1262388-21-5Relevant articles and documents
New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases
Marchais-Oberwinkler, Sandrine,Wetzel, Marie,Ziegler, Erika,Kruchten, Patricia,Werth, Ruth,Henn, Claudia,Hartmann, Rolf W.,Frotscher, Martin
supporting information; experimental part, p. 534 - 547 (2011/03/21)
Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17β-HSD1 inhibitors from the hydroxyphenylnaphthol class, structural optimizations were performed at the 1-position of the naphthalene by introduction of different heteroaromatic rings as well as substituted phenyl groups. In the latter class of compounds, which were synthesized applying Suzuki-cross coupling, the 3-methanesulfonamide 15 turned out to be a highly potent 17β-HSD1 inhibitor (IC50 = 15 nM in a cell-free assay). It was also very active in the cellular assay (T47D cells, IC50 = 71 nM) and selective toward 17β-HSD2 and the estrogen receptors α and β. It showed a good membrane permeation and metabolic stability and was orally available in the rat.
