17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
oleh: Emanuele M Gargano, Giuseppe Allegretta, Enrico Perspicace, Angelo Carotti, Chris Van Koppen, Martin Frotscher, Sandrine Marchais-Oberwinkler, Rolf W Hartmann
| Format: | Article |
|---|---|
| Diterbitkan: | Public Library of Science (PLoS) 2015-01-01 |
Deskripsi
Design and synthesis of a new class of inhibitors for the treatment of osteoporosis and its comparative h17β-HSD2 and m17β-HSD2 SAR study are described. 17a is the first compound to show strong inhibition of both h17β-HSD2 and m17β-HSD2, intracellular activity, metabolic stability, selectivity toward h17β-HSD1, m17β-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.