2-((1-((triethylsilyl)oxy)oct-1-en-1-yl)thio)pyridine | 863783-28-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-((1-((triethylsilyl)oxy)oct-1-en-1-yl)thio)pyridine
• 英文别名: 2-({(1E)-1-[(triethylsilyl)oxy]oct-1-en-1-yl}thio)pyridine；triethyl-[(E)-1-pyridin-2-ylsulfanyloct-1-enoxy]silane
• CAS: 863783-28-2
• 化学式: C₁₉H₃₃NOSSi
• 分子量: 351.629
• InChiKey: VTTMCOCECFYIRC-KNTRCKAVSA-N

物化性质

• 沸点：
  418.5±41.0 °C(Predicted)
• 密度：
  0.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.01
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  47.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-((1-((triethylsilyl)oxy)oct-1-en-1-yl)thio)pyridine 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二甲基甲酰胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 19.67h， 生成
  参考文献：
  名称：

  A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids

  摘要：

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.020
• 作为产物：
  描述：

  三乙基氯硅烷 、 S-(pyridin-2-yl)octanethioate 在 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.17h， 生成 2-((1-((triethylsilyl)oxy)oct-1-en-1-yl)thio)pyridine
  参考文献：
  名称：

  Alkyl carbamate-substituted beta-lactones, process and intermediate products for their preparation, and pharmaceutical compositions containing them

  摘要：

  取代的β-内酰胺（氧杂环丙烷酮）对应于公式I， 其中R1，R2和n具有说明书中给出的含义，以及包含这些化合物的药物组合物，并具有胰腺脂肪酶抑制作用，以及用于制备公式I化合物和此过程中间体的方法。

  公开号：

  US20050197386A1

文献信息

• Alkyl carbamate-substituted beta-lactones, process and intermediate products for their preparation, and pharmaceutical compositions containing them
  申请人：Antel Jochen

  公开号：US20050197386A1

  公开（公告）日：2005-09-08

  Substituted β-lactones (oxetanones) corresponding to the formula I, wherein R 1 , R 2 and n have the meanings given in the specification, and pharmaceutical compositions which contain these compounds and have a pancreatic lipase-inhibiting action, as well as a process for the preparation of the compounds of Formula I and intermediate products of this process.

  取代的β-内酰胺（氧杂环丙烷酮）对应于公式I， 其中R1，R2和n具有说明书中给出的含义，以及包含这些化合物的药物组合物，并具有胰腺脂肪酶抑制作用，以及用于制备公式I化合物和此过程中间体的方法。
• A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids
  作者：Mingzhao Zhu、Wayne D. Harshbarger、Omar Robles、Joanna Krysiak、Kenneth G. Hull、Sung Wook Cho、Robyn D. Richardson、Yanyan Yang、Andres Garcia、Lindsey Spiegelman、Bianca Ramirez、Christopher T. Wilson、Ju Anne Yau、James T. Moore、Caitlen B. Walker、James C. Sacchettini、Wenshe R. Liu、Stephan A. Sieber、Jeffrey W. Smith、Daniel Romo

  DOI：10.1016/j.bmc.2017.01.020

  日期：2017.6

  The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, B-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance. (C) 2017 Elsevier Ltd. All rights reserved.