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

ABSTRACT: Design and synthesis of a new class of inhibitors for the treatment of osteoporosis and its comparative h17?-HSD2 and m17?-HSD2 SAR study are described. 17a is the first compound to show strong inhibition of both h17?-HSD2 and m17?-HSD2, intracellular activity, metabolic stability, selectivity toward h17?-HSD1, m17?-HSD1 and estrogen receptors ? and ? as well as appropriate physicochemical properties for oral bioavailability. These properties make it eligible for pre-clinical animal studies, prior to human studies.

SUBMITTER: Gargano EM

PROVIDER: S-EPMC4521925 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Gargano Emanuele M EM Allegretta Giuseppe G Perspicace Enrico E Carotti Angelo A Van Koppen Chris C Frotscher Martin M Marchais-Oberwinkler Sandrine S Hartmann Rolf W RW

PloS one 20150731 7

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, pri ...[more]

PMID: 26230928

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