Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.

2.50
Hdl Handle:
http://hdl.handle.net/10033/324967
Title:
Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.
Authors:
Abdelsamie, Ahmed S; Bey, Emmanuel; Hanke, Nina; Empting, Martin; Hartmann, Rolf W; Frotscher, Martin
Abstract:
Estradiol 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.
Citation:
Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker. 2014, 82:394-406 Eur J Med Chem
Journal:
European journal of medicinal chemistry
Issue Date:
23-Jul-2014
URI:
http://hdl.handle.net/10033/324967
DOI:
10.1016/j.ejmech.2014.05.074
PubMed ID:
24929290
Type:
Article
Language:
en
ISSN:
1768-3254
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorAbdelsamie, Ahmed Sen
dc.contributor.authorBey, Emmanuelen
dc.contributor.authorHanke, Ninaen
dc.contributor.authorEmpting, Martinen
dc.contributor.authorHartmann, Rolf Wen
dc.contributor.authorFrotscher, Martinen
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.en
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

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