1-methyl-9-(3-phenylpropyl)-β-carboline

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-methyl-9-(3-phenylpropyl)-β-carboline
• 英文别名: 9-(3-phenylpropyl)-1-methyl-β-carboline；1-Methyl-9-(3-phenylpropyl)pyrido[3,4-b]indole
• 化学式: C₂₁H₂₀N₂
• 分子量: 300.403
• InChiKey: IGWFPOLFZKLMBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-methyl-9-(3-phenylpropyl)-β-carboline 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以68%的产率得到9-(3-phenylpropyl)-β-carboline-1-carboxaldehyde
  参考文献：
  名称：

  分子杂合设计，合成，体内外抗癌评估以及N-酰基hydr连接的异二价β-咔啉的作用机理。

  摘要：

  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

  DOI：

  10.1016/j.bioorg.2020.103612
• 作为产物：
  描述：

  L-色氨酸 在 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-methyl-9-(3-phenylpropyl)-β-carboline
  参考文献：
  名称：

  通过曼尼希反应多组分合成新型 β-咔啉融合咪唑衍生物：细胞毒性、分子对接和作为血管生成抑制剂的机制研究

  摘要：

  本文基于 fascaplysin 的结构和我们报道的新型化合物 HMD-272 (9-(3-phenylpropyl) -2 - benzyl -β-溴化碳）。在肺癌 (A549)、胃癌 (BGC-823) 中使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定法评估3a-3v的细胞毒性、鼠结肠癌 (CT-26)、肝癌 (Bel-7402) 和乳腺癌 (MCF-7) 细胞系。结果表明，大多数目标化合物对一种或多种癌细胞系表现出优异的活性，化合物3i、3j、3m、3p、3u和3v对测试的肿瘤细胞系表现出最高的细胞毒活性 (IC 50 < 10 μM)。对作用机制的初步研究表明，化合物3v可以以剂量依赖性方式显着抑制EA.HY926细胞管的形成。对初步作用机制的进一步研究表明，化合物3v在鸡绒毛尿囊膜 (CAM) 试验中具有明显的血管生成抑制作用。此外，为了了解化

  DOI：

  10.1039/d1nj05471f

文献信息

• 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
• 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.
• Synthesis and biological evaluation of 1,9-disubstituted β-carbolines as potent DNA intercalating and cytotoxic agents
  作者：Zhiyong Chen、Rihui Cao、Buxi Shi、Liang Guo、Jie Sun、Qin Ma、Wenxi Fan、Huacan Song

  DOI：10.1016/j.ejmech.2011.08.027

  日期：2011.10

  A series of novel 1,9-disubstituted beta-carbolines was designed, synthesized and evaluated as cytotoxic and DNA intercalating agents. Compounds 7b, 7c, 8b and 8c exhibited the most potent cytotoxic activities with IC50 values of lower than 20 mu M against ten human tumor cell lines. The results indicated that (1) the 3-chlorobenzyl and 3-phenylpropyl substituents in position-9 of beta-carboline nucleus were the suitable pharmacophoric group giving rise to significant antitumor agents; (2) the length of the alkylamino side chain moiety affected their cytotoxic potencies, and three CH2 units were more favorable. In addition, these compounds were found to exhibit remarkable DNA intercalating effects. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Synthesis and structure–activity relationships of N2-alkylated quaternary β-carbolines as novel antitumor agents
  作者：Guoxian Zhang、Rihui Cao、Liang Guo、Qin Ma、Wenxi Fan、Xuemei Chen、Jianru Li、Guang Shao、Liqin Qiu、Zhenghua Ren

  DOI：10.1016/j.ejmech.2013.04.031

  日期：2013.7

  A series of novel N-2-alkylated quaternary beta-carbolines was synthesized by modification of position-1, 2,7 and 9 of beta-carboline nucleus with various alkyl and arylated alkyl substituents, and their cytotoxic activities in vitro and antitumor potencies in mice were evaluated. Compound 3m was found to be the most potent antitumor agent. SARs analysis revealed that (1) the substituents in position-2 and 9 of beta-carboline nucleus played a vital role in modulation of antitumor activity; (2) the benzyl and 3-phenylpropyl substituents in position-2 and 9 of beta-carboline ring were the optimal substituents giving rise to significant antitumor agent. These compounds might be a novel promising class of antitumor agents with clinical development potential. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors
  作者：Wei Chen、Guoxian Zhang、Liang Guo、Wenxi Fan、Qin Ma、Xiaodong Zhang、Runlei Du、Rihui Cao

  DOI：10.1016/j.ejmech.2016.08.050

  日期：2016.11

  We have synthesized and evaluated a series of novel alkyl diamine linked bivalent beta-carbolines as potent angiogenesis inhibitors. The results demonstrated that most bivalent beta-carbolines exhibited significant antiproliferative effects against human umbilical vein cell lines EA.HY926. Compound 4m was found to be the most potent antiproliferative agent with IC50 value of 2.16 mu M against EA.HY926 cell lines. Mechanism investigations revealed that compound 4m could significantly inhibit EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover, compound 4m also showed obvious angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was more potent than the reference drug Endostar. The bivalent beta-carbolines might be served as candidates for the development of vascular targeting antitumor drugs. (C) 2016 Elsevier Masson SAS. All rights reserved.