7-N,N-diethylamino-3-(3-phenyl-1,2,4-oxadiazol-5-yl)coumarin | 892754-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-N,N-diethylamino-3-(3-phenyl-1,2,4-oxadiazol-5-yl)coumarin
• 英文别名: 7-(diethylamino)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)-2H-chromen-2-one；7-(diethylamino)-3-(3-phenyl-1,2,4-oxadiazol-5-yl)chromen-2-one
• CAS: 892754-02-8
• 化学式: C₂₁H₁₉N₃O₃
• mdl: MFCD14901776
• 分子量: 361.4
• InChiKey: JGGYVUDYCGHHIK-UHFFFAOYSA-N

物化性质

• 沸点：
  586.7±60.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  68.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(二乙氨基)水杨醛 在 哌啶 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.33h， 生成 7-N,N-diethylamino-3-(3-phenyl-1,2,4-oxadiazol-5-yl)coumarin
  参考文献：
  名称：

  Fragmentation of GW4064 led to a highly potent partial farnesoid X receptor agonist with improved drug-like properties

  摘要：

  The ligand activated transcription factor farnesoid X receptor (FXR) is a crucial regulator of several metabolic and inflammatory pathways and its activation by agonistic ligands seems a valuable therapeutic approach for many disorders. Most known non-steroidal FXR agonists however, have limitations that hinder their clinical development and novel FXR ligands are required. Evaluation of the co-crystal structures of the widely used FXR agonist GW4064 and related compounds in complex with the FXR ligand binding domain indicated that their disubstituted isoxazole moiety is especially relevant for FXR activation. By investigation of GW4064-fragments missing the aromatic tail, we discovered a highly potent and soluble partial FXR agonist (14, ST-1892) as well as a fluorescent FXR ligand (15) as potential pharmacological tool. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.035

文献信息

• Isomeric 3-Isoxadiazolylcoumarins and Their Derivatives
  作者：Oleksandr S. Detistov、Valeriy D. Orlov、Irina O. Zhuravel'

  DOI：10.1002/jhet.893

  日期：2012.7

  Here, we represent preparative methods of synthesis of isomeric 3‐isoxadiazolylcoumarins and their derivatives. Two new synthetic methods have been developed for 3‐[1,2,4‐oxadiazol‐5‐yl]coumarins I. The first method is based on a three‐component condensation of coumarin‐;3‐carboxylic acids, 1,1′‐carbonyldiimidazole, and amidoximes. The second method essentially uses the interaction of 5‐cyanomethyl‐1

  在这里，我们代表了异构体3-异二唑基香豆素及其衍生物的合成制备方法。对于3- [1,2,4-恶二唑-5-基]香豆素I，已经开发出两种新的合成方法。第一种方法基于香豆素-; 3-羧酸，1,1'-羰基二咪唑和a胺肟的三组分缩合。第二种方法本质上是利用5-氰基甲基1,2,4-恶二唑与水杨醛的相互作用。已经制定了制备3- [1,2,4-恶二唑-3-基]香豆素II的一般方法。此外，上述合成方法为2-亚同价衍生物III和IV的合成开辟了道路。 之前没有描述，通过亚氨基2-亚氨基与许多氨基化合物的亲核取代反应使这些化合物多样化。
• Fragmentation of GW4064 led to a highly potent partial farnesoid X receptor agonist with improved drug-like properties
  作者：Daniel Flesch、Matthias Gabler、Andreas Lill、Roberto Carrasco Gomez、Ramona Steri、Gisbert Schneider、Holger Stark、Manfred Schubert-Zsilavecz、Daniel Merk

  DOI：10.1016/j.bmc.2015.04.035

  日期：2015.7

  The ligand activated transcription factor farnesoid X receptor (FXR) is a crucial regulator of several metabolic and inflammatory pathways and its activation by agonistic ligands seems a valuable therapeutic approach for many disorders. Most known non-steroidal FXR agonists however, have limitations that hinder their clinical development and novel FXR ligands are required. Evaluation of the co-crystal structures of the widely used FXR agonist GW4064 and related compounds in complex with the FXR ligand binding domain indicated that their disubstituted isoxazole moiety is especially relevant for FXR activation. By investigation of GW4064-fragments missing the aromatic tail, we discovered a highly potent and soluble partial FXR agonist (14, ST-1892) as well as a fluorescent FXR ligand (15) as potential pharmacological tool. (C) 2015 Elsevier Ltd. All rights reserved.