1-ethyl-1H-indol-7-amine

• 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: 1-ethyl-1H-indol-7-amine
• 英文别名: 1-Ethyl-1H-indol-7-amine；1-ethylindol-7-amine
• 化学式: C₁₀H₁₂N₂
• 分子量: 160.219
• InChiKey: SIBHOCWKSAJSEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  31
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-ethyl-1H-indol-7-amine 、 苯甲酰乙酸乙酯 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以44.3%的产率得到ethyl 3-(1-ethyl-1H-indol-7-ylamino)-3-phenylacrylate
  参考文献：
  名称：

  Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs

  摘要：

  Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI(50) values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial. transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of beta-tubulin. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.11.038
• 作为产物：
  描述：

  7-硝基吲哚 在 sodium hydride 、 氯化铵 、 锌 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.17h， 生成 1-ethyl-1H-indol-7-amine
  参考文献：
  名称：

  [EN] NAPHTHYRIDINONE COMPOUNDS AS JAK2 V617F INHIBITORS
  [FR] COMPOSÉS NAPHTYRIDINONE EN TANT QU'INHIBITEURS DE JAK2 V617F

  摘要：

  本申请提供了一种能调节JAK2的V617F变体活性的萘啶酮化合物，可用于治疗包括癌症在内的各种疾病。

  公开号：

  WO2021257857A1

文献信息

• [EN] NAPHTHYRIDINONE COMPOUNDS AS JAK2 V617F INHIBITORS<br/>[FR] COMPOSÉS NAPHTYRIDINONE EN TANT QU'INHIBITEURS DE JAK2 V617F
  申请人：INCYTE CORP

  公开号：WO2021257857A1

  公开（公告）日：2021-12-23

  The present application provides naphthyridinone compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.

  本申请提供了一种能调节JAK2的V617F变体活性的萘啶酮化合物，可用于治疗包括癌症在内的各种疾病。
• Discovery of Potent Succinate-Ubiquinone Oxidoreductase Inhibitors via Pharmacophore-linked Fragment Virtual Screening Approach
  作者：Li Xiong、Xiao-Lei Zhu、Hua-Wei Gao、Yu Fu、Sheng-Quan Hu、Li-Na Jiang、Wen-Chao Yang、Guang-Fu Yang

  DOI：10.1021/acs.jafc.6b00325

  日期：2016.6.22

  Succinate-ubiquinone oxidoreductase (SQR) is an attractive target for fungicide discovery. Herein, we report the discovery of novel SQR inhibitors using a pharmacophore-linked fragment virtual screening approach, a new drug design method developed in our laboratory. Among newly designed compounds, compound 9s was identified as the most potent inhibitor with a value of 34 nM against porcine SQR, displaying approximately 10-fold higher potency than that of the commercial control penthiopyrad. Further inhibitory kinetics studies revealed that compound 9s is a noncompetitive inhibitor with respect to the substrate cytochrome c and DCIP. Interestingly, compounds 8a, 9h, 9j, and 9k exhibited good in vivo preventive effects against Rhizoctonia solani. The results obtained from molecular modeling showed that the orientation of the R-2 group had a significant effect on binding with the protein.
• NAPHTHYRIDINONE COMPOUNDS AS JAK2 V617F INHIBITORS
  申请人：Incyte Corporation

  公开号：US20210395251A1

  公开（公告）日：2021-12-23

  The present application provides naphthyridinone compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.
• Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs
  作者：Roberta Bortolozzi、Elena Mattiuzzo、Matteo Dal Pra、Mattia Sturlese、Stefano Moro、Ernest Hamel、Davide Carta、Giampietro Viola、Maria Grazia Ferlin

  DOI：10.1016/j.ejmech.2017.11.038

  日期：2018.1

  Earlier studies had confirmed that the 7-phenylpyrroloquinolinone (7-PPyQ) nucleus was an important scaffold for new chemotherapeutic drugs targeting microtubules. For wide-ranging SARs, a series of derivatives were synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-PPyQ 31, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Of the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI(50) values) was observed with 21 and 24, both more potent than 31, in both leukemic and solid tumor cell lines. Neither compound 21 nor 24 induced significant cell death in normal human lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 24 was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial. transmembrane potential and production of reactive oxygen species, indicating that cells treated with the compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot analysis revealed that compound 24 even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, molecular docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of beta-tubulin. (C) 2017 Elsevier Masson SAS. All rights reserved.