2,4-二甲氧基苯基[(2-氟-3-(三氟甲基)苯基)]甲酮 | 680610-69-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,4-二甲氧基苯基[(2-氟-3-(三氟甲基)苯基)]甲酮
• 英文名称: 2,4-dimethoxyphenyl[(2-fluoro-3-(trifluoromethyl)phenyl)]methanone
• 英文别名: (2,4-Dimethoxyphenyl)[2-fluoro-3-(trifluoromethyl)phenyl]methanone；(2,4-dimethoxyphenyl)-[2-fluoro-3-(trifluoromethyl)phenyl]methanone
• CAS: 680610-69-9
• 化学式: C₁₆H₁₂F₄O₃
• 分子量: 328.263
• InChiKey: DPPVASNKQONCGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,4-二甲氧基苯基[(2-氟-3-(三氟甲基)苯基)]甲酮 在 吡啶 、 肼 作用下， 反应 1.0h， 以94%的产率得到3-(2,4-dimethoxyphenyl)-7-(trifluoromethyl)-1H-indazole
  参考文献：
  名称：

  Development of a Selective Modulator of Aryl Hydrocarbon (Ah) Receptor Activity that Exhibits Anti-Inflammatory Properties

  摘要：

  The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR in normal physiology is still an area of intense investigation. For example, this receptor plays an important role in certain immune responses. We have previously determined that the AHR can mediate repression of acute-phase genes in the liver. For this observation to be therapeutically useful, selective activation of the AHR would likely be necessary. Recently, the selective estrogen receptor ligand WAY-169916 has also been shown to be a selective AHR ligand. WAY-169916 can efficiently repress cytokine-mediated acute-phase gene expression (e.g., SAAI) yet fail to mediate a dioxin response element-driven increase in transcriptional activity. The goals of this study were to structurally modify WAY-169916 to block binding to the estrogen receptor and increase its affinity for the AHR. A number of WAY-169916 derivatives were synthesized and subjected to characterization as AHR ligands. The substitution of a key hydroxy group for a methoxy group ablates binding to the estrogen receptor and increases its affinity for the AHR. The compound 1-allyl-7-trifluoromethyl-1H-indazol-3-yl]-4-methoxyphenol (SGA 360), in particular, exhibited essentially no AHR agonist activity yet was able to repress cytokine-mediated SAAI gene expression in Huh7 cells. SGA 360 was tested in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated ear inflammatory edema model using C57BL6/J and Ahr(-/-) mice. Our findings indicate that SGA 360 significantly inhibits TPA-mediated ear swelling and induction of a number of inflammatory genes (e.g., Saa3, Cox2, and Il6) in C57BL6/J mice. In contrast, SGA 360 had no effect on TPA-mediated ear swelling or inflammatory gene expression in Ahr(-/-) mice. Collectively, these results indicate that SGA 360 is a selective Ah receptor modulator (SAhRM) that exhibits anti-inflammatory properties in vivo.

  DOI：

  10.1021/tx100045h
• 作为产物：
  描述：

  2-氟-3-(三氟甲基)苯甲酸 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 11.0h， 生成 2,4-二甲氧基苯基[(2-氟-3-(三氟甲基)苯基)]甲酮
  参考文献：
  名称：

  Development of a Selective Modulator of Aryl Hydrocarbon (Ah) Receptor Activity that Exhibits Anti-Inflammatory Properties

  摘要：

  The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR in normal physiology is still an area of intense investigation. For example, this receptor plays an important role in certain immune responses. We have previously determined that the AHR can mediate repression of acute-phase genes in the liver. For this observation to be therapeutically useful, selective activation of the AHR would likely be necessary. Recently, the selective estrogen receptor ligand WAY-169916 has also been shown to be a selective AHR ligand. WAY-169916 can efficiently repress cytokine-mediated acute-phase gene expression (e.g., SAAI) yet fail to mediate a dioxin response element-driven increase in transcriptional activity. The goals of this study were to structurally modify WAY-169916 to block binding to the estrogen receptor and increase its affinity for the AHR. A number of WAY-169916 derivatives were synthesized and subjected to characterization as AHR ligands. The substitution of a key hydroxy group for a methoxy group ablates binding to the estrogen receptor and increases its affinity for the AHR. The compound 1-allyl-7-trifluoromethyl-1H-indazol-3-yl]-4-methoxyphenol (SGA 360), in particular, exhibited essentially no AHR agonist activity yet was able to repress cytokine-mediated SAAI gene expression in Huh7 cells. SGA 360 was tested in a 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated ear inflammatory edema model using C57BL6/J and Ahr(-/-) mice. Our findings indicate that SGA 360 significantly inhibits TPA-mediated ear swelling and induction of a number of inflammatory genes (e.g., Saa3, Cox2, and Il6) in C57BL6/J mice. In contrast, SGA 360 had no effect on TPA-mediated ear swelling or inflammatory gene expression in Ahr(-/-) mice. Collectively, these results indicate that SGA 360 is a selective Ah receptor modulator (SAhRM) that exhibits anti-inflammatory properties in vivo.

