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Design and synthesis of a new class of inhibitors for the treatment of osteoporosis and its comparative  h 17 β -HSD2 and  m 17 β -HSD2 SAR study are described.  17a  is the first compound to show strong inhibition of both  h 17 β -HSD2 and  m 17 β -HSD2, intracellular activity, metabolic stability, selectivity toward  h 17 β -HSD1,  m 17 β -HSD1 and estrogen receptors  α  and  β  as well as appropriate physicochemical properties for oral bioavailability. These properties make it eligible for pre-clinical animal studies, prior to human studies.

plos one

17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog