N-[2-(7-chloro-1H-indol-3-yl)ethyl]formamide | 1355078-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[2-(7-chloro-1H-indol-3-yl)ethyl]formamide
• CAS: 1355078-08-8
• 化学式: C₁₁H₁₁ClN₂O
• 分子量: 222.674
• InChiKey: NRFYNKNLUALBCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-[2-(7-chloro-1H-indol-3-yl)ethyl]formamide 在 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 8-chloro-4,9-dihydro-3H-pyrido[3,4-b] indole
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m
• 作为产物：
  描述：

  2-(7-氯-1H-吲哚-3-基)乙胺 、 甲酸乙酯 反应 6.0h， 生成 N-[2-(7-chloro-1H-indol-3-yl)ethyl]formamide
  参考文献：
  名称：

  New Tricks for an Old Natural Product: Discovery of Highly Potent Evodiamine Derivatives as Novel Antitumor Agents by Systemic Structure–Activity Relationship Analysis and Biological Evaluations

  摘要：

  Evodiamine is a quinazolinocarboline alkaloid isolated from the fruits of traditional Chinese herb Evodiae fructus. Previously, we identified N13-substituted evodiamine derivatives as potent topoisomerase I inhibitors by structure-based virtual screening and lead optimization. Herein, a library of novel evodiamine derivatives bearing various substitutions or modified scaffold were synthesized. Among them, a number of evodiamine derivatives showed substantial increase of the antitumor activity, with GI(50) values lower than 3 nM. Moreover, these highly potent compounds can effectively induce the apoptosis of A549 cells. Interestingly, further computational target prediction calculations in combination with biological assays confirmed that the evodiamine derivatives acted by dual inhibition of topoisomerases I and II. Moreover, several hydroxyl derivatives, such as 10-hydroxyl evodiamine (10j) and 3-amino-10-hydroxyl evodiamine (18g), also showed good in vivo antitumor efficacy and low toxicity at the dose of 1 mg/kg or 2 mg/kg. They represent promising candidates for the development of novel antitumor agents.

  DOI：

  10.1021/jm300605m

文献信息

• Visible-Light-Induced Trifluoromethylation of Isonitrile-Substituted Indole Derivatives: Access to 1-(Trifluoromethyl)-4,9-dihydro-3<i>H</i>-pyrido[3,4-b]indole and<i>β</i>-Carboline Derivatives
  作者：Jiaxin Liu、Longhai Li、Liuzhu Yu、Lisha Tang、Qin Chen、Min Shi

  DOI：10.1002/adsc.201800568

  日期：2018.8.6

  visible‐light‐induced trifluoromethylation of isonitrile‐substituted indole derivatives has been developed from the reaction of isonitrile‐substituted indoles with Togni II reagent, affording 1‐(trifluoromethyl)‐4,9‐dihydro‐3H‐pyrido[3,4‐b]indoles in moderate to good yields. The further transformations to β‐carboline derivatives and a harmacine derivative have been performed, demonstrating the potential synthetic

  的可见光诱导的异腈基取代的吲哚衍生物的三氟甲基化已经从与TOGNI II试剂异腈取代的吲哚的反应研制，得到1-（三氟甲基）-4,9-二氢-3- ħ -吡啶并[3,4 ‐b]吲哚产量中等至良好。已经进行了向β-咔啉衍生物和harmacine衍生物的进一步转化，证明了该方法的潜在合成效用。一项初步的生物学研究表明，含有CF 3的harmine类似物可显着刺激胰高血糖素样肽1（GLP-1）的分泌，表明糖尿病的治疗有所改善。