  DOI：

  10.1021/tx100045h

文献信息

• [EN] SUBSTITUTED 4-(INDAZOL-3-YL)PHENOLS AS ESTROGEN RECEPTOR (ER) LIGANDS AND THEIR USE IN THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] 4-(INDAZOL-3-YL)PHENOLS SUBSTITUES COMME LIGANDS DU RECEPTEUR DES OESTROGENES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：WYETH CORP

  公开号：WO2004031159A1

  公开（公告）日：2004-04-15

  This invention provides compound of formulae I or II having the structure wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined in the specification or a pharmaceutically acceptable salt thereof which are useful for the treatment of the inflammatory component of diseases and are particularly useful in treating atherosclerosis, myocardial infarction, congestive heart failure, inflammatory bowel disease. Arthritis, type II diabetes, and autoimmune diseases such as multiple sclerosis and rheumatiod arthritis.

  这项发明提供了具有结构的化合物I或II的公式，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10如规范中定义，或其药用盐，这些化合物对治疗疾病的炎症成分有用，特别适用于治疗动脉粥样硬化、心肌梗死、充血性心力衰竭、炎症性肠病、关节炎、2型糖尿病以及多发性硬化和类风湿关节炎等自身免疫疾病。
• Indazoles useful in treating cardiovascular diseases
  申请人：Steffan J. Robert

  公开号：US20060030612A1

  公开（公告）日：2006-02-09

  This invention provides compounds of Formula (I) or (Ia): that are useful in the treatment or inhibition of LXR mediated diseases.

  这项发明提供了I式或Ia式化合物：它们可用于治疗或抑制LXR介导的疾病。
• Substituted 4-(indazol-3-yl)phenols
  申请人：Wyeth

  公开号：US20040167127A1

  公开（公告）日：2004-08-26

  This invention provides compound of formulae I or II 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 which are useful for the treatment of the inflammatory component of diseases and are particularly useful in treating atherosclerosis, myocardial infarction, congestive heart failure, inflammatory bowel disease, arthritis, type II diabetes, and autoimmune diseases such as multiple sclerosis and rheumatiod arthritis.

  本发明提供了式I或式II的化合物，其结构为1，其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10如规范中所定义，或其药学上可接受的盐，其对于疾病的炎症成分具有治疗作用，尤其是在治疗动脉粥样硬化、心肌梗死、充血性心力衰竭、炎症性肠病、关节炎、2型糖尿病以及自身免疫性疾病如多发性硬化和类风湿性关节炎方面特别有用。
• Substituted 4-(Indazol-3-yl)phenols
  申请人：Steffan J. Robert

  公开号：US20070225349A1

  公开（公告）日：2007-09-27

  This invention provides compound of formulae I or II having the structure 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 which are useful for the treatment of the inflammatory component of diseases and are particularly useful in treating atherosclerosis, myocardial infarction, congestive heart failure, inflammatory bowel disease, arthritis, type II diabetes, and autoimmune diseases such as multiple sclerosis and rheumatiod arthritis.

  该发明提供了式I或II的化合物，其结构为： 其中R1、R2、R3、R4、R5、R6、R7、R8、R9和R10如规范中所定义，或其药学上可接受的盐，用于治疗疾病的炎症成分，特别适用于治疗动脉硬化、心肌梗塞、充血性心力衰竭、炎症性肠病、关节炎、II型糖尿病以及多发性硬化和风湿性关节炎等自身免疫疾病。
• Indazoles
  申请人：Wyeth

  公开号：US07592363B2

  公开（公告）日：2009-09-22

  This invention provides compounds of Formula (I) or (Ia): that are useful in the treatment or inhibition of LXR mediated diseases.

  该发明提供了公式(I)或(Ia)的化合物：它们在治疗或抑制LXR介导的疾病方面是有用的。