Ruthenium half-sandwich complexes as protein kinase inhibitors: derivatization of the pyridocarbazole pharmacophore ligand

A general route to ruthenium pyridocarbazole half-sandwich complexes is presented and applied to the synthesis of sixteen new compounds, many of which have modulated protein kinase inhibition properties. For example, the incorporation of a fluorine into the pyridine moiety increases the binding affinity for glycogen synthase kinase 3 by almost one order of magnitude. These data are supplemented with cyclic voltammetry experiments and a protein co-crystallographic study.