1-((hept-6-en-1-yloxy)methyl)adamantane | 1307309-76-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-((hept-6-en-1-yloxy)methyl)adamantane
• 英文别名: 1-(Hept-6-enoxymethyl)adamantane
• CAS: 1307309-76-7
• 化学式: C₁₈H₃₀O
• 分子量: 262.436
• InChiKey: WVKWVQQJGWAEQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-((hept-6-en-1-yloxy)methyl)adamantane 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 9-硼双环[3.3.1]壬烷 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 N-(4-(7-(adamantan-1-ylmethoxy)heptyl)phenyl)-1-cyanocyclopropanecarboxamide
  参考文献：
  名称：

  Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells

  摘要：

  Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.

  DOI：

  10.1021/jm2001053
• 作为产物：
  描述：

  7-溴-1-庚烯 、 1-金刚烷甲醇 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.75h， 以85%的产率得到1-((hept-6-en-1-yloxy)methyl)adamantane
  参考文献：
  名称：

  Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells

  摘要：

  Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.

  DOI：

  10.1021/jm2001053

文献信息

• Three-component aminofluorination of alkenes with electronically rich amino sources
  作者：Yang Li、Jiamin Bao、Yu Zhang、Xue Peng、Weijie Yu、Tao Wang、Dengtao Yang、Qun Liu、Qian Zhang、Junkai Fu

  DOI：10.1016/j.chempr.2022.02.014

  日期：2022.4

  alkylaminyl radical formation and maintain the nucleophilicity of fluoride ion. This protocol exhibits excellent functional-group tolerance toward various aryl and unactivated alkenes, furnishing the corresponding β-fluoroamines with high regioselectivity. Mechanistic investigation reveals an aziridinium intermediate via a radical pathway. The synthetic utility of this transformation was demonstrated by

  通过 umpolung 策略开发了具有丰富电子氨基源的烯烃的第一个分子间三组分氨基氟化。在该反应中，亲电的N-溴二烷基胺被用作胺亲电子试剂，而多功能 AgF 同时作为亲核氟化物源和还原催化剂，首次与N引发单电子转移-溴二烷基胺。添加六氟异丙醇作为助溶剂对于促进质子化烷基胺自由基的形成和保持氟离子的亲核性至关重要。该协议对各种芳基和未活化烯烃表现出优异的官能团耐受性，为相应的 β-氟胺提供了高区域选择性。机理研究揭示了一种通过自由基途径产生的氮丙啶中间体。这种转化的合成效用通过几种生物活性分子的氨基氟化来证明，包括通往利扎曲坦类似物的有效途径。我们预计我们的发现有望为药物化学和胺化反应的新发现带来希望。
• Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells
  作者：Andrew J. Kennedy、Thomas P. Mathews、Yugesh Kharel、Saundra D. Field、Morgan L. Moyer、James E. East、Joseph D. Houck、Kevin R. Lynch、Timothy L. Macdonald

  DOI：10.1021/jm2001053

  日期：2011.5.26

  Sphingosine 1-phosphate (S1P) is a bioactive lipid that has been identified as an accelerant of cancer progression. The sphingosine kinases (SphKs) are the sole producers of S1P, and thus, SphK inhibitors may prove effective in cancer mitigation and chemosensitization. Of the two SphKs, SphK1 overexpression has been observed in a myriad of cancer cell lines and tissues and has been recognized as the presumptive target over that of the poorly characterized SphK2. Herein, we present the design and synthesis of amidine-based nanomolar SphK1 subtype-selective inhibitors. A homology model of SphK1, trained with this library of amidine inhibitors, was then used to predict the activity of additional, more potent, inhibitors. Lastly, select amidine inhibitors were validated in human leukemia U937 cells, where they significantly reduced endogenous S1P levels at nanomolar concentrations.