Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2‑Substituted 3‑Aroylquinolin-4(1<i>H</i>)‑ones as Inhibitors of the Hedgehog Signaling Pathway

2-Substituted 3-aroylquinolin-4­(1H)-ones, prepared through a palladium-catalyzed carbonylative cyclization of N-(2-iodoaryl)­enaminones, proved to inhibit efficiently the Hedgehog pathway through direct antagonism of the wild-type and drug-resistant form of the Smoothened receptor. Notably, these compounds repressed the Hh-dependent growth events and the proliferation of tumor cells with aberrant activation of the Hh pathway, which plays a crucial role in development and tumorigenesis.