3-(3-氟-4-羟基苯基)-7-羟基萘-1-甲腈 | 550997-55-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 3-(3-氟-4-羟基苯基)-7-羟基萘-1-甲腈
• 英文名称: WAY-202196
• 英文别名: 3-(3-fluoro-4-hydroxy-phenyl)-7-hydroxy-naphthalene-1-carbonitrile；3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile；3-(3-fluoro-4-hydroxyphenyl)-7-hydroxynaphthalene-1-carbonitrile
• CAS: 550997-55-2
• 化学式: C₁₇H₁₀FNO₂
• 分子量: 279.27
• InChiKey: NSSOSHDCWCMNDM-UHFFFAOYSA-N

物化性质

• 沸点：
  497.0±45.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  | 2-8℃ |

制备方法与用途

生物活性

ERB-196 是一个非类固醇选择性雌激素受体-β (ERβ) 激动剂。

靶点

• ERβ

体内研究

ERB-196 显著减少了胃肠道黏膜表面的病理损伤证据（0.7±0.1 vs. 2.3±0.2 对照，p<0.05）。小肠黏膜段（10厘米）的黏膜质量在 ERB-196 治疗下得到了更好的保存（63±20 [ERB-196] 对比对照治疗的 31±24），但这一差异未达到统计学显著性（p<0.06）。ERB-196 在预防致死性方面表现出高度有效性。与对照溶剂组相比，ERB-196 显著提高了生存率，符合中性粒细胞减少症模型的预期结果。

反应信息

• 作为反应物：
  描述：

  3-(3-氟-4-羟基苯基)-7-羟基萘-1-甲腈 在 咪唑 、 正丁基锂 、 二异丁基氢化铝 、 三苯基膦 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 3.17h， 生成 7-(tert-Butyl-dimethyl-silanyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-3-fluoro-phenyl]-1-ethynyl-naphthalene
  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：

  3-(3-fluoro-4-methoxyphenyl)-7-methoxy-1-naphthonitrile 在 三溴化硼 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 4.33h， 以96%的产率得到3-(3-氟-4-羟基苯基)-7-羟基萘-1-甲腈
  参考文献：
  名称：

  Process for the synthesis of 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxynaphthonitrile

  摘要：

  一种制备公式I化合物及其中间体化合物的方法，其中R1为CN、F或Cl；R2为H或Br；R3和R4分别独立地为H或F。公式I化合物在治疗慢性炎症性疾病，如类风湿性关节炎方面具有用途。

  公开号：

  US20050054870A1

文献信息

• Substituted phenyl naphthalenes as estrogenic agents
  申请人：Wyeth

  公开号：US20030181519A1

  公开（公告）日：2003-09-25

  This invention provides estrogen receptor modulators of formula I, having the structure 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 , are as defined in the specification, or a pharmaceutically acceptable salt thereof.

  这项发明提供了具有结构的式I的雌激素受体调节剂 1 其中 R 1 ，R 2 ，R 3 ，R 4 ，R 5 ，R 6 ，R 7 ，R 8 ，R 9 和R 10 如规范中所定义，或其药用可接受盐。
• PHARMACEUTICAL COMPOSITIONS AND METHODS OF PREVENTING, TREATING, OR INHIBITING INFLAMMATORY DISEASES, DISORDERS, OR CONDITIONS OF THE SKIN, AND DISEASES, DISORDERS, OR CONDITIONS ASSOCIATED WITH COLLAGEN DEPLETION
  申请人：CHANG Chien-Neng

  公开号：US20090010884A1

  公开（公告）日：2009-01-08

  The present invention provides compositions and methods for preventing, treating, or inhibiting inflammatory diseases, disorders, or conditions of the skin, and diseases, disorders, or conditions associated with collagen depletion using one or more estrogenic agents.

  本发明提供了使用一个或多个雌激素类药物预防、治疗或抑制皮肤炎症性疾病、紊乱或状况以及与胶原蛋白流失相关的疾病、紊乱或状况的组合物和方法。
• MONO-AND-DI-PHOSPHATES OF 3-(3-FLUORO-4-HYDROXY-PHENYL)-7-HYDROXY-NAPHTHALENE-1-CARBONITRILE
  申请人：FAWZI Mahdi B.

  公开号：US20080214507A1

  公开（公告）日：2008-09-04

  Compounds of formula II wherein each R 1 and R 2 is independently selected from H and —P(O)(R 3 )(R 4 ), provided that at least one of R 1 and R 2 is —P(O)(R 3 )(R 4 ); each R 3 and R 4 is independently selected from the group consisting of H, —OH, C 1 -C 6 alkyl and C 1 -C 6 alkoxy; or a pharmaceutically acceptable salt thereof. Pharmaceutical compositions comprising a compound of formula II, and methods of administering such compounds and compositions.

  II式化合物，其中每个R1和R2分别选自H和—P(O)(R3)(R4)，前提是至少一个R1和R2是—P(O)(R3)(R4)；每个R3和R4分别选自H、—OH、C1-C6烷基和C1-C6烷氧基；或其药学上可接受的盐。包括II式化合物的药物组合物，以及给予此类化合物和组合物的方法。
• Antiarthritic combinations
  申请人：Wyeth

  公开号：US20040248865A1

  公开（公告）日：2004-12-09

  This invention provides combinations of an ER&bgr; selective ligand with an anti-arthritis agent, which are useful in the treatment or inhibition of arthritis.

  本发明提供了ER&bgr; 选择性配体与抗关节炎药物的组合，可用于治疗或抑制关节炎。
• Novel uses for estrogen beta agonists
  申请人：Day Mark

  公开号：US20060135574A1

  公开（公告）日：2006-06-22

  This invention provides methods for treating cognitive diseases or disorders and symptoms thereof with estrogen beta selective agonists.

  本发明提供了利用雌激素 beta 选择性激动剂治疗认知疾病或紊乱及其症状的方法。