N-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)benzyl)-6-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-N-methyl-2-(trifluoromethyl)pyridin-3-amine | 1245613-91-5

• 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: N-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)benzyl)-6-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-N-methyl-2-(trifluoromethyl)pyridin-3-amine
• CAS: 1245613-91-5
• 化学式: C₃₅H₄₂Cl₂F₃N₃O₄Si
• 分子量: 724.723
• InChiKey: XHLYKLYORJTRJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  48.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  69.85
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)benzyl)-6-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-N-methyl-2-(trifluoromethyl)pyridin-3-amine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以75%的产率得到2-(4-(((6-((3-(2,6-Dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-2-(trifluoromethyl)pyridin-3-yl)(methyl)amino)methyl)phenoxy)ethanol
  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：

  聚合甲醛 、 N-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)benzyl)-6-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-2-(trifluoromethyl)pyridin-3-amine 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 1,1-二氯乙烷 为溶剂， 反应 24.0h， 生成 N-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)benzyl)-6-((3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-yl)methoxy)-N-methyl-2-(trifluoromethyl)pyridin-3-amine
  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