8-cyano-6-methoxy-2-naphthyl trifluoromethanesulfonate | 858946-73-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 8-cyano-6-methoxy-2-naphthyl trifluoromethanesulfonate
• 英文别名: 8-cyano-6-methoxynaphthalene-2-yl trifluoromethanesulfonate；(8-cyano-6-methoxynaphthalen-2-yl) trifluoromethanesulfonate
• CAS: 858946-73-3
• 化学式: C₁₃H₈F₃NO₄S
• 分子量: 331.272
• InChiKey: SMDQJJWDUBUEAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  84.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-cyano-6-methoxy-2-naphthyl trifluoromethanesulfonate 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 四(三苯基膦)钯 、 溴 、 sodium carbonate 、 溶剂黄146 、 锌 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-(3-fluoro-4-methoxyphenyl)-2-methoxynaphthalene-1,4-dicarbonitrile
  参考文献：
  名称：

  ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity

  摘要：

  The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.

  DOI：

  10.1021/jm058173s
• 作为产物：
  描述：

  7-羟基-1-萘甲腈 在 吡啶 、 溴 、 溶剂黄146 、 copper(I) bromide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 8-cyano-6-methoxy-2-naphthyl trifluoromethanesulfonate
  参考文献：
  名称：

  ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity

  摘要：

  The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.

  DOI：

  10.1021/jm058173s

文献信息

• Substituted 6-Phenyl-2-naphthols. Potent and Selective Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Design, Synthesis, Biological Evaluation, and Pharmacokinetics
  作者：Sandrine Marchais-Oberwinkler、Patricia Kruchten、Martin Frotscher、Erika Ziegler、Alexander Neugebauer、Umadevi Bhoga、Emmanuel Bey、Ursula Müller-Vieira、Josef Messinger、Hubert Thole、Rolf W. Hartmann

  DOI：10.1021/jm800367k

  日期：2008.8.1

  concentration is mainly regulated by 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which catalyzes the reduction of the weak estrogen estrone (E1) to the highly potent E2. This enzyme is thus an important target for the treatment of hormone-dependent diseases. Thirty-seven novel substituted 6-phenyl-2-naphthols were synthesized and evaluated for 17beta-HSD1 inhibition, selectivity toward 17beta-HSD2

  17β-雌二醇（E2）与雌激素依赖性疾病的发生和发展有关。它的浓度主要受17beta-羟类固醇脱氢酶1型（17beta-HSD1）调节，该酶催化将弱雌激素雌酮（E1）还原为强效E2。因此，该酶是治疗激素依赖性疾病的重要靶标。合成了37种新型取代的6-苯基-2-萘酚，并评估了其对17beta-HSD1的抑制作用，对17beta-HSD2和雌激素受体（ER）α和β的选择性以及药代动力学特性。SAR研究表明，这些化合物最有可能根据结合模式B与活性位点结合，即与类固醇A环类似的6-苯基部分。虽然苯环上的取代会降低活性，
• 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 type 1 inhibitors for the treatment of hormone-related diseases
  申请人：Hartmann Rolf

  公开号：US08546392B2

  公开（公告）日：2013-10-01

  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及其生产方法。
• 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