(Z)-(2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylene)-tetrahydrofuran-2-yl)methyl 2-propylpentanoate | 1056462-36-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (Z)-(2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylene)-tetrahydrofuran-2-yl)methyl 2-propylpentanoate
• 英文别名: [(4Z)-2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylidene)oxolan-2-yl]methyl 2-propylpentanoate
• CAS: 1056462-36-2
• 化学式: C₂₀H₂₇NO₅
• 分子量: 361.438
• InChiKey: AQBGEPKQGPTWMX-WJDWOHSUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  85.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 生成 (Z)-(2-(hydroxymethyl)-5-oxo-4-(pyridin-2-ylmethylene)-tetrahydrofuran-2-yl)methyl 2-propylpentanoate
  参考文献：
  名称：

  Conformationally Constrained Analogues of Diacylglycerol. 30. An Investigation of Diacylglycerol-lactones Containing Heteroaryl Groups Reveals Compounds with High Selectivity for Ras Guanyl Nucleotide-Releasing Proteins

  摘要：

  Using a diacylglycerol-lactone (DAG-lactone) template previously developed in our laboratory as a scaffold with high binding affinity for C I domains, we describe herein a series of novel DAG-lactones containing heterocyclic moieties (pyridines, quinolines, and indoles) as alpha-arylidene fragments. Some of the DAG-lactones obtained show selective binding to RasGRP3 as compared to PKC alpha by more than 2 orders of magnitude and possess subnanomolar affinities. Because activated C1 domains bound to their ligands (DAG or DAG-lactones) insert into membranes, the lipid composition of membranes (cellular, nuclear, and those of internal organelles) is an important determinant for specificity. Therefore, reaching a proper hydrophilic/lipophilic balance for these molecules is critical. This was achieved by carefully selecting partnering acyl fragments for the DAG-lactones with the appropriate lipophilicity. The results clearly show that the combination of chemical and physical properties in these molecules needs to be perfectly balanced to achieve the desired specificity.

  DOI：

  10.1021/jm800380b