1326702-91-3Relevant academic research and scientific papers
Development of 3-substituted-androsterone derivatives as potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3
Maltais, Rene,Fournier, Michelle-Audrey,Poirier, Donald
experimental part, p. 4652 - 4668 (2011/09/12)
17Beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a steroidogenic enzyme that catalyzes the transformation of 4-androstene-3,17- dione (Δ4-dione) into androgen testosterone (T). To provide effective inhibitors of androgen biosynthesis, we synthesized two different series (amines and carbamates) of 3β-substituted-androsterone derivatives and we tested their inhibitory activity on 17β-HSD3. From the results of our structure-activity relationship study, we identified a series of compounds producing a strong inhibition of 17β-HSD3 overexpressed in HEK-293 cells (homogenized cells). The most active compound when tested in intact HEK-293 transfected cells, namely (3α,5α)-3-{[trans-2,5-dimethyl-4-{[2- (trifluoromethyl)phenyl] sulfonyl}piperazin-1-yl]methyl}-3-hydroxyandrostan-17- one (15b), shows an IC50 value of 6 nM, this compound is thus eight times more active than our reference compound D-5-2 (IC50 = 51 nM). This new improved inhibitor did not stimulate the proliferation of androgen-sensitive Shionogi cells, suggesting a non-androgenic profile. Compound 15b is thus a good candidate for further in vivo studies on rodents.
