2-[(2-丁基咪唑-1-基)甲氧基]乙基-三甲基硅烷 | 134405-73-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-[(2-丁基咪唑-1-基)甲氧基]乙基-三甲基硅烷
• 英文名称: 2-Butyl-1-[[2-(trimethylsilyl)ethoxy]-methyl]-1H-imidazole
• 英文别名: 2-butyl-1-<<2-(trimethylsilyl)ethoxy>methyl>-1H-imidazole；2-butyl-1-<<2-(trimethylsilyl)ethoxy>methyl>imidazole；1-SEM-2-butylimidazole；2-Butyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-imidazole；2-butyl-1-[2-(trimethylsilyl)ethoxymethyl]-1H-imidazole；1H-Imidazole, 2-butyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-；2-[(2-butylimidazol-1-yl)methoxy]ethyl-trimethylsilane
• CAS: 134405-73-5
• 化学式: C₁₃H₂₆N₂OSi
• 分子量: 254.448
• InChiKey: ATLIAVRQKDQLGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(2-丁基咪唑-1-基)甲氧基]乙基-三甲基硅烷 在 盐酸 、 sodium hydroxide 、 四(三苯基膦)钯 、 正丁基锂 、 三丁基氯化锡 、 三乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 45.5h， 生成 (E)-3-<2-butyl-1-<(2-chlorophenyl)methyl>imidazol-5-yl>-2-heptenoic acid
  参考文献：
  名称：

  咪唑-5-丙烯酸：使用新型肽药效团模型设计的有效非肽血管紧张素II受体拮抗剂。

  摘要：

  已经开发了一系列含有取代的（E）-丙烯酸的新型非肽血管紧张素II受体拮抗剂。专利文献中发现的1（一种咪唑5-乙酸）在AII的新型药效团模型上的覆盖物表明，酸侧链的延伸和第二个芳基残基的附着可模拟AII的C端苯丙氨酸区域会导致活动增加。对咪唑核C-5上延伸的酸侧链的研究导致发现（E）-丙烯酸5作为进一步探索的有希望的起点。如建模所预测的，在丙烯酸侧链上的苄基取代以模拟苯丙氨酸产生的效价增加。对新引入的芳环的SAR进行的广泛研究表明，富电子的杂芳基环具有更高的活性，尤其是在体内大鼠模型中。已经显示出化合物40，（E）-3- [2-丁基-1-[[（2-氯苯基）甲基]咪唑-5-基] -2-[（（2-噻吩基）甲基] -2-丙酸。成为有效，具有竞争性和口服活性的小分子AT-1受体拮抗剂。与化合物1相比，它的结合亲和力提高了2个数量级，体内效价提高了10倍，在开发更有效的非肽类血管紧张素II受体拮抗剂中

  DOI：

  10.1021/jm00099a013
• 作为产物：
  描述：

  2-(三甲基硅烷基)乙氧甲基氯 在 正丁基锂 、 sodium hydride 作用下， 反应 5.75h， 生成 2-[(2-丁基咪唑-1-基)甲氧基]乙基-三甲基硅烷
  参考文献：
  名称：

  Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase pK_a Values by NMR

  摘要：

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.

  DOI：

  10.1021/jo960367f

文献信息

• 4-Diazinyl- and 4-Pyridinylimidazoles: Potent Angiotensin II Antagonists. A Study of Their Activity and Computational Characterization
  作者：J. S. Harmat Nicholas、Raffaello Giorgi、Fabrizio Bonaccorsi、Guido Cerbai、Spartaco M. Colombani、Anna R. Renzetti、Rocco Cirillo、Alessandro Subissi、Giuliano Alagona

  DOI：10.1021/jm00015a015

  日期：1995.7

  A series of N-[biphenylyl(tetrazolyl)methyl]-2-butylimidazoles containing variously substituted diazine or pyridine moieties either as their free bases or N-oxide derivatives attached to the 4-position of the imidazole ring was synthesized and tested for interaction with the AT1 receptors of rat adrenal cortex membranes (receptor binding assay). Some compounds were then chosen for further evaluation

  合成了一系列N- [联苯基（四唑基甲基）甲基] -2-丁基咪唑，它们含有不同取代的二嗪或吡啶部分作为游离碱或连接到咪唑环4位的N-氧化物衍生物，并测试了与大鼠肾上腺皮质膜的AT1受体（受体结合测定）。然后选择一些化合物以在体内进行进一步评估，以在有意识的血压正常的大鼠中由A II诱导的升压反应。发现在AT1结合测定中最有效的是其中二嗪或吡啶环氮与两个杂芳族环之间的连接点相邻的化合物，例如2-丁基-4-（3,6-二甲基吡嗪-2- yl）-1-[[[2'-（1H-四唑-5-基）-联苯-4-基]甲基] -1H-咪唑（3b）或2-丁基-4- [5-（甲氧羰基）吡啶- 2-基] -1-[[2' -（1H-四唑+++-5-基）联苯-4-基]甲基] -1H-咪唑（6c）。与2-丁基-4-[（3-甲氧基羰基）-6-甲基-N-一样，在吡啶环氮上邻有一个稳定基团的吡啶N-氧化物咪唑的结合亲和力和口服活性得到显着改善。氧吡啶吡啶-2-基]
• C−H Bonds as Ubiquitous Functionality: A General Approach to Complex Arylated Imidazoles via Regioselective Sequential Arylation of All Three C−H Bonds and Regioselective <i>N</i>-Alkylation Enabled by SEM-Group Transposition
  作者：Jung Min Joo、B. Barry Touré、Dalibor Sames

