ethyl (2S)-3-(2,4-dichlorophenyl)-2-[[1-(2,4-dichlorophenyl)cyclopropanecarbonyl]amino]propanoate | 1239707-72-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl (2S)-3-(2,4-dichlorophenyl)-2-[[1-(2,4-dichlorophenyl)cyclopropanecarbonyl]amino]propanoate
• CAS: 1239707-72-2
• 化学式: C₂₁H₁₉Cl₄NO₃
• 分子量: 475.199
• InChiKey: CIRNNEDFSYUYNV-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (2S)-3-(2,4-dichlorophenyl)-2-[[1-(2,4-dichlorophenyl)cyclopropanecarbonyl]amino]propanoate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 18.0h， 生成 (S)-3-(2,4-dichlorophenyl)-2-(1-(2,4-dichlorophenyl)cyclopropanecarboxamido)propanoic acid
  参考文献：
  名称：

  Discovery and Characterization of an Inhibitor of Glucosylceramide Synthase

  摘要：

  Targeting glycosphingolipid synthesis has emerged as a novel approach for treating metabolic diseases. 32 (EXEL-0346) represents a new class of glucosylceramide synthase (GCS) inhibitors. This report details the elaboration of hit 8 with the goal of achieving and maintaining maximum GCS inhibition in vivo. 32 inhibited GCS with an IC50 of 2 nM and achieved maximum hepatic GCS inhibition after four or five daily doses in rodents. Robust improvements in glucose tolerance in DIO mice and ZDF rats were observed after 2 weeks of q.d. dosing. Four weeks of dosing resulted in decreased plasma triglycerides and reduced hepatic fat deposition. Thus, 32 provides insight into the amount of metabolic regulation that can be restored following achievement of maximal target knockdown.

  DOI：

  10.1021/jm300122u
• 作为产物：
  描述：

  ethyl (2S)-2-(tert-butoxycarbonylamino)-3-(2,4-dichlorophenyl)propanoate 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 19.0h， 生成 ethyl (2S)-3-(2,4-dichlorophenyl)-2-[[1-(2,4-dichlorophenyl)cyclopropanecarbonyl]amino]propanoate
  参考文献：
  名称：

  Discovery and Characterization of an Inhibitor of Glucosylceramide Synthase

  摘要：

  Targeting glycosphingolipid synthesis has emerged as a novel approach for treating metabolic diseases. 32 (EXEL-0346) represents a new class of glucosylceramide synthase (GCS) inhibitors. This report details the elaboration of hit 8 with the goal of achieving and maintaining maximum GCS inhibition in vivo. 32 inhibited GCS with an IC50 of 2 nM and achieved maximum hepatic GCS inhibition after four or five daily doses in rodents. Robust improvements in glucose tolerance in DIO mice and ZDF rats were observed after 2 weeks of q.d. dosing. Four weeks of dosing resulted in decreased plasma triglycerides and reduced hepatic fat deposition. Thus, 32 provides insight into the amount of metabolic regulation that can be restored following achievement of maximal target knockdown.

  DOI：

  10.1021/jm300122u