Synthesis and antihormonal properties of novel 11β-benzoxazole-substituted steroids

Early studies led to the identification of 11β-aryl-4′,5′-dihydrospiro[estra-4,9-diene-17β,4′-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4′-dimethylaminophenyl group of mifepristone with the benzoxazol group to give 5a–d. We also prepared the 17β-formamido analogs 6a,b using a new synthetic strategy via the intermediate epoxide 21. These compounds were evaluated for their antagonist hormonal properties using the T47D cell-based alkaline phosphatase assay and the A549 cell-based functional assay. Compound 5c showed potent antagonist activity at GR with better selectivity for GR versus PR than mifepristone and is a promising lead for further development.

Graphical abstractA series of novel 11β-benzoxazole-substituted 17β-hydroxy- or 17β-formamido-steroids were synthesized and evaluated for their antihormonal properties.Figure optionsDownload full-size imageDownload as PowerPoint slide