1064680-92-7

Upstream product

• 1064681-42-0 3-(2-methoxy-6-(3-methoxyphenyl)naphthalen-1-yl)aniline 
• 1041115-67-6 1-bromo-2-methoxy-6-(3-methoxyphenyl)naphthalene 
• 5111-65-9 2-Bromo-6-methoxynaphthalene 
• 66996-59-6 1,6-dibromo-2-methoxynaphthalene 

Downstream Products

• 1064680-97-2 N-{3-[2-hydroxy-6-(3-hydroxyphenyl)-1-naphthyl]phenyl}quinoline-8-sulfonamide 
• 1064681-06-6 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-4-bromo-2-trifluoromethoxybenzenesulfonamide 
• 1064681-11-3 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)thiophene-2-sulfonamide 
• 1064680-98-3 5-chloro-N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)thiophene-2-sulfonamide 
• 1365957-76-1 5-chloro-N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-6aH-pyrrolo[3,2-d]thiazole-6-sulfonamide 
• 1365957-78-3 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)quinolin-6-sulfonamide 
• 1064681-09-9 4,5-dibromo-N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)thiophene-2-sulfonamide 
• 1064681-07-7 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-2-nitro-4-(trifluoromethyl)benzenesulfonamide 
• 1064681-00-0 2-cyano-N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)benzenesulfonamide 
• 1064680-99-4 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-3-nitrobenzenesulfonamide 
• 1064681-05-5 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-4-nitrobenzenesulfonamide 
• 1064681-04-4 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-5-(2-(methylthio)pyrimidin-4-yl)thiophene-2-sulfonamide 
• 1064681-02-2 methyl 5-(N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)sulfamoyl)-4-methoxythiophene-3-carboxylate 
• 1064681-10-2 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)benzo[d]thiazole-6-sulfonamide 

Relevant academic research and scientific papers

Lead optimization of 17β-HSD1 inhibitors of the (hydroxyphenyl) naphthol sulfonamide type for the treatment of endometriosis

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.

New drug-like hydroxyphenylnaphthol steroidomimetics as potent and selective 17β-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of estrogen-dependent diseases

Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17β-HSD1 inhibitors from the hydroxyphenylnaphthol class, structural optimizations were performed at the 1-position of the naphthalene by introduction of different heteroaromatic rings as well as substituted phenyl groups. In the latter class of compounds, which were synthesized applying Suzuki-cross coupling, the 3-methanesulfonamide 15 turned out to be a highly potent 17β-HSD1 inhibitor (IC50 = 15 nM in a cell-free assay). It was also very active in the cellular assay (T47D cells, IC50 = 71 nM) and selective toward 17β-HSD2 and the estrogen receptors α and β. It showed a good membrane permeation and metabolic stability and was orally available in the rat.

17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS FOR THE TREATMENT OF HORMONE-RELATED DISEASES

The invention relates to the use of non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment and prophylaxis of hormone-dependent, particularly estrogen-dependent, diseases.The invention further relates to suitable inhibitors and to a method for the production thereof.