methyl 3-{(E)-2-[2-chloro-4-(5-isopropyl-3-naphthalen-2-ylisoxazol-4-ylmethoxy)phenyl]vinyl}benzoate | 933799-52-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: methyl 3-{(E)-2-[2-chloro-4-(5-isopropyl-3-naphthalen-2-ylisoxazol-4-ylmethoxy)phenyl]vinyl}benzoate
• CAS: 933799-52-1
• 化学式: C₃₃H₂₈ClNO₄
• 分子量: 538.043
• InChiKey: CASPXYDDCLWNPS-VAWYXSNFSA-N

物化性质

• 沸点：
  714.6±60.0 °C(predicted)
• 密度：
  1.243±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.81
• 重原子数：
  39.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 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-[2-chloro-4-(5-isopropyl-3-naphthalen-2-ylisoxazol-4-ylmethoxy)phenyl]vinyl}benzoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-[(E)-2-[2-chloro-4-[(3-naphthalen-2-yl-5-propan-2-yl-1,2-oxazol-4-yl)methoxy]phenyl]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：

  methyl 5-isopropyl-3-naphthalen-2-ylisoxazole-4-carboxylate 在 四溴化碳 、 sodium hydride 、 二异丁基氢化铝 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 methyl 3-{(E)-2-[2-chloro-4-(5-isopropyl-3-naphthalen-2-ylisoxazol-4-ylmethoxy)phenyl]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