2-{[(3-methoxyphenyl)methylene]amino}ethanol | 70365-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-{[(3-methoxyphenyl)methylene]amino}ethanol
• 英文别名: 2-{(E)-[(3-Methoxyphenyl)methylidene]amino}ethan-1-ol；2-[(3-methoxyphenyl)methylideneamino]ethanol
• CAS: 70365-15-0
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: APUUGQJAJYCTHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-{[(3-methoxyphenyl)methylene]amino}ethanol 在 sodium tetrahydroborate 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 3-(4-bromo-2-(2-hydroxyethoxy)phenyl)-1-(2-hydroxyethyl)-1-(3-methoxybenzyl)urea
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r
• 作为产物：
  描述：

  C.I.酸性橙108 、 3-甲氧基苯甲醛 以 苯 为溶剂， 反应 0.25h， 生成 2-{[(3-methoxyphenyl)methylene]amino}ethanol
  参考文献：
  名称：

  通过一锅（Ugi-3CR / Aza Diels-Alder / N-酰化/芳构化/ SN2）法合成多杂环吡咯并[3,4-b]吡啶-5-酮。法利帕米尔新型氮杂类似物的合适替代物。

  摘要：

  我们描述了通过级联过程（Ugi-3CR / Aza Diels-Alder / N-酰化/芳构化）以20％至95％的总产率一锅合成二十个多杂环吡咯并[3,4-b]吡啶基-5-酮，以及通过改进的级联过程（Ugi-3CR / Aza Diels-Alder / N-酰化/芳香化/ SN2）得到的四个在药理上有希望的类似物：两个哌嗪连接的吡咯并[3,4-b]吡啶-5-酮33％和34％，以及几个Falipamil氮杂类似物，总产率为30％和35％。值得一提的是，发现了良好的底物范围，因为最终产品配有烷基，芳基和杂环取代基。使用链环可互变异构异氰酸酯（作为Ugi型三组分反应的关键试剂）可以快速有效地组装多取代的羟吲哚，这些化合物原位用于复杂的产品，

  DOI：

  10.3390/molecules23040763

文献信息

• Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors
  作者：Yan Yin、Li Lin、Claudia Ruiz、Susan Khan、Michael D. Cameron、Wayne Grant、Jennifer Pocas、Nibal Eid、HaJeung Park、Thomas Schröter、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm400062r

  日期：2013.5.9

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.
• Synthesis of Polyheterocyclic Pyrrolo[3,4-b]pyridin-5-ones via a One-Pot (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2) Process. A Suitable Alternative towards Novel Aza-Analogues of Falipamil
  作者：Angel Zamudio-Medina、Ailyn García-González、Genesis Herrera-Carrillo、Daniel Zárate-Zárate、Adriana Benavides-Macías、Joaquín Tamariz、Ilich Ibarra、Alejandro Islas-Jácome、Eduardo González-Zamora

  DOI：10.3390/molecules23040763

  日期：——

  We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked pyrrolo[3,4-b]pyridin-5-ones in 33 and 34%

  我们描述了通过级联过程（Ugi-3CR / Aza Diels-Alder / N-酰化/芳构化）以20％至95％的总产率一锅合成二十个多杂环吡咯并[3,4-b]吡啶基-5-酮，以及通过改进的级联过程（Ugi-3CR / Aza Diels-Alder / N-酰化/芳香化/ SN2）得到的四个在药理上有希望的类似物：两个哌嗪连接的吡咯并[3,4-b]吡啶-5-酮33％和34％，以及几个Falipamil氮杂类似物，总产率为30％和35％。值得一提的是，发现了良好的底物范围，因为最终产品配有烷基，芳基和杂环取代基。使用链环可互变异构异氰酸酯（作为Ugi型三组分反应的关键试剂）可以快速有效地组装多取代的羟吲哚，这些化合物原位用于复杂的产品，