9-benzyl-1-methyl-9H-pyrido[3,4-b]indole

• 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-benzyl-1-methyl-9H-pyrido[3,4-b]indole
• 英文别名: 9-benzyl-1-methyl-β-carboline；9-Benzyl-1-methylpyrido[3,4-b]indole
• 化学式: C₁₉H₁₆N₂
• 分子量: 272.349
• InChiKey: RZYUJKCVRRJONE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 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-benzyl-1-methyl-9H-pyrido[3,4-b]indole 在 selenium(IV) oxide 、 sodium cyanoborohydride 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 1-[N-(2-diethylamino-ethyl)-aminomethyl]-9-benzyl-β-carboline
  参考文献：
  名称：

  Synthesis and biological evaluation of 1,9-disubstituted β-carbolines as potent DNA intercalating and cytotoxic agents

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.08.027
• 作为产物：
  描述：

  L-色氨酸 在 manganese(IV) oxide 、 硫酸 、 sodium hydride 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 9-benzyl-1-methyl-9H-pyrido[3,4-b]indole
  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

文献信息

• Multicomponent synthesis of novel β-carboline-fused imidazolium derivatives <i>via</i> the Mannich reaction: cytotoxicity, molecular docking, and mechanistic studies as angiogenesis inhibitors
  作者：Siyu Zhu、Xiaofei Chen、Wei Chen、Qin Ma、Meng Li、Wenxi Fan、Jie Zhang、Liang Guo

  DOI：10.1039/d1nj05471f

  日期：——

  In this paper, a novel series of β-carboline-fused imidazolium derivatives (3a–3v) were designed and synthesized based on the structures of fascaplysin and our reported novel compound HMD-272 (9-(3-phenylpropyl)-2-benzyl-β-carbolinium bromide). Evaluation of the cytotoxicity of 3a–3v was conducted using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in lung carcinoma (A549)

  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
• New β-carboline derivatives containing imidazolium as potential VEGFR2 inhibitors: synthesis, X-ray structure, antiproliferative evaluations, and molecular modeling
  作者：Ling Ma、Xiaofei Chen、Siyu Zhu、Wei Chen、Qin Ma、Wenxi Fan、Jie Zhang、Liang Guo

  DOI：10.1039/d2md00065b

  日期：——

  A series of new β-carboline derivatives containing an imidazolium moiety were designed and synthesized via the reaction of β-carboline-1-carboxaldehydes, acetyl chloride, primary amine, and formaldehyde. The antitumor activity of the synthesized compounds was examined against lung carcinoma (A549), gastric carcinoma (BGC-823), murine colon carcinoma (CT-26), liver carcinoma (Bel-7402) and breast carcinoma

  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
• Design, synthesis and in vitro cytotoxicity studies of novel β -carbolinium bromides
  作者：P.O. Venkataramana Reddy、Shriprada Mishra、Mukund P. Tantak、Kumar Nikhil、Rachna Sadana、Kavita Shah、Dalip Kumar

  DOI：10.1016/j.bmcl.2017.02.010

  日期：2017.3

  A series of novel beta-carbolinium bromides has been synthesized from easily accessible beta-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 161, 16o and 16s exhibited potent anticancer activity with IC50 values of <10 mu M against tested cancer cell lines. The most potent analogue 161 was broadly active against all the tested cancer cell lines (IC50 = 3.16-7.93 mu M). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 161 and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that a-carbolinium salts induce apoptosis in these cells. Additionally, the most potent beta-carbolines 161 and 16s were found to inhibit tubulin polymerization. (C) 2017 Elsevier Ltd. All rights reserved.
• Exploiting the Polypharmacology of ß-Carbolines to Disrupt <i>O. volvulus</i> Molting
  作者：Major Gooyit、Nancy Tricoche、Sacha Javor、Sara Lustigman、Kim D. Janda

  DOI：10.1021/ml500516r

  日期：2015.3.12

  Onchocerciasis is an infection caused by the filarial worm Onchocerca volvulus, which can eventually result in blindness. The lack of an effective macrofilaricide and the possible development of ivermectin-resistant strains of O. volvulus necessitate the, need for alternative treatment strategies. We have shown that targeting the L3-stagespecific chitinase OvCHT1 impairs the shedding of the filarial cuticle. In our continued efforts to discover OvCHT1 inhibitors, we identified the beta-carboline alkaloid scaffolding as a chitinase inhibitor that is capable of penetrating the worm cuticle. Herein, we disclose the rich polypharmacology of the beta-carboline class of compounds as an approach to abrogate the molting of the parasite and thus the initiation of infection in the human host.
• 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.