  DOI：10.1021/jo100727j

  日期：2010.8.6

  SEM-group deprotection (trans-N-alkylation) allows for regioselective N-alkylation of complex imidazoles. The sequential C-arylation enabled by the SEM-switch allowed us to produce a variety of mono-, di-, and triarylimidazoles using diverse bromo- and chloroarenes. Using our approach, the synthesis of individual compounds or libraries of analogues can begin from either the parent imidazole or a substituted

  咪唑是杂环杂环唑族的一个重要基团，常见于药物、候选药物、过渡金属催化剂的配体和其他分子功能材料中。由于它们在学术界和工业界的广泛应用，需要用于生成功能化咪唑衍生物的新方法和策略。我们在这里描述了一种合成复杂芳基咪唑的通用和综合方法，其中咪唑核心的所有三个 C-H 键都可以以区域选择性和顺序方式进行芳基化。我们报告了用于 SEM-咪唑选择性 C5-和 C2-芳基化的新催化方法，并基于 C-H 键和杂环的电子特性为观察到的位置选择性提供了机械假设。重要的，在实际实验室条件下，芳基溴化物和低成本芳基氯化物可用作芳烃供体。为了避免 C-4 位置的低反应性，我们开发了 SEM 开关，将 SEM 基团从 N-1 转移到 N-3 氮，从而能够制备 4-芳基咪唑和连续的 C4-C5-芳基化咪唑核。此外，选择性 N3-烷基化，然后是 SEM-基团脱保护（反式-N-烷基化）允许复合咪唑的区域选择性N-烷基化。由
• Amines That Transport Protons across Bilayer Membranes:  Synthesis, Lysosomal Neutralization, and Two-Phase p<i>K</i>_a Values by NMR
  作者：Gene M. Dubowchik、Linda Padilla、Kurt Edinger、Raymond A. Firestone

  DOI：10.1021/jo960367f

  日期：1996.1.1

  It is desirable to be able to control the pH of lysosomes. A collection of lipophilic, nitrogenous bases, designed to act as membrane-active, catalytic proton transfer agents, were prepared and their effective pK(a)s measured in a vigorously stirred, two-phase system. One phase was a phosphate buffer whose pH was varied over the range ca, 1-11. The other was an immiscible, deuterated organic solvent in which the compounds preferentially resided even when protonated. When chemical shift changes versus the pH of the buffer were plotted, clear pK(a) curves were generated that are relevant to transmembrane proton transfer behavior. The two-phase pK(a)s increased with increasing counterion lipophilicity and with increasing organic solvent polarity, The compounds were also tested for their ability to neutralize the acidity of lysosomes, a model for other acidic vesicles involved in drug sorting. The most successful of these, imidazole 6a, has > 100 times the neutralizing power of ammonia, a standard lysosomotropic amine, causing a 1.7 unit rise in lysosomal pH of RAW cells at 0.1 mM, compared to a 0.2 and 1.4 unit rise for ammonium chloride at 0.1 and 10 mM, respectively.
• Imidazole-5-acrylic acids: potent nonpeptide angiotensin II receptor antagonists designed using a novel peptide pharmacophore model
  作者：R. M. Keenan、J. Weinstock、J. A. Finkelstein、R. G. Franz、D. E. Gaitanopoulos、G. R. Girard、D. T. Hill、T. M. Morgan、J. M. Samanen

  DOI：10.1021/jm00099a013

  日期：1992.10

  l]-2- propenoic acid, has been shown to be a potent, competitive, and orally active small molecule AT-1 receptor antagonist. It exhibits a 2 orders of magnitude increase in binding affinity and a 10-fold improvement in in vivo potency as compared to compound 1 and represents an important milestone in the development of even more potent nonpeptide angiotensin II receptor antagonists.

  已经开发了一系列含有取代的（E）-丙烯酸的新型非肽血管紧张素II受体拮抗剂。专利文献中发现的1（一种咪唑5-乙酸）在AII的新型药效团模型上的覆盖物表明，酸侧链的延伸和第二个芳基残基的附着可模拟AII的C端苯丙氨酸区域会导致活动增加。对咪唑核C-5上延伸的酸侧链的研究导致发现（E）-丙烯酸5作为进一步探索的有希望的起点。如建模所预测的，在丙烯酸侧链上的苄基取代以模拟苯丙氨酸产生的效价增加。对新引入的芳环的SAR进行的广泛研究表明，富电子的杂芳基环具有更高的活性，尤其是在体内大鼠模型中。已经显示出化合物40，（E）-3- [2-丁基-1-[[（2-氯苯基）甲基]咪唑-5-基] -2-[（（2-噻吩基）甲基] -2-丙酸。成为有效，具有竞争性和口服活性的小分子AT-1受体拮抗剂。与化合物1相比，它的结合亲和力提高了2个数量级，体内效价提高了10倍，在开发更有效的非肽类血管紧张素II受体拮抗剂中