(2-methoxyethoxy)methyl (2E)-5-(trimethylsilyl)pent-2-en-4-ynoate | 1092115-41-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2-methoxyethoxy)methyl (2E)-5-(trimethylsilyl)pent-2-en-4-ynoate
• CAS: 1092115-41-7
• 化学式: C₁₂H₂₀O₄Si
• 分子量: 256.374
• InChiKey: GOEVMYCVBMGGFG-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.59
• 重原子数：
  17.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2-methoxyethoxy)methyl (2E)-5-(trimethylsilyl)pent-2-en-4-ynoate 在 盐酸 、 草酰氯 、 triethylphosphite copper(I) iodide complex 、 三异丙基硅烷 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 cesium fluoride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 (2E)-N-hydroxy-3-(1-((E)-4,4-dimethyl-1-phenylpent-1-en-3-yl)-1H-1,2,3-triazol-4-yl)acrylamide
  参考文献：
  名称：

  基于点击的组蛋白脱乙酰基酶抑制剂的基于结构的优化

  摘要：

  以前，我们报道了一种基于点击化学的方法来合成一类新型的组蛋白脱乙酰基酶（HDAC）抑制剂[1]。发现前导化合物NSC746457与SAHA（伏立诺他州）一样有效。本文描述了通过使用HDAC2-TSA晶体结构对NSC746457进行的进一步优化。将NSC746457对接至HDAC2结合域表明，可以利用帽基结合基序侧翼的疏水残基Phe210进行结构优化。肉桂酸帽区​​域的亚甲基取代导致鉴定出更有效的HDAC抑制剂：异丙基衍生物5和叔丁基衍生物6，其IC 50值分别为22 nM和18 nM。

  DOI：

  10.1016/j.ejmech.2011.04.027
• 作为产物：
  描述：

  2-methoxyethoxymethyl 3-iodoprop-2-enoate 、 三甲基乙炔基硅 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以82%的产率得到(2-methoxyethoxy)methyl (2E)-5-(trimethylsilyl)pent-2-en-4-ynoate
  参考文献：
  名称：

  A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors

  摘要：

  This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 mu M in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works. (C) 2016 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2016.03.116

文献信息

• Histone Deacetylase Inhibitors through Click Chemistry
  作者：Jie Shen、Robert Woodward、James Patrick Kedenburg、Xianwei Liu、Min Chen、Lanyan Fang、Duxin Sun、Peng George Wang

  DOI：10.1021/jm8005355

  日期：2008.12.11

  Histone deacetylase inhibitors (HDACi) are a relatively new class of chemotherapy agents. Herein, we report a click-chemistry based approach to the synthesis of HDACi. Fourteen agents were synthesized from the combination of two alkyne and seven azido precursors. The inhibition of HDAC1 and HDAC8 was then determined by in vitro enzymatic assays, after which the cytotoxicity was evaluated in the NCI human cancer cell line screen. A lead compound 5g (NSC746457) was discovered that inhibited HDAC1 at an IC50 value of 104 +/- 30 nM and proved quite potent in the cancer cell line screen with GI(50) values ranging from 3.92 mu M to 10 nM. Thus, this click HDACi design has provided a new chemical scaffold that has not only revealed a lead compound, but one which is easily amendable to further structural modifications given the modular nature of this approach.