4-(((5-(1-chloroethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole | 1245614-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(((5-(1-chloroethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole
• CAS: 1245614-19-0
• 化学式: C₂₁H₁₆Cl₃F₃N₂O₂
• 分子量: 491.724
• InChiKey: JBHANCJKMBIZFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.82
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.15
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(((5-(1-chloroethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole 、 对羟基苯甲酸甲酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 methyl 4-(1-(6-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)-2-(trifluoromethyl)pyridin-3-yl)ethoxy)benzoate
  参考文献：
  名称：

  Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists

  摘要：

  To overcome the known liabilities of GW4064 a series of analogs were synthesized where the stilbene double bond is replaced by an oxymethylene or amino-methylene linker connecting a terminal benzoic acid with a substituted heteroaryl in the middle ring position. As a result we discovered compounds with increased potency in vitro that cause dose-dependent reduction of plasma triglycerides and cholesterol in db/db mice down to 2 x 1 mg/kg/day upon oral administration. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.084
• 作为产物：
  描述：

  1-(6-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)-2-(trifluoromethyl)pyridin-3-yl)ethan-1-ol 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以92%的产率得到4-(((5-(1-chloroethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)methyl)-5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazole
  参考文献：
  名称：

  Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists

  摘要：

  To overcome the known liabilities of GW4064 a series of analogs were synthesized where the stilbene double bond is replaced by an oxymethylene or amino-methylene linker connecting a terminal benzoic acid with a substituted heteroaryl in the middle ring position. As a result we discovered compounds with increased potency in vitro that cause dose-dependent reduction of plasma triglycerides and cholesterol in db/db mice down to 2 x 1 mg/kg/day upon oral administration. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.084