1184108-75-5

Upstream product

• 41789-95-1 1-(3-methoxyphenyl)-N-methylmethanamine 
• 586-75-4 4-chlorobenzoyl chloride 

Downstream Products

• 1350734-93-8 3'-methoxy-N-(3-methoxybenzyl)-N-methyl[1,1'-biphenyl]-4-carboxamide 
• 1350734-94-9 3'-hydroxy-N-(3-hydroxybenzyl)-N-methyl[1,1'-biphenyl]-4-carboxamide 
• 1350734-95-0 N-(3-methoxybenzyl)-n,3'-dimethyl[1,1'-biphenyl]-4-carboxamide 
• 1350734-96-1 N-(3-hydroxybenzyl)-n,3'-dimethyl[1,1'-biphenyl]-4-carboxamide 

Relevant academic research and scientific papers

17β-hydroxysteroid dehydrogenase type 2 inhibition: Discovery of selective and metabolically stable compounds inhibiting both the human enzyme and its murine ortholog

Design and synthesis of a new class of inhibitors for the treatment of osteoporosis and its comparative h17β-HSD2 and m17β-HSD2 SAR study are described. 17a is the first compound to show strong inhibition of both h17β-HSD2 and m17β-HSD2, intracellular activity, metabolic stability, selectivity toward h17β-HSD1, m17β-HSD1 and estrogen receptors α and β as well as appropriate physicochemical properties for oral bioavailability. These properties make it eligible for pre-clinical animal studies, prior to human studies. Copyright:

BIARYL DERIVATIVES AS SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 INHIBITORS

The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors of formula (I), their production and use, notably for the treatment and prophylaxis of sex steroid deficient diseases like osteoporosis in men and women.

Triazole ring-opening leads to the discovery of potent nonsteroidal 17β-hydroxysteroid dehydrogenase type 2 inhibitors

17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyzes the oxidation of the highly potent steroids: the estrogen estradiol (E2) and the androgen testosterone (T) to the less active estrone and androstenedione, respectively. Inhibition of this enzyme may help maintain the local E2 level in bone tissue when the circulating E2 level drops and is therefore a novel and promising approach for the treatment of osteoporosis. In this work, a series of new nonsteroidal and achiral 17β-HSD2 inhibitors, namely N-benzyl-diphenyl-3(or 4)-carboxamide and N-benzyl-5-phenyl-thiophene-2- carboxamide was designed and the compounds were synthesized in a two to three steps reaction. A small library was built applying parallel synthesis. Highly potent 17β-HSD2 inhibitors could be identified in the thiophene-2- carboxamide class with IC50 in the low nanomolar range. These compounds also showed a good selectivity profile toward 17β-HSD1 and toward the estrogen receptors α and β. The most interesting 17β-HSD2 inhibitor identified in this study is the 5-(2-fluoro-3-methoxyphenyl)-N-(3- hydroxybenzyl)-N-methylthiophene-2-carboxamide 6w displaying an IC50 of 61 nM and a selectivity factor of 73 toward 17β-HSD1.