Design, palladium-catalyzed synthesis, and biological investigation of 2-substituted 3-aroylquinolin-4(1H)-ones as inhibitors of the Hedgehog signaling pathway.
01 Pubblicazione su rivista
Alfonsi Romina, Botta Bruno, Cacchi Sandro, DI MARCOTULLIO Lucia, Fabrizi Giancarlo, Faedda Roberta, Goggiamani Antonella, Iazzetti Antonia, Mori Mattia
ISSN: 0022-2623
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.