE Cyclin-dependent kinase 2 IC 50 (nM) 26000 7.5 22 Details