methyl 3-((E)-2-{4-[5-tert-butyl-3-(2,6-dichlorophenyl)isoxazol-4-ylmethoxy]-2-chlorophenyl}vinyl)benzoate | 933799-56-5

• 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: methyl 3-((E)-2-{4-[5-tert-butyl-3-(2,6-dichlorophenyl)isoxazol-4-ylmethoxy]-2-chlorophenyl}vinyl)benzoate
• 英文别名: Methyl 3-[(1E)-2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1,1-dimethylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoate；methyl 3-[(E)-2-[4-[[5-tert-butyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-2-chlorophenyl]ethenyl]benzoate
• CAS: 933799-56-5
• 化学式: C₃₀H₂₆Cl₃NO₄
• 分子量: 570.9
• InChiKey: XSVKZLHTJHVLIB-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.14
• 重原子数：
  38.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  61.56
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 3-((E)-2-{4-[5-tert-butyl-3-(2,6-dichlorophenyl)isoxazol-4-ylmethoxy]-2-chlorophenyl}vinyl)benzoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-[(E)-2-(4-{[5-tert-butyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}-2-chlorophenyl)ethenyl]benzoic acid
  参考文献：
  名称：

  Design, synthesis, and evaluation of non-steroidal farnesoid X receptor (FXR) antagonist

  摘要：

  A series of substituted-isoxazole derivatives was prepared as candidate farnesoid X receptor (FXR) antagonists, based on our previously proposed ligand superfamily concept. Structure-activity relationship studies indicated that the shape and the structural bulkiness of the substituent at the 5-position of the isoxazole ring affected FXR-antagonistic activity. Compounds 15g (5-substituent: 2-naphthyl) and 15h (5-substituent: 4-biphenyl) were identified as potent antagonists with higher selectivity for FXR over progesterone receptor than the naturally occurring FXR antagonist GS. The 5-substituent is also a critical determinant of the characteristic corepressor recruitment profile of this class of FXR antagonists, though distinct mechanisms appear to be involved: 15h stabilizes the corepressor-nuclear receptor interaction, while 15g inhibits coactivator recruitment. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.046
• 作为产物：
  描述：

  2,6-dichlorobenzohydroximoyl chloride 在 四溴化碳 、 sodium methylate 、 sodium hydride 、 二异丁基氢化铝 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 3-((E)-2-{4-[5-tert-butyl-3-(2,6-dichlorophenyl)isoxazol-4-ylmethoxy]-2-chlorophenyl}vinyl)benzoate
  参考文献：
  名称：

  Design, synthesis, and evaluation of non-steroidal farnesoid X receptor (FXR) antagonist

  摘要：

  A series of substituted-isoxazole derivatives was prepared as candidate farnesoid X receptor (FXR) antagonists, based on our previously proposed ligand superfamily concept. Structure-activity relationship studies indicated that the shape and the structural bulkiness of the substituent at the 5-position of the isoxazole ring affected FXR-antagonistic activity. Compounds 15g (5-substituent: 2-naphthyl) and 15h (5-substituent: 4-biphenyl) were identified as potent antagonists with higher selectivity for FXR over progesterone receptor than the naturally occurring FXR antagonist GS. The 5-substituent is also a critical determinant of the characteristic corepressor recruitment profile of this class of FXR antagonists, though distinct mechanisms appear to be involved: 15h stabilizes the corepressor-nuclear receptor interaction, while 15g inhibits coactivator recruitment. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.046