m-Methoxy-N-benzyliden-2-amino-propan | 13033-51-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: m-Methoxy-N-benzyliden-2-amino-propan
• 英文别名: N-[(E)-(3-Methoxyphenyl)methylidene]-2-propanamine；1-(3-methoxyphenyl)-N-propan-2-ylmethanimine
• CAS: 13033-51-7
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: HKMBOQDDARZGHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  m-Methoxy-N-benzyliden-2-amino-propan 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 3-(4-(1H-pyrazol-4-yl)phenyl)-1-isopropyl-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：

  异丙胺 、 3-甲氧基苯甲醛 以 甲醇 为溶剂， 反应 0.25h， 生成 m-Methoxy-N-benzyliden-2-amino-propan
  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

文献信息

• Introducing a sulfone-embedded anhydride to the anhydride-imine reaction for the modular synthesis of N-heterocyclic sulfones bearing vicinal stereocenters
  作者：Timothy K. Beng、Jorge Garcia、Jane Eichwald、Claire Borg

  DOI：10.1039/d3ra01812a

  日期：——

  A flexible approach to sp³-rich N-heterocyclic sulfones, which hinges on the efficient annulation of an easy-to-prepare sulfone-embedded anhydride with 1,3-azadienes and aryl aldimines, is described.

  本文介绍了一种灵活的富含 sp3 的 N-杂环砜的制备方法，该方法的关键在于将一种易于制备的砜嵌入酸酐与 1,3-氮杂二烯和芳基醛亚胺进行高效环化反应。
• 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.
• Cobalt-Catalyzed α-Arylation of Substituted α-Halogeno β-Lactams
  作者：Vanessa Koch、Mélanie M. Lorion、Etienne Barde、Stefan Bräse、Janine Cossy

  DOI：10.1021/acs.orglett.9b02122

  日期：2019.8.16

  The treatment of 3-bromo beta-lactams by an aryl Grignard, in the presence of CoCl2 (2 mol %) and TMEDA (2 mol %) in THF, produces 3-aryl beta-lactams in good yields and excellent diastereoselectivity.