ethyl 9-benzyl-1-methyl-9H-pyrido[3,4-b]indole-3-carboxylate | 142272-78-4

• 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: ethyl 9-benzyl-1-methyl-9H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: ethyl 9-benzyl-1-methyl-β-carboline-3-carboxylate；Ethyl 9-benzyl-1-methyl-beta-carboline-3-carboxylate；ethyl 9-benzyl-1-methylpyrido[3,4-b]indole-3-carboxylate
• CAS: 142272-78-4
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: DQUCJSXWLXYNAO