Inhibitory effects of fluorine-substituted estrogens on the activity of 17beta-hydroxysteroid dehydrogenases

In search for new inhibitors of human 17beta-hydroxysteroid dehydrogenase type 1 (h17β-HSD1) a specific group of steroids with interesting properties including novel compounds was investigated. Several estratriene derivatives with fluorine-substitution in position 17 of the steroidal scaffold were synthesised and tested in vitro towards recombinant h17β-HSD1, 2, 4, 5 and 7. Moderate, mostly unselective inhibitors of h17β-HSD1 and h17β-HSD2 and a selective inhibitor of h17β-HSD5 were identified. The structure–activity relationship with respect to inhibitory strengths and selectivity of these compounds on five h17β-HSDs is discussed.