Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR.

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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
NameUniProt ID
Cyclin-dependent kinase 2P24941Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
4-({5-[(4-AMINOCYCLOHEXYL)AMINO][1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL}AMINO)BENZENESULFONAMIDECyclin-dependent kinase 2IC 50 (nM)2707.522Details
4-{[5-(CYCLOHEXYLAMINO)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDECyclin-dependent kinase 2IC 50 (nM)7307.522Details
4-{[5-(CYCLOHEXYLMETHOXY)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDECyclin-dependent kinase 2IC 50 (nM)110007.522Details
4-{[5-(CYCLOHEXYLOXY)[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-7-YL]AMINO}BENZENESULFONAMIDECyclin-dependent kinase 2IC 50 (nM)3507.522Details
TRIAZOLOPYRIMIDINECyclin-dependent kinase 2IC 50 (nM)260007.522Details