1365958-59-3Relevant articles and documents
Lead optimization of 17β-HSD1 inhibitors of the (hydroxyphenyl) naphthol sulfonamide type for the treatment of endometriosis
Henn, Claudia,Einspanier, Almuth,Marchais-Oberwinkler, Sandrine,Frotscher, Martin,Hartmann, Rolf W.
, p. 3307 - 3318 (2012/06/01)
The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17β-HSD1. For the species-specific optimization of the (hydroxyphenyl)naphthols, a combinatorial approach was applied and enhanced by a focused synthesis that resulted in the aromatic-substituted (hydroxyphenyl)naphthol sulfonamides. Rigidification of 12 led to the 4-indolylsulfonamide 30, which is a highly active and selective human 17β-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17β-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors I?± and β and good intracellular activity (T47D). Thus, compound 30 shows good properties for further ADMET studies and might be a candidate for the in vivo proof of concept in C. jacchus.