Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases

Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors

“…Since h17β-HSD1 is the biological counterpart of h17β-HSD2, catalyzing the opposite conversion, selectivity toward this enzyme is an important feature to take into consideration. Potent and selective h17β-HSD1inhibitors have also been described for the treatment of estrogen-dependent diseases [15,16].…”

Direct antiproliferative effect of nonsteroidal 17β-hydroxysteroid dehydrogenase type 1 inhibitors in vitro

“…Although representing different chemical classes, the chosen 17β-HSD1 inhibitors, designed as steroidomimetics, all share a hydrophobic central core, mimicking the B and C steroidal ring, and two phenolic substituents, mimicking the two polar oxygens of estrone. In the optimization process to increase their potency, it appeared that these moieties are necessary for high 17β-HSD1 inhibition 4,6,8 . These 10 compounds differ in the nature of the hydrophobic central core, which influence not only the electronic density on the whole compound but also the overall geometry of the compounds: Thiophene 1-4, thiazole 5 and phenyl rings 6 lead to a linear shape while the derivatives 7-10 with a naphthalene group are more globular.…”

“…The present aim was to characterize the direct antiproliferative action of a set of previously synthesized nonsteroidal compounds with excellent 17β-HSD1 inhibitory capacity (IC 50 values: 8-143 nM [4][5][6][7][8][9][10] ). All of the tested agents possessed a hydroxyphenyl structural moiety and were therefore chemically related to a wide range of natural polyphenol compounds (e.g.…”

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

“…Both steroidal [18,19] and non-steroidal [20][21][22][23][24][25][26][27][28][29][30][31] 17β-HSD1 inhibitors have been described in the past. Recently we reported on bicyclic substituted hydroxyphenylmethanones [32] (general structure, fig.…”