Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases.
Thinnes CC., Tumber A., Yapp C., Scozzafava G., Yeh T., Chan MC., Tran TA., Hsu K., Tarhonskaya H., Walport LJ., Wilkins SE., Martinez ED., Müller S., Pugh CW., Ratcliffe PJ., Brennan PE., Kawamura A., Schofield CJ.
There is interest in developing potent, selective, and cell-permeable inhibitors of human ferrous iron and 2-oxoglutarate (2OG) oxygenases for use in functional and target validation studies. The 3-component Betti reaction enables efficient one-step C-7 functionalisation of modified 8-hydroxyquinolines (8HQs) to produce cell-active inhibitors of KDM4 histone demethylases and other 2OG oxygenases; the work exemplifies how a template-based metallo-enzyme inhibitor approach can be used to give biologically active compounds.