2-(2-(benzyloxy)phenyl)-2-(p-tolylamino)acetonitrile | 723248-54-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(2-(benzyloxy)phenyl)-2-(p-tolylamino)acetonitrile
• 英文别名: [2-(Benzyloxy)phenyl](4-toluidino)acetonitrile；2-(4-methylanilino)-2-(2-phenylmethoxyphenyl)acetonitrile
• CAS: 723248-54-2
• 化学式: C₂₂H₂₀N₂O
• 分子量: 328.414
• InChiKey: NXJCNRBMBWLIRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  45.05
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-(2-(benzyloxy)phenyl)-2-(p-tolylamino)acetonitrile 在 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 、 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 4.0h， 生成 5-(Aminomethyl)-5-(2-benzyloxyphenyl)-1-(p-tolyl)pyrrolidin-2-one
  参考文献：
  名称：

  Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs

  摘要：

  A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values < 20 A mu M. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g-j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.

  DOI：

  10.1007/s00044-016-1731-7
• 作为产物：
  描述：

  乙烷,三氯氟- 、 2-苄氧基苯甲醛 在 碘 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 2-(2-(benzyloxy)phenyl)-2-(p-tolylamino)acetonitrile
  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

• Anti-human immunodeficiency activity of novel 2-arylpyrrolidine analogs
  作者：Ashot H. Martirosyan、Sahak P. Gasparyan、Marina V. Alexanyan、Gohar K. Harutyunyan、Henry A. Panosyan、Raymond F. Schinazi

  DOI：10.1007/s00044-016-1731-7

  日期：2017.1

  A series of 26 new compounds were synthesized and screened for their anti-human immunodeficiency virus-1 and cytotoxicity activity. Of these, 14 were found to be inhibitors of human immunodeficiency virus replications in primary human lymphocytes with 50 % effective concentration values < 20 A mu M. Moreover, most of the compounds were cytotoxic to human lymphocytes, CEM, and Vero cells. Our structure activity relationship study identified different patterns. Compounds 2g-j and 4 (whose structure is closer to the loviride structure) were very potent. Comparing the activity of the compounds containing the 2-aryl substituents, we observed that compounds with benzyloxyphenyl groups were more potent. Compounds in which the 1-aryl moiety contained methyl group in 4- or 3,5-positions also showed high activity. In the series of compounds containing the nitrile, amine, and amide groups, we observed a decrease in activity with CN > NH2 > C(O)NH2. The difference of activity between the 5-membered and 4-membered rings compounds was not significant. This initial information could be used to design improved anti-human immunodeficiency virus compounds in this class.
• 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.