C10d | 1434927-54-4

• 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: C10d
• 英文别名: N-(3-(1H-imidazol-1-yl)propyl)-1-(4-fluorophenyl)-2,2-dimethylcyclopropane-1-carboxamide；1-(4-fluorophenyl)-N-(3-imidazol-1-ylpropyl)-2,2-dimethylcyclopropane-1-carboxamide
• CAS: 1434927-54-4
• 化学式: C₁₈H₂₂FN₃O
• 分子量: 315.391
• InChiKey: MBTXJGAIMKPLBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(3-氨基丙基)咪唑 、 1-(4-氟苯基)-2,2-二甲基环丙烷羧酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 生成 C10d
  参考文献：
  名称：

  Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator

  摘要：

  Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity. The compound C10d was also tested in vivo for its lipid lowering activity. Mice were fed a high-fat diet (HFD) for four months, and treated for one week at 10 mg/kg. At this dose, C10d exhibited in vivo biological activity as indicated by lower TG and cholesterol levels as well as reduced body fat content as determined by ECHO-MRI. Furthermore, C10d also reduced the HFD induced fat accumulation in the liver. Our study has provided insights into the structural and functional characteristics of this novel LPL activator. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.11.053

文献信息

• Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator
  作者：Werner J. Geldenhuys、Joel Caporoso、Thomas C. Leeper、Yoon-Kwang Lee、Li Lin、Altaf S. Darvesh、Prabodh Sadana

  DOI：10.1016/j.bmcl.2016.11.053

  日期：2017.1

  Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity. The compound C10d was also tested in vivo for its lipid lowering activity. Mice were fed a high-fat diet (HFD) for four months, and treated for one week at 10 mg/kg. At this dose, C10d exhibited in vivo biological activity as indicated by lower TG and cholesterol levels as well as reduced body fat content as determined by ECHO-MRI. Furthermore, C10d also reduced the HFD induced fat accumulation in the liver. Our study has provided insights into the structural and functional characteristics of this novel LPL activator. (C) 2016 Elsevier Ltd. All rights reserved.