Novel steroid mimics: synthesis of tri- and tetra-substituted oxamides and oxoamides

A series of dicarbonyl compounds have been designed and prepared to mimic the rigid tetracyclic core of estradiol and dihydrotestosterone. Non-symmetrical tri- and tetra-substituted oxamides were prepared by the sequential addition of primary and secondary amines to phenyl cholorooxoacetate. Oxoamides were prepared via a Friedel–Crafts acylation/amide coupling protocol. Crystallographic data shows a good correlation between the structure of the dicarbonyl mimic and dihydrotestosterone complexed with the androgen receptor suggesting the molecular scaffolds may well prove versatile platforms for ligand design.