methyl 3-({2-chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylmethoxy]benzoyl}(n-propyl)amino)benzoate | 933799-80-5

• 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-({2-chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylmethoxy]benzoyl}(n-propyl)amino)benzoate
• 英文别名: Methyl 3-[[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]benzoyl]-propylamino]benzoate
• CAS: 933799-80-5
• 化学式: C₃₁H₂₉Cl₃N₂O₅
• 分子量: 615.941
• InChiKey: WXVDUWRWCSZHIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-({2-chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylmethoxy]benzoyl}(n-propyl)amino)benzoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 Isoxazole derivative, 15c
  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：

  3-氨基苯甲酸甲酯 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 3-({2-chloro-4-[3-(2,6-dichlorophenyl)-5-isopropylisoxazol-4-ylmethoxy]benzoyl}(n-propyl)amino)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

文献信息

• Design, synthesis, and evaluation of non-steroidal farnesoid X receptor (FXR) antagonist
  作者：Masahiko Kainuma、Makoto Makishima、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmc.2007.01.046

  日期：2007.4

  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.