Synthesis and Evaluation of [2-(4-Quinolyloxy)phenyl]methanone Derivatives: Novel Selective Inhibitors of Transforming Growth Factor-β Kinase

We synthesized and evaluated various [2-(4-quinolyloxy)phenyl]methanone derivatives. These compounds had novel chemical structures that were distinct from those of previously reported inhibitors. Biological data suggested that these compounds inhibited transforming growth factor-beta signaling by interacting with the ATP-binding pocket of the transforming growth factor-beta type I receptor kinase domain. Here, we report on the synthesis and structure-activity relationships of the compounds in this series.