| Abstract
| - Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibitcyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue ofthe 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysisof the lead compound bound to CDK2 provided the basis for analogue design. A semiautomatedmethod of ligand docking was used to select compounds for synthesis, and a number ofcompounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzymebinding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency ∼10-fold greater than that for CDK1.Members of this class of inhibitor cause an arrest of the cell cycle and have shown potentialutility in the prevention of chemotherapy-induced alopecia.
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