Novel steroid mimics directed towards the estradiol skeleton

A series of non-symmetrical tri- and tetra-substituted ureas have been prepared to mimic the rigid tetracyclic core of estradiol. Tetra-substituted ureas were prepared by a five-step protocol, involving activation and displacement of a carbonyldiimidazole adduct in 48–67% overall yield. This method was unsuccessful for tri-substituted ureas, which were prepared in 42–74% yields by an alternative four-step method, which included a one-pot 4-nitrophenyl carbamate formation/displacement sequence.