2-Bromaethyl-p-trifluormethylbenzhydrylaether | 846-91-3

• 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: 2-Bromaethyl-p-trifluormethylbenzhydrylaether
• 英文别名: 1-((2-bromoethoxy)(phenyl)methyl)-4-(trifluoromethyl)benzene
• CAS: 846-91-3
• 化学式: C₁₆H₁₄BrF₃O
• 分子量: 359.186
• InChiKey: JHCXSGYAPAJNSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.21
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  2-Bromaethyl-p-trifluormethylbenzhydrylaether 在 哌啶 、 sodium tetrahydroborate 、 cobalt dimethylglyoxime 、 potassium carbonate 、 苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 29.0h， 生成 5-(4-(2-(phenyl(4-(trifluoromethyl)phenyl)methoxy)ethoxy)benzyl) thiazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

  摘要：

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.051
• 作为产物：
  描述：

  4-三氟甲基-二苯甲醇 、 2-溴乙醇 在 硫酸 作用下， 以 甲苯 为溶剂， 反应 3.5h， 以89%的产率得到2-Bromaethyl-p-trifluormethylbenzhydrylaether
  参考文献：
  名称：

  Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

  摘要：

  Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-gamma (PPAR-gamma) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.051