Discovery of a new class of bicyclic substituted hydroxyphenylmethanones as 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors for the treatment of osteoporosis

Inhibitors of 17β-hydroxysteroid dehydrogenase type 1, 2 and 14: Structures, biological activities and future challenges

“…Benzene derivatives were more potent but less selective than their pyridine analogs while the latter showed more favorable combinations of activity and selectivity. The most interesting compound in this work was compound 78 (Wetzel et al 2012).…”

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

“…In our group we also developed and reported about several classes of non-steroidal 17β-HSD2 inhibitors [10][11][12][13][14], with a strong inhibition of human 17β-hydroxysteroid dehydrogenase type 2 (h17β-HSD2) and a good selectivity toward h17β-HSD1. 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.…”

Suzuki‐Miyaura Cross‐Coupling of Amides using Well‐Defined, Air‐Stable [(PR3)2Pd(II)X2] Precatalysts

“…Furthermore, [(dppb)PdCl 2 ] resulted in unsuccessful reaction (Table 1, entry 16). It should be pointed out that since the classic studies by Kumada, [15] [16][17][18][19][20][21] resulted in moderate conversions, thus providing a promising entry point for future studies. We hypothesize that the use of [(PCy 3 ) 2 PdCl 2 ] is optimal in the amide cross-coupling due to combining electron-rich nature of trialkylphosphine with favorable steric properties of PCy 3 .…”

“…We demonstrated that the present protocol can be readily employed to access pharmaceutical intermediates by sequential orthogonal aryl halide/amide NÀ C(O) cross-coupling (Scheme 4). Thus, an intermediate in the synthesis 17β-HSD2 inhibitors for the treatment of osteoporosis [18] was prepared in 87% combined yield without isolation of the intermediate amide. Importantly, full selectivity in the biaryl cross-coupling using the conventional Pd (PPh 3 ) 4 was observed in the presence of sensitive amide bond, which was then cross-coupled using [(PCy 3 ) 2 PdCl 2 ] without modification of the reaction conditions.…”