N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-4-bromo-2-trifluoromethoxybenzenesulfonamide | 1064681-06-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-4-bromo-2-trifluoromethoxybenzenesulfonamide
• 英文别名: 4-bromo-N-{3-[2-hydroxy-6-(3-hydroxyphenyl)-1-naphthyl]phenyl}-2-(trifluoromethoxy)benzenesulfonamide；4-bromo-N-[3-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]phenyl]-2-(trifluoromethoxy)benzenesulfonamide
• CAS: 1064681-06-6
• 化学式: C₂₉H₁₉BrF₃NO₅S
• 分子量: 630.439
• InChiKey: PBBRVIDXAVIVMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1,6-二溴-2-萘酚 在 吡啶 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 三溴化硼 、 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， -25.0~150.0 ℃ 、150.0 kPa 条件下， 反应 167.25h， 生成 N-(3-(2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl)phenyl)-4-bromo-2-trifluoromethoxybenzenesulfonamide
  参考文献：
  名称：

  Lead Optimization of 17β-HSD1 Inhibitors of the (Hydroxyphenyl)naphthol Sulfonamide Type for the Treatment of Endometriosis

  摘要：

  The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17 beta-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 17 beta-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17 beta-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors a and 9 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.

  DOI：

  10.1021/jm201735j

文献信息

• 17Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Hormone-Related Diseases
  申请人：Hartmann Rolf

  公开号：US20100204234A1

  公开（公告）日：2010-08-12

  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.

  该发明涉及使用非甾体17β-羟基类固醇脱氢酶1抑制剂治疗和预防激素依赖性疾病，特别是雌激素依赖性疾病。该发明还涉及适当的抑制剂以及生产方法。
• 17BETA-HYDROXYSTEROID-DEHYDROGENASE-TYP1-INHIBITOREN ZUR BEHANDLUNG HORMONABHÄNGIGER ERKRANKUNGEN
  申请人：Universität des Saarlandes

  公开号：EP2131826A2

  公开（公告）日：2009-12-16
• US8546392B2
  申请人：——

  公开号：US8546392B2

  公开（公告）日：2013-10-01
• [DE] 17BETA-HYDROXYSTEROID-DEHYDROGENASE-TYP1-INHIBITOREN ZUR BEHANDLUNG HORMONABHÄNGIGER ERKRANKUNGEN<br/>[EN] 17BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE 1 INHIBITORS FOR THE TREATMENT OF HORMONE-DEPENDENT DISEASES<br/>[FR] INHIBITEURS DE 17BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1 UTILISÉS POUR TRAITER DES MALADIES HORMONO-DÉPENDANTES
  申请人：UNIV SAARLAND

  公开号：WO2008116920A2

  公开（公告）日：2008-10-02

  [EN] 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.
  [FR] La présente invention concerne l'utilisation d'inhibiteurs de 17bêta-hydroxystéroïde déshydrogénase de type 1 non stéroïdiens pour traiter et prévenir des maladies hormono-dépendantes, en particulier des maladies oestrogéno-dépendantes. Cette invention concerne également des inhibiteurs adaptés et un procédé de production correspondant.
  [DE] Die Erfindung betrifft die Verwendung von nicht-steroidalen 17Beta-Hydroxysteroid-Dehydrogenase Typ1 Inhibitoren zur Behandlung und Prophylaxe hormonabhängiger, insbesondere estrogenabhängiger Erkrankungen. Weiterhin werden geeignete Inhibitoren sowie ein Verfahren zu deren Herstellung zur Verfügung gestellt.
• Lead Optimization of 17β-HSD1 Inhibitors of the (Hydroxyphenyl)naphthol Sulfonamide Type for the Treatment of Endometriosis
  作者：Claudia Henn、Almuth Einspanier、Sandrine Marchais-Oberwinkler、Martin Frotscher、Rolf W. Hartmann

  DOI：10.1021/jm201735j

  日期：2012.4.12

  The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17 beta-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 17 beta-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17 beta-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors a and 9 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.