1249181-52-9

Upstream product

• 1003-09-4 2-bromothiophene 
• 1711-05-3 m-anisoyl chloride 

Downstream Products

• 1255940-20-5 (3-methoxyphenyl){5-[4-methoxy-3-(trifluoromethyl)phenyl]-2-thienyl}methanone 
• 1226341-15-6 (5-bromothiophene-2-yl)(3-hydroxyphenyl)methanone 
• 1255940-15-8 [5-(3-methoxy-4-methylphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1255940-08-9 (3-methoxyphenyl)[5-(4-methoxyphenyl)-2-thienyl]methanone 
• 1255940-09-0 (3-methoxyphenyl)[5-(2-methoxyphenyl)-2-thienyl]methanone 
• 1255940-21-6 [5-(3,4-dimethoxyphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1255940-19-2 [5-(3-fluoro-4-methoxyphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1255940-18-1 [5-(4-methoxy-3-methylphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1255940-17-0 [5-(2-fluoro-3-methoxyphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1255940-16-9 [5-(4-fluoro-3-methoxyphenyl)-2-thienyl](3-methoxyphenyl)methanone 
• 1361253-01-1 N-{3-[5-(3-methoxybenzoyl)-2-thienyl]benzyl}methanesulfonamide 
• 1283077-29-1 (3-hydroxyphenyl)[5-(4-methoxyphenyl)-2-thienyl]methanone 
• 1283077-30-4 (3-hydroxyphenyl)[5-(6-methoxypyridin-3-yl)-2-thienyl]methanone 
• 1283077-31-5 [5-(3,4-dimethoxyphenyl)-2-thienyl](3-hydroxyphenyl)methanone 

Relevant academic research and scientific papers

Bicyclic Substituted Hydroxyphenylmethanone Type Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type1 (17β-HSD1): The Role of the Bicyclic Moiety

An attractive target that has still to be explored for the treatment of estrogen-dependent diseases, such as breast cancer and endometriosis, is the enzyme responsible for the last step in the biosynthesis of estradiol (E2): 17β-hydroxysteroid dehydrogena

Treatment of estrogen-dependent diseases: Design, synthesis and profiling of a selective 17β-HSD1 inhibitor with sub-nanomolar IC50for a proof-of-principle study

Current endocrine therapeutics for the estrogen-dependent disease endometriosis often lead to considerable side-effects as they act by reducing estrogen action systemically. A more recent approach takes advantage of the fact that the weak estrogen estrone (E1) which is abundant in the plasma, is activated in the target cell to the highly estrogenic estradiol (E2) by 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). 17β-HSD1 is overexpressed in endometriosis and thus a promising target for the treatment of this disease, with the prospect of less target-associated side-effects. Potent inhibitors from the class of bicyclic substituted hydroxyphenylmethanones with sulfonamide moiety recently described by us suffered from high molecular weight and low selectivity over 17βHSD2, the physiological adversary of 17β-HSD1. We describe the structural optimizations leading to the discovery of (5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl)(2,6-difluoro-3-hydroxyphenyl)methanone 20, which displayed a sub-nanomolar IC50towards 17β-HSD1 as well as high selectivity over the type 2 enzyme, the estrogen receptors α and β and a range of hepatic CYP enzymes. The compound did neither show cellular toxicity, nor PXR activation nor mutagenicity in the AMES II assay. Additional favourable pharmacokinetic properties (rat) make 20 a suitable candidate for proof-of-principle studies using xenotransplanted immunodeficient rats.

Towards the evaluation in an animal disease model: Fluorinated 17β-HSD1 inhibitors showing strong activity towards both the human and the rat enzyme

17β-Estradiol (E2), the most potent human estrogen, is known to be involved in the etiology of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the last step of E2 biosynthesis and is thus a promising target for the treatment of EDD. The previously described bicyclic substituted hydroxyphenylmethanones (BSHs) display high inhibitory potency towards human 17β-HSD1, but marginal activity towards rodent 17β-HSD1, precluding a proof of principle study in an animal endometriosis model. The aim of this work was to perform structural optimizations in the BSHs class to enhance inhibitory activity against rodent (mouse and rat) 17β-HSD1 while maintaining activity against the human enzyme. The introduction of fluorine atoms on the benzoyl moiety resulted in compounds with the desired properties. Molecular docking and homology modeling were applied to elucidate the binding mode and interspecies differences in activity. Compound 33 is the most potent inhibitor of both human and rat 17β-HSD1 up to date (IC50 = 2 nM and 97 nM, respectively).

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

Estradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-hydroxysteroid d

SELECTIVE 17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS

The invention relates to selective, non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) inhibitors their production and use, especially for the treatment and/or prophylaxis of hormone-related diseases.

Bicyclic substituted hydroxyphenylmethanones as novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases

Estradiol (E2), the most important estrogen in humans, is involved in the initiation and progression of estrogen-dependent diseases such as breast cancer and endometriosis. Its local production in the target cell is regulated by 17β-hydroxysteroid dehydro