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dc.contributor.authorAbdelsamie, Ahmed S
dc.contributor.authorBey, Emmanuel
dc.contributor.authorHanke, Nina
dc.contributor.authorEmpting, Martin
dc.contributor.authorHartmann, Rolf W
dc.contributor.authorFrotscher, Martin
dc.date.accessioned2014-08-19T09:52:53Z
dc.date.available2014-08-19T09:52:53Z
dc.date.issued2014-07-23
dc.identifier.citationInhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker. 2014, 82:394-406 Eur J Med Chemen
dc.identifier.issn1768-3254
dc.identifier.pmid24929290
dc.identifier.doi10.1016/j.ejmech.2014.05.074
dc.identifier.urihttp://hdl.handle.net/10033/324967
dc.description.abstractEstradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β- HSD1) which consequently is a promising target for the treatment of these diseases. Recently, we reported on bicyclic substituted hydroxyphenylmethanones as potent inhibitors of 17β-HSD1. The present study focuses on rational structural modifications in this compound class with the aim of gaining more insight into its structure-activity relationship (SAR). (4-Hydroxyphenyl)-(5-(3-hydroxyphenylsulfanyl)-thiophen-2-yl)methanone (25) was discovered as a member of a novel potent class of human 17β-HSD1 inhibitors. Computational methods were used to elucidate its interactions with the target protein. The compound showed activity also towards the murine 17β-HSD1 enzyme and thus is a starting point for the design of compounds suitable for evaluation in an animal disease model.
dc.language.isoenen
dc.rightsArchived with thanks to European journal of medicinal chemistryen
dc.titleInhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.en
dc.typeArticleen
dc.identifier.journalEuropean journal of medicinal chemistryen
refterms.dateFOA2018-06-13T09:09:56Z
html.description.abstractEstradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β- HSD1) which consequently is a promising target for the treatment of these diseases. Recently, we reported on bicyclic substituted hydroxyphenylmethanones as potent inhibitors of 17β-HSD1. The present study focuses on rational structural modifications in this compound class with the aim of gaining more insight into its structure-activity relationship (SAR). (4-Hydroxyphenyl)-(5-(3-hydroxyphenylsulfanyl)-thiophen-2-yl)methanone (25) was discovered as a member of a novel potent class of human 17β-HSD1 inhibitors. Computational methods were used to elucidate its interactions with the target protein. The compound showed activity also towards the murine 17β-HSD1 enzyme and thus is a starting point for the design of compounds suitable for evaluation in an animal disease model.


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