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

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 towar...

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Main Authors:	Emanuele M Gargano, Giuseppe Allegretta, Enrico Perspicace, Angelo Carotti, Chris Van Koppen, Martin Frotscher, Sandrine Marchais-Oberwinkler, Rolf W Hartmann
Format:	Article
Language:	English
Published:	Public Library of Science (PLoS) 2015-01-01
Series:	PLoS ONE
Online Access:	http://europepmc.org/articles/PMC4521925?pdf=render

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spelling	doaj-0bc4d2b54c854517a63ff00bf9fcb5c92020-11-24T21:24:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013475410.1371/journal.pone.013475417β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.Emanuele M GarganoGiuseppe AllegrettaEnrico PerspicaceAngelo CarottiChris Van KoppenMartin FrotscherSandrine Marchais-OberwinklerRolf W HartmannDesign 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.http://europepmc.org/articles/PMC4521925?pdf=render
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Emanuele M Gargano Giuseppe Allegretta Enrico Perspicace Angelo Carotti Chris Van Koppen Martin Frotscher Sandrine Marchais-Oberwinkler Rolf W Hartmann
spellingShingle	Emanuele M Gargano Giuseppe Allegretta Enrico Perspicace Angelo Carotti Chris Van Koppen Martin Frotscher Sandrine Marchais-Oberwinkler Rolf W Hartmann 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog. PLoS ONE
author_facet	Emanuele M Gargano Giuseppe Allegretta Enrico Perspicace Angelo Carotti Chris Van Koppen Martin Frotscher Sandrine Marchais-Oberwinkler Rolf W Hartmann
author_sort	Emanuele M Gargano
title	17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
title_short	17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
title_full	17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
title_fullStr	17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
title_full_unstemmed	17β-Hydroxysteroid Dehydrogenase Type 2 Inhibition: Discovery of Selective and Metabolically Stable Compounds Inhibiting Both the Human Enzyme and Its Murine Ortholog.
title_sort	17β-hydroxysteroid dehydrogenase type 2 inhibition: discovery of selective and metabolically stable compounds inhibiting both the human enzyme and its murine ortholog.
publisher	Public Library of Science (PLoS)
series	PLoS ONE
issn	1932-6203
publishDate	2015-01-01
description	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.
url	http://europepmc.org/articles/PMC4521925?pdf=render
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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.

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