Design, synthesis and evaluation of novel tetrahydrothieno[3,2-c]pyridine derivatives as potent smoothened antagonists

Abstract

Hedgehog (Hh) signalling plays an important role in embryonic development and adult tissue homeostasis. Since activation of the Hh signalling pathway is implicated in several types of human cancers, inhibitors of this pathway could be promising anticancer agents. The smoothened (Smo) receptor mediates Hh signalling. In the present study, we synthesised a series of novel tetrahydrothieno[3,2-c]pyridine derivatives using a scaffold hopping strategy. Compounds with this novel scaffold demonstrated promising Hh and Smo inhibition, indicating that this novel scaffold can serve as a starting point for further optimisation.