N,N-二乙基-2-异吲哚啉乙胺 | 73816-63-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: N,N-二乙基-2-异吲哚啉乙胺
• 英文名称: N,N-diethyl-2-(isoindolin-2-yl)ethan-1-amine
• 英文别名: N-<2-(N,N-Diethylamino)-ethyl>-isoindolin；2-(2-diethylamino-ethyl)-isoindoline；2-(2-Diaethylamino-aethyl)-isoindolin；Isoindoline, 2-(diethylaminoethyl)-；2-(1,3-dihydroisoindol-2-yl)-N,N-diethylethanamine
• CAS: 73816-63-4
• 化学式: C₁₄H₂₂N₂
• 分子量: 218.342
• InChiKey: ZLAHMPYKIVXKFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N-二乙基-2-异吲哚啉乙胺 、 碘甲烷 在 乙醇 作用下， 生成 2-[2-(diethyl-methyl-ammonio)-ethyl]-2-methyl-isoindolinium; diiodide
  参考文献：
  名称：

  Hypotensive Agents. IV.¹ Hydrogenated Dialkylaminoalkyl Isoindole Derivatives²

  摘要：

  DOI：

  10.1021/ja01116a010
• 作为产物：
  描述：

  2-(2-(二乙胺基)乙基)异二氢吲哚-1,3-二酮 在 lithium aluminium tetrahydride 、 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 N,N-二乙基-2-异吲哚啉乙胺
  参考文献：
  名称：

  Synthesis and phospholipidosis effect of a series of cationic amphiphilic compounds: a case study to evaluate in silico and in vitro assays

  摘要：

  In recent years, a large number of in silico and in vitro assays have been developed for safety assessment in early drug discovery. These methods are usually validated using datasets of known drugs with large chemical diversity, while application to homologous series has been rarely explored. Here we report a case study about phospholipidosis (PLD) risk evaluation for a dataset of nine compounds, designed and synthesized to modulate the physico-chemical properties typical of cationic amphiphilic compounds (CADs), representing the main class of PLD inducers. Our aim was to investigate the effect of structure modification on PLD induction according to a number of standard in silico and in vitro methods. As a result, we found that different in silico methods lead to conflicting results when applied to our series of weak PLD inducers, thus the apparently easy-to-use definition of CADs requires special attention. Moreover, when weak inducers are tested in vitro, the revealed PLD effect may vary based on the purity grade of the tested compound and the features of the selected assay. Finally, we have shown that slight modifications on a chemical scaffold can have an impact on the PLD effect. This study also exemplifies that current in silico methods possibly overestimate the PLD induction effect of cationic amphiphilic compounds compared to the in vitro, with the risk of discarding promising compounds based on incorrect safety liabilities.

  DOI：

  10.1007/s00044-017-2093-5

文献信息

• Hypotensive Agents. IV.¹ Hydrogenated Dialkylaminoalkyl Isoindole Derivatives²
  作者：Leonard M. Rice、Charles H. Grogan、E. Emmet Reid

  DOI：10.1021/ja01116a010

  日期：1953.10
• Synthesis and phospholipidosis effect of a series of cationic amphiphilic compounds: a case study to evaluate in silico and in vitro assays
  作者：Susan Lepri、Aurora Valeri、Sandra Buratta、Martina Ceccarelli、Desirée Bartolini、Renzo Ruzziconi、Laura Goracci

  DOI：10.1007/s00044-017-2093-5

  日期：2018.2

  In recent years, a large number of in silico and in vitro assays have been developed for safety assessment in early drug discovery. These methods are usually validated using datasets of known drugs with large chemical diversity, while application to homologous series has been rarely explored. Here we report a case study about phospholipidosis (PLD) risk evaluation for a dataset of nine compounds, designed and synthesized to modulate the physico-chemical properties typical of cationic amphiphilic compounds (CADs), representing the main class of PLD inducers. Our aim was to investigate the effect of structure modification on PLD induction according to a number of standard in silico and in vitro methods. As a result, we found that different in silico methods lead to conflicting results when applied to our series of weak PLD inducers, thus the apparently easy-to-use definition of CADs requires special attention. Moreover, when weak inducers are tested in vitro, the revealed PLD effect may vary based on the purity grade of the tested compound and the features of the selected assay. Finally, we have shown that slight modifications on a chemical scaffold can have an impact on the PLD effect. This study also exemplifies that current in silico methods possibly overestimate the PLD induction effect of cationic amphiphilic compounds compared to the in vitro, with the risk of discarding promising compounds based on incorrect safety liabilities.