Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Estradiol Dehydrogenases / antagonists & inhibitors*
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Humans
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Mice
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Estradiol Dehydrogenases
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HSD17B2 protein, human
Grants and funding
The authors acknowledge the Deutsche Forschungsgemeinschaft (DFG) for financial support (Grants HA1315/12-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Elexopharm GmbH had no financial interest in this collaboration.