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.

Graphical abstractA series of novel dicarbonyl compounds have been designed to mimic the tetracyclic core of steroids.Figure optionsDownload full-size imageDownload as PowerPoint slide