9-benzyl-β-carboline-3-carbohydrazide | 799821-70-8

• 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: 9-benzyl-β-carboline-3-carbohydrazide
• 英文别名: 9-benzyl-β-carboline-3-carboxylic acid hydrazide；9-Benzylpyrido[3,4-b]indole-3-carbohydrazide
• CAS: 799821-70-8
• 化学式: C₁₉H₁₆N₄O
• 分子量: 316.362
• InChiKey: SNVRIHZBXQOGDQ-UHFFFAOYSA-N

物化性质

• 熔点：
  209-211 °C(Solv: ethanol (64-17-5))
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-benzyl-β-carboline-3-carbohydrazide 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.67h， 以89%的产率得到3-azidocarbonyl-9-benzyl-β-carboline
  参考文献：
  名称：

  Design, synthesis and in vitro and in vivo antitumor activities of novel β-carboline derivatives

  摘要：

  To further our SAR study on the chemistry and antitumor activity/neurotoxicity of beta-carboline alkaloids. several series of beta-carboline derivatives with various substituents were designed and synthesized from the starting material L-tryptophan on the basis of harmine chemical structure. Cytotoxic activities of these compounds were investigated in vitro. The results showed that some beta-carboline derivatives had significant cytotoxic activities against human tumor cell lines. Among all the synthesized beta-carboline derivatives, the compounds 27, 28 and 32, having a benzyl substituent at both position-2 and 9, respectively, were found to be the most potent compounds with IC50 value lower than 50 mu M against all human tumor cell lines examined. Acute toxicities and antitumor activities of the selected beta-carboline derivatives in mice were also evaluated. The results demonstrated that a benzyl substituent at position-2 increased the antitumor activity as well as acute toxicity significantly. However an (ethoxycarbonyl)amino substituent at position-3 reduced the acute toxicity as well as antitumor activity remarkedly. These data suggested that (1) the antitumor potencies of beta-carboline derivatives were enhanced by the introduction of benzyl substituent into the position-2; (2) the acute toxicity of beta-carboline derivatives reduced dramatically by the introduction of an appropriate substituent into the position-3 and 9; (3) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs with significant antitumor activity and low toxicity. (c) 2005 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.04.008
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 氯化亚砜 、 hydrazine hydrate 、 sodium hydride 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 9-benzyl-β-carboline-3-carbohydrazide
  参考文献：
  名称：

  新型 N-酰基腙键连接的杂二价 β-咔啉作为潜在抗癌剂的设计、合成和生物学评价

  摘要：

  利用药效团杂交方法，我们设计并合成了一系列新的 28 种新型异二价 β-咔啉。评估了每种化合物对不同来源（鼠类和人）的五种癌细胞系（LLC、BGC-823、CT-26、Bel-7402 和 MCF-7）的体外细胞毒性潜力，目的是确定化合物的效力和选择性。化合物 8z 显示出抗肿瘤活性，半数最大抑制浓度 (IC50) 值为 9.9 ± 0.9、8.6 ± 1.4、6.2 ± 2.5、9.9 ± 0.5 和 5.7 ± 1.2 µM，对测试的五种癌细胞系。此外，使用鸡绒毛尿囊膜 (CAM) 体内模型研究了化合物 8z 对血管生成过程的影响。在 5 μM 的浓度下，化合物 8z 显示出对血管生成的积极影响。

  DOI：

  10.3390/molecules24162950

文献信息

• Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents
  作者：Chen、Guo、Ma、Chen、Fan、Zhang

  DOI：10.3390/molecules24162950

  日期：——

  Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z

  利用药效团杂交方法，我们设计并合成了一系列新的 28 种新型异二价 β-咔啉。评估了每种化合物对不同来源（鼠类和人）的五种癌细胞系（LLC、BGC-823、CT-26、Bel-7402 和 MCF-7）的体外细胞毒性潜力，目的是确定化合物的效力和选择性。化合物 8z 显示出抗肿瘤活性，半数最大抑制浓度 (IC50) 值为 9.9 ± 0.9、8.6 ± 1.4、6.2 ± 2.5、9.9 ± 0.5 和 5.7 ± 1.2 µM，对测试的五种癌细胞系。此外，使用鸡绒毛尿囊膜 (CAM) 体内模型研究了化合物 8z 对血管生成过程的影响。在 5 μM 的浓度下，化合物 8z 显示出对血管生成的积极影响。
• HARMINE DERIVATIVES, INTERMEDIATES USED IN THEIR PREPARATION, PREPARATION PROCESSES AND USE THEREOF
  申请人：Xinjiang Huashidan Pharmaceutical Research Co., Ltd.

  公开号：EP1634881B1

  公开（公告）日：2011-07-27
• The synthesis, structure and photoluminescent properties of solid-state green to yellow emitters based on β-carboline
  作者：Yi-Feng Sun、Zhi-Yong Chen、Ya-Ling Liu、Na Li、Ji-Kun Li、Hua-Can Song

  DOI：10.1016/j.dyepig.2012.06.002

  日期：2012.12

  A series of solid-state green to yellow emitters based on beta-carboline core were synthesized and characterized. The crystal structures of four of them were determined by single crystal X-ray diffraction analysis. The photoluminescent properties of beta-carbolines were examined in solution and in the solid state. It was found that these fluorophores were luminescent, having solid-state emission at wavelengths ranging from 505 to 582 nm, depending on structure. Significantly, two naphthalene-carboline hybrids exhibit strong green fluorescence emission both in solution and in crystalline state. However, two methoxyl-phenyl substituted beta-carboline derivative show intense green/yellow emission peaked at 540-582 nm, and display red-shifted by 40-82 nm with respect to the solution behavior. The experimental results demonstrated that the solid-state emission ranging from green to yellow can be readily tuned by simply varying molecular structure. The solid-state luminescent properties are highly dependent on the nature and position of the substituents and also on the molecular arrangements and the intermolecular interactions. (C) 2012 Elsevier Ltd. All rights reserved.
• Design, synthesis and in vitro and in vivo antitumor activities of novel β-carboline derivatives
  作者：R. Cao、H. Chen、W. Peng、Y. Ma、X. Hou、H. Guan、X. Liu、A. Xu

  DOI：10.1016/j.ejmech.2005.04.008

  日期：2005.10

  To further our SAR study on the chemistry and antitumor activity/neurotoxicity of beta-carboline alkaloids. several series of beta-carboline derivatives with various substituents were designed and synthesized from the starting material L-tryptophan on the basis of harmine chemical structure. Cytotoxic activities of these compounds were investigated in vitro. The results showed that some beta-carboline derivatives had significant cytotoxic activities against human tumor cell lines. Among all the synthesized beta-carboline derivatives, the compounds 27, 28 and 32, having a benzyl substituent at both position-2 and 9, respectively, were found to be the most potent compounds with IC50 value lower than 50 mu M against all human tumor cell lines examined. Acute toxicities and antitumor activities of the selected beta-carboline derivatives in mice were also evaluated. The results demonstrated that a benzyl substituent at position-2 increased the antitumor activity as well as acute toxicity significantly. However an (ethoxycarbonyl)amino substituent at position-3 reduced the acute toxicity as well as antitumor activity remarkedly. These data suggested that (1) the antitumor potencies of beta-carboline derivatives were enhanced by the introduction of benzyl substituent into the position-2; (2) the acute toxicity of beta-carboline derivatives reduced dramatically by the introduction of an appropriate substituent into the position-3 and 9; (3) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs with significant antitumor activity and low toxicity. (c) 2005 Elsevier SAS. All rights reserved.
• Molecular hybrid design, synthesis, in vitro and in vivo anticancer evaluation, and mechanism of action of N-acylhydrazone linked, heterobivalent β-carbolines
  作者：Liang Guo、Xiaofei Chen、Wei Chen、Qin Ma、Wenxi Fan、Jie Zhang、Bin Dai

  DOI：10.1016/j.bioorg.2020.103612

  日期：2020.3

  cytotoxic activity of the synthesized compounds was evaluated against normal EA.HY926 cells and five cancer cell lines: LLC (Lewis lung carcinoma), BGC-823 (gastric carcinoma), CT-26 (murine colon carcinoma), Bel-7402 (liver carcinoma), and MCF-7 (breast carcinoma). Compound 10e, with an IC50 value of 2.41 μM against EA.HY926 cells, was the most potent inhibitor. It showed cytotoxicity against all five

  设计了一系列由N-酰基hydr连接的异二价β-咔啉衍生物，并按九步反应顺序由1-色氨酸合成。该努力导致了高收率的异二价β-咔啉10a-t。目标化合物通过1H NMR，13C NMR和高分辨率质谱（HRMS）进行表征。评估了合成化合物对正常EA.HY926细胞和5种癌细胞系的体外细胞毒性活性：LLC（刘易斯肺癌），BGC-823（胃癌），CT-26（鼠结肠癌），Bel-7402 （肝癌）和MCF-7（乳腺癌）。化合物10e对EA.HY926细胞的IC50值为2.41μM，是最有效的抑制剂。它对鼠类和人类这五种不同来源的癌细胞系均显示出细胞毒性，IC50值为4.2±0。7至18.5±3.1μM。对结构-活性关系的研究表明，R9'-位对取代基的细胞毒性活性的影响遵循2,3,4,5,6-全氟苯基甲基> 4-氟苄基> 3-苯基丙基的趋势。还在小鼠中评估了所选化合物的抗肿瘤功效。化合物10e表现出有效