Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors.
J. Med. Chem. 54, 7547-7557 (2011)
Estrogen deficiency in postmenopausal women or elderly men is often associated with the skeletal disease osteoporosis. The supplementation of estradiol (E2) in osteoporotic patients is known to prevent bone fracture but cannot be administered because of adverse effect. As 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) oxidizes E2 to its inactive form estrone (E1) and has been found in osteoblastic cells, it is an attractive target for the treatment of osteoporosis. Twenty-one novel, naphthalene-derived compounds have been synthesized and evaluated for their 17β-HSD2 inhibition and their selectivity toward 17β-HSD1 and the estrogen receptors (ERs) α and β. Compound 19 turned out to be the most potent and selective inhibitor of 17β-HSD2 in cell-free assays and had a very good cellular activity in MDA-MB-231 cells, expressing naturally 17β-HSD2. It also showed marked inhibition of the E1-formation by the rat and mouse orthologous enzymes and strong inhibition of monkey 17β-HSD2. It is thus an appropriate candidate to be further evaluated in a disease-oriented model.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
no Keywords
ISSN (print) / ISBN
0022-2623
e-ISSN
1520-4804
Journal
Journal of Medicinal Chemistry
Quellenangaben
Volume: 54,
Issue: 21,
Pages: 7547-7557
Publisher
American Chemical Society (ACS)
Publishing Place
Washington, DC
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Molekulare Endokrinologie und Metabolismus (MEM)