(E)-(4-(benzo[b]thiophen-3-ylmethylene)-2-(hydroxymethyl)-5-oxotetrahydrofuran-2-yl)methyl pivalate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: (E)-(4-(benzo[b]thiophen-3-ylmethylene)-2-(hydroxymethyl)-5-oxotetrahydrofuran-2-yl)methyl pivalate
• 英文别名: [(4E)-4-(1-benzothiophen-3-ylmethylidene)-2-(hydroxymethyl)-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₂₀H₂₂O₅S
• 分子量: 374.458
• InChiKey: XELZELDAOXMYOD-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-bis<<(tert-butyldiphenylsilyl)oxy>methyl>tetrahydro-2-furanone 在 吡啶 、 四丁基氟化铵 、 甲基磺酰氯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (E)-(4-(benzo[b]thiophen-3-ylmethylene)-2-(hydroxymethyl)-5-oxotetrahydrofuran-2-yl)methyl pivalate
  参考文献：
  名称：

  α-Arylidene Diacylglycerol-Lactones (DAG-Lactones) as Selective Ras Guanine-Releasing Protein 3 (RasGRP3) Ligands

  摘要：

  Diacylglycerol-lactones have proven to be a powerful template for the design of potent ligands targeting CI domains, the recognition motif for the cellular second messenger diacylglycerol. A major objective has been to better understand the structure activity relations distinguishing the seven families of signaling proteins that contain such domains, of which the protein kinase C (PKC) and RasGRP families are of particular interest. Here, we synthesize a series of aryl- and alkyl-substituted diacylglycerol-lactones and probe their relative selectivities for RasGRP3 versus PKC. Compound 96 showed 73-fold selectivity relative to PKC alpha 45 and 45-fold selectivity relative to PKC epsilon for in vitro binding activity. Likewise, in intact cells, compound 96 induced Ras activation, a downstream response to RasGRP stimulation, with 8-29 fold selectivity relative to PKC delta S299 phosphorylation, a measure of PKC delta stimulation.

  DOI：

  10.1021/acs.jmedchem.8b00661

文献信息

• α-Arylidene Diacylglycerol-Lactones (DAG-Lactones) as Selective Ras Guanine-Releasing Protein 3 (RasGRP3) Ligands
  作者：Jihyae Ann、Agnes Czikora、Amandeep S. Saini、Xiaoling Zhou、Gary A. Mitchell、Nancy E. Lewin、Megan L. Peach、Peter M. Blumberg、Jeewoo Lee

  DOI：10.1021/acs.jmedchem.8b00661

  日期：2018.7.26

  Diacylglycerol-lactones have proven to be a powerful template for the design of potent ligands targeting CI domains, the recognition motif for the cellular second messenger diacylglycerol. A major objective has been to better understand the structure activity relations distinguishing the seven families of signaling proteins that contain such domains, of which the protein kinase C (PKC) and RasGRP families are of particular interest. Here, we synthesize a series of aryl- and alkyl-substituted diacylglycerol-lactones and probe their relative selectivities for RasGRP3 versus PKC. Compound 96 showed 73-fold selectivity relative to PKC alpha 45 and 45-fold selectivity relative to PKC epsilon for in vitro binding activity. Likewise, in intact cells, compound 96 induced Ras activation, a downstream response to RasGRP stimulation, with 8-29 fold selectivity relative to PKC delta S299 phosphorylation, a measure of PKC delta stimulation.