9-n-butyl-1-methyl-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: 9-n-butyl-1-methyl-β-carboline
• 英文别名: 9-Butyl-1-methylpyrido[3,4-b]indole
• 化学式: C₁₆H₁₈N₂
• 分子量: 238.332
• InChiKey: YTEIPPQHWOWURI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  9-n-butyl-1-methyl-β-carboline 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以65%的产率得到9-butyl-9H-pyrido[3,4-b]indole-1-carbaldehyde
  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 manganese(IV) oxide 、 硫酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 9-n-butyl-1-methyl-β-carboline
  参考文献：
  名称：

  含有咪唑铵作为潜在 VEGFR2 抑制剂的新型 β-卡博林衍生物：合成、X 射线结构、抗增殖评价和分子建模

  摘要：

  通过 β-咔唑-1-甲醛、乙酰氯、伯胺和甲醛的反应，设计合成了一系列含有咪唑鎓部分的新型 β-咔啉衍生物。检测合成化合物对肺癌 （A549） 、胃癌 （BGC-823） 、小鼠结肠癌 （CT-26）、肝癌 （Bel-7402） 和乳腺癌 （MCF-7） 细胞的抗肿瘤活性。结果表明，大多数化合物表现出显着的抗增殖活性，在某些情况下大于顺铂，并且发现化合物 3z 是针对 A549、BGC823、CT-26、Bel-7402 和 MCF-7 细胞系最有效的抗增殖剂，IC50 值为 2.7 ± 0.4、2.7 ± 0.6、2.4 ± 0.2、3.2 ± 0.2 和 5.6 ± 0.3 μM， 分别。结合良好的体外效能，还评估了所选化合物在小鼠中的抗肿瘤疗效。化合物 3z 在肉瘤 180 模型中表现出有效的抗肿瘤活性，肿瘤抑制率为 48.6%。对作用机制的初步研究表明，化合物 3z 可以以剂量依赖性方式显着抑制

  DOI：

  10.1039/d2md00065b

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
• BIS- -CARBOLINE COMPOUND AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：Xinjiang Huashidan Pharmaceutical Research Co., Ltd.

  公开号：EP2924042A1

  公开（公告）日：2015-09-30

  Disclosed in the present invention are a bis-β-carboline compound and a preparation method, a pharmaceutical composition and the use thereof. In particular, the bis-β-carboline compound and a pharmaceutical salt thereof are described as general formula I, and the bis-β-carboline compound is prepared through the condensation of β-carboline intermediate and dihaloalkane. Also disclosed in the present invention are a pharmaceutical composition comprising an effective dose of the bis-β-carboline compound as shown in formula I and a pharmaceutically acceptable carrier, and the use of the bis-β-carboline compound in preparing drugs resistant to tumours such as melanoma, stomach cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral epidermoid carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostate cancer, and colon cancer.

  本发明公开了一种双-β-咔啉化合物及其制备方法、药物组合物和用途。其中，所述双-β-咔啉化合物及其药物盐为通式Ⅰ，双-β-咔啉化合物是通过β-咔啉中间体和二卤代烷烃缩合制备的。本发明还公开了一种药物组合物，该组合物包含有效剂量的式 I 所示的双-β-咔啉化合物和药学上可接受的载体，以及双-β-咔啉化合物在制备抗肿瘤药物中的用途，如黑色素瘤、胃癌、肺癌、乳腺癌、肾癌、肝癌、口腔表皮癌、宫颈癌、卵巢癌、胰腺癌、前列腺癌和结肠癌。
• 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 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.