Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors

The design, synthesis, and biological evaluation of new analogs of the naturally occurring compound cyclopamine, a hedgehog signaling inhibitor, are described. Structure-activity relationship studies lead to an evolving model for the pharmacophore of this medically promising compound class of anti-cancer chemotherapeutic agents.

The design synthesis, and biological evaluation of 6, 7, 8, and 16, which serve as mimics of the potent hedgehog inhibiting substance cyclopamine 1, are described.