N-[(1E/Z)-[2-(benzyloxy)phenyl]methylene]-4-methoxyaniline | 304454-49-7

• 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: N-[(1E/Z)-[2-(benzyloxy)phenyl]methylene]-4-methoxyaniline
• 英文别名: (2-benzyloxybenzylidene)-(4-methoxyphenyl)-imine；N-[2-(benzyloxy)benzylidene]-4-methoxyaniline；N-(4-methoxyphenyl)-1-(2-phenylmethoxyphenyl)methanimine
• CAS: 304454-49-7
• 化学式: C₂₁H₁₉NO₂
• 分子量: 317.387
• InChiKey: OIBCEGGBDUQASW-UHFFFAOYSA-N

物化性质

• 沸点：
  496.6±35.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 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：

  N-[(1E/Z)-[2-(benzyloxy)phenyl]methylene]-4-methoxyaniline 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 乙醇 、 甲苯 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 反应 4.25h， 生成 4-(2-hydroxyphenyl)-1-(4-methoxyphenyl)-3,3-dimethylazetidin-2-one
  参考文献：
  名称：

  鉴定和优化3,3-二甲基-氮杂环丁烷-2-酮类化合物作为11β-羟类固醇脱氢酶1型的有效和选择性抑制剂（11β-HSD1）†

  摘要：

  3,3-二甲基-氮杂环丁烷-2-酮被鉴定为针对人和小鼠形式酶的有效和选择性11β-HSD1抑制剂。利用关键的极性相互作用并确定4S异构体的立体化学偏好性，对LLE进行结构指导的优化。代谢稳定性得到改善，可以口服，提供了适合临床前评估的工具化合物。

  DOI：

  10.1039/c3md00234a
• 作为产物：
  描述：

  甲氧苯胺 、 2-苄氧基苯甲醛 以 乙腈 为溶剂， 反应 0.5h， 生成 N-[(1E/Z)-[2-(benzyloxy)phenyl]methylene]-4-methoxyaniline
  参考文献：
  名称：

  Identification of small molecule sphingomyelin synthase inhibitors

  摘要：

  Sphingomyelin synthase (SMS), which catalyzes ceramide as one of the substrates to produce sphingomyelin, is a critical factor in the sphingolipid biosynthesis pathway. Recent studies indicated that SMS could serve as a novel potential drug target for the treatment of various metabolic diseases such as insulin resistance and atherosclerosis. However, very few small-molecule inhibitors of SMS are known. In this study, we performed structure-based virtual screening in combination with chemical synthesis and bioassay and discovered a class of small-molecule SMS inhibitors. The most potent compound exhibited an IC50 value lower than 20 mu M in an in vitro enzymatic assay. To the best of our knowledge, this is the first time that small-molecule SMS inhibitors with potency close to the micromolar range are publicly revealed. The structure-activity relationship demonstrated by this class of compounds provides insights into the structural features that are essential for effective SMS inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.002

文献信息

• Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation
  作者：Mathis Hodge、Qiao-Hong Chen、Susan Bane、Shubhada Sharma、Maura Loew、Abhijit Banerjee、Ana A. Alcaraz、James P. Snyder、David G.I. Kingston

  DOI：10.1016/j.bmcl.2009.03.063

  日期：2009.5

  bioactive tubulin-binding conformation of paclitaxel (Taxol™) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the

  了解紫杉醇 (Taxol ™ )的生物活性微管蛋白结合构象对于全面了解这种重要抗癌药物的生物活性至关重要，并且可能对简化类似物的设计也很重要。生物活性构象已被证明最接近于 T-紫杉醇构象。作为对这一结论的进一步检验，紫杉醇类似物4被设计为具有活性所需的所有化学功能但不能采用 T-紫杉醇构象的化合物。的合成和生物测定4证实了它的缺乏活动，并因此提供了用于在T-紫杉醇构象生物活性微管蛋白结合的构象的进一步支持。
• Identification of small molecule sphingomyelin synthase inhibitors
  作者：Xiaodong Deng、Fu Lin、Ya Zhang、Yan Li、Lu Zhou、Bin Lou、Yue Li、Jibin Dong、Tingbo Ding、Xiancheng Jiang、Renxiao Wang、Deyong Ye

  DOI：10.1016/j.ejmech.2013.12.002

  日期：2014.2

  Sphingomyelin synthase (SMS), which catalyzes ceramide as one of the substrates to produce sphingomyelin, is a critical factor in the sphingolipid biosynthesis pathway. Recent studies indicated that SMS could serve as a novel potential drug target for the treatment of various metabolic diseases such as insulin resistance and atherosclerosis. However, very few small-molecule inhibitors of SMS are known. In this study, we performed structure-based virtual screening in combination with chemical synthesis and bioassay and discovered a class of small-molecule SMS inhibitors. The most potent compound exhibited an IC50 value lower than 20 mu M in an in vitro enzymatic assay. To the best of our knowledge, this is the first time that small-molecule SMS inhibitors with potency close to the micromolar range are publicly revealed. The structure-activity relationship demonstrated by this class of compounds provides insights into the structural features that are essential for effective SMS inhibition. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Identification and optimisation of 3,3-dimethyl-azetidin-2-ones as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
  作者：William McCoull、Martin Augustin、Caroline Blake、Anne Ertan、Elaine Kilgour、Stephan Krapp、Jane E. Moore、Nicholas J. Newcombe、Martin J. Packer、Amanda Rees、John Revill、James S. Scott、Nidhal Selmi、Stefan Gerhardt、Derek J. Ogg、Stefan Steinbacher、Paul R. O. Whittamore

  DOI：10.1039/c3md00234a

  日期：——

  3,3-Di-methyl-azetidin-2-ones were identified as potent and selective 11β-HSD1 inhibitors against the human and mouse forms of the enzyme. Structure guided optimisation of LLE was conducted, utilising a key polar interaction and identifying stereochemical preference for the 4S isomer. Metabolic stability was improved to afford oral exposure, providing tool compounds suitable for pre-clinical evaluation

  3,3-二甲基-氮杂环丁烷-2-酮被鉴定为针对人和小鼠形式酶的有效和选择性11β-HSD1抑制剂。利用关键的极性相互作用并确定4S异构体的立体化学偏好性，对LLE进行结构指导的优化。代谢稳定性得到改善，可以口服，提供了适合临床前评估的工具化合物。