[2-(3,4-dimethoxyphenyl)ethyl](isobutylidene)amine | 459831-95-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [2-(3,4-dimethoxyphenyl)ethyl](isobutylidene)amine
• 英文别名: N-[2-(3,4-dimethoxyphenyl)ethyl]-2-methylpropan-1-imine
• CAS: 459831-95-9
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: KFDBLQVMVGRMJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [2-(3,4-dimethoxyphenyl)ethyl](isobutylidene)amine 在 三氟乙酸 作用下， 90.0 ℃ 、1.38 MPa 条件下， 反应 0.08h， 生成 1‐isopropyl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline
  参考文献：
  名称：

  Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies

  摘要：

  Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA. XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.

  DOI：

  10.1021/jm9014026
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 、 异丁醛 反应 1.5h， 以80%的产率得到[2-(3,4-dimethoxyphenyl)ethyl](isobutylidene)amine
  参考文献：
  名称：

  α-亚磺酰胺的串联Pummerer / Mannich环化级联反应是制备氮杂杂环的方法。

  摘要：

  通过伯胺与酮的缩合，然后使所得的亚胺与乙基亚磺酰基乙酰氯反应，然后用高碘酸钠氧化，可以方便地制备一系列α-亚磺酰胺基。当用p-TsOH处理时，通过涉及初始Pummerer反应，随后将所得N-酰基亚胺离子随后环化到束缚的芳族环上的机理发生环化以产生稠合的异喹啉内酰胺。根据Nazarov型4pi-电环反应，然后将pi环化到N-酰基亚胺离子受阻最小的一侧，合理化了单个非对映异构体的分离。用于产生α-酰基硫鎓离子中间体的另一种方法涉及双（乙基亚硫酰基乙酰基）乙酰胺与四氟硼酸二甲基（甲基）硫代on（DMTSF）的反应。用DMTSF处理数种双-乙基亚磺酰胺通过相关方法以高收率递送了新颖的螺-杂环作为单一非对映异构体。与该级联序列相关的收敛性和立体化学控制使其特别适合于天然产物支架的组装。一些初步的研究针对了甲基安息香和去甲异叶核苷。当将模型Z-en氨基亚砜33与对-TsOH一起加热时，作为单一非对映异

  DOI：

  10.1021/jo020083x

文献信息

• Rapid and diverse route to natural product-like biaryl ether containing macrocycles
  作者：Pierre Cristau、Jean-Pierre Vors、Jieping Zhu

  DOI：10.1016/j.tet.2003.08.031

  日期：2003.9

  four-component reaction and an intramolecular nucleophilic aromatic substitution (SNAr) has been developed for the rapid access to biaryl-ether containing macrocycles. In the course of this study, we documented that ammonium chloride can promote the Ugi-4CR in non-polar aprotic solvent (toluene) without the interference of an alternative Passerini reaction. Solid phase synthesis of macrocycles by this two-step

  涉及的Ugi四组分反应和分子内的亲核芳香取代（S两步序列Ñ AR）已被开发为快速访问包含大环化合物的二芳基-醚。在本研究过程中，我们记录了氯化铵可在非极性非质子传递溶剂（甲苯）中促进Ugi-4CR，而不会受到其他Passerini反应的干扰。还使用聚合物（Wang树脂）负载的α-（4'-氟-3'-硝基）苯乙基异氰基乙酸酯作为输入之一，开发了通过此两步序列的大环化合物的固相合成。
• Tandem Pummerer/Mannich Cyclization Cascade of α-Sulfinylamides as a Method To Prepare Aza-Heterocycles
  作者：Albert Padwa、Todd M. Heidelbaugh、Jeffrey T. Kuethe、Michael S. McClure、Qiu Wang

  DOI：10.1021/jo020083x

  日期：2002.8.1

  particularly suited for the assembly of natural product scaffolds. Some preliminary studies were directed toward both mesembrine and deethylibophyllidine. When the model Z-enamido sulfoxide 33 was heated with p-TsOH, a 80% yield of tosylate 34 was obtained as a single diastereomer. In this case, the carbocation intermediate derived from cyclization onto the terminal pi-bond was trapped with p-TsOH from the least

  通过伯胺与酮的缩合，然后使所得的亚胺与乙基亚磺酰基乙酰氯反应，然后用高碘酸钠氧化，可以方便地制备一系列α-亚磺酰胺基。当用p-TsOH处理时，通过涉及初始Pummerer反应，随后将所得N-酰基亚胺离子随后环化到束缚的芳族环上的机理发生环化以产生稠合的异喹啉内酰胺。根据Nazarov型4pi-电环反应，然后将pi环化到N-酰基亚胺离子受阻最小的一侧，合理化了单个非对映异构体的分离。用于产生α-酰基硫鎓离子中间体的另一种方法涉及双（乙基亚硫酰基乙酰基）乙酰胺与四氟硼酸二甲基（甲基）硫代on（DMTSF）的反应。用DMTSF处理数种双-乙基亚磺酰胺通过相关方法以高收率递送了新颖的螺-杂环作为单一非对映异构体。与该级联序列相关的收敛性和立体化学控制使其特别适合于天然产物支架的组装。一些初步的研究针对了甲基安息香和去甲异叶核苷。当将模型Z-en氨基亚砜33与对-TsOH一起加热时，作为单一非对映异
• Identification of 3,4-Dihydroisoquinoline-2(1<i>H</i>)-sulfonamides as Potent Carbonic Anhydrase Inhibitors: Synthesis, Biological Evaluation, and Enzyme−Ligand X-ray Studies
  作者：Rosaria Gitto、Stefano Agnello、Stefania Ferro、Laura De Luca、Daniela Vullo、Jiri Brynda、Pavel Mader、Claudiu T. Supuran、Alba Chimirri

  DOI：10.1021/jm9014026

  日期：2010.3.25

  Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA. XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.