1-fluoro-3,6,9,12,15-pentaoxaoctadec-17-yne | 1378928-87-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-fluoro-3,6,9,12,15-pentaoxaoctadec-17-yne
• 英文别名: 3-[2-[2-[2-[2-(2-Fluoroethoxy)ethoxy]ethoxy]ethoxy]ethoxy]prop-1-yne
• CAS: 1378928-87-0
• 化学式: C₁₃H₂₃FO₅
• 分子量: 278.321
• InChiKey: OXAQEVMMYKMTFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  19
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-fluoro-3,6,9,12,15-pentaoxaoctadec-17-yne 、 (R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以6%的产率得到(R)-2-(N-(4-(2-(2-(2-(2-(4-(16-fluoro-2,5,8,11,14-pentaoxahexadecyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g
• 作为产物：
  描述：

  对甲苯磺酸氟乙酯 、 丙炔基-四聚乙二醇 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 16.17h， 以90%的产率得到1-fluoro-3,6,9,12,15-pentaoxaoctadec-17-yne
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g

文献信息

• Inverse 1,2,3-Triazole-1-yl-ethyl Substituted Hydroxamates as Highly Potent Matrix Metalloproteinase Inhibitors: (Radio)synthesis, in Vitro and First in Vivo Evaluation
  作者：Verena Hugenberg、Burkhard Riemann、Sven Hermann、Otmar Schober、Michael Schäfers、Katrin Szardenings、Artem Lebedev、Umesh Gangadharmath、Hartmuth Kolb、Joseph Walsh、Wei Zhang、Klaus Kopka、Stefan Wagner

  DOI：10.1021/jm4006753

  日期：2013.9.12

  Noninvasive imaging and quantification of matrix metalloproteinase (MMP) activity in vivo are of great (pre)clinical interest. This can potentially be realized by using radiolabeled MMP inhibitors (MMPIs) as positron emission tomography (PET) imaging agents. Triazole-substituted MMPIs, discovered by our group, are highly potent inhibitors of MMP-2, -8, -9, and -13. The triazole ring and its position contribute significantly to the potency of the MMP inhibitor. To evaluate structure activity relationships (SARs) of the initially discovered triazole-substituted MMPIs, an additional CH2-group between the backbone of the molecule and the triazole core was inserted, and the triazole ring was "inversed" by switching the alkyne and azide groups. Similar to the original triazole-substituted hydroxamates, the inverse triazole MMPIs are excellent inhibitors with promising in vivo properties. Pharmacokinetic properties and metabolic stability of an F-18-labeled candidate in mice were investigated.
• A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation
  作者：Verena Hugenberg、Hans-Jörg Breyholz、Burkhard Riemann、Sven Hermann、Otmar Schober、Michael Schäfers、Umesh Gangadharmath、Vani Mocharla、Hartmuth Kolb、Joseph Walsh、Wei Zhang、Klaus Kopka、Stefan Wagner

  DOI：10.1021/jm300199g

  日期：2012.5.24

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.