Novel glucocorticoid antedrugs possessing a C16,17-fused γ-lactone ring

A series of novel γ-butyrolactones fused at the 16β,17β position of the 9α-fluoro-11β-hydroxy-3-oxoandrosta-1,4-diene nucleus and possessing oxygen substituents at 16α,17α positions were prepared and tested as glucocorticoid agonists. The compounds were also tested for their lability in human plasma. Lactone 5 was found to be rapidly hydrolysed in plasma, whereas derivative 18 was found to be a potent glucocorticoid agonist, but was stable in plasma. The structure of the C21S diastereoisomer of compound 18 was confirmed by an X-ray diffraction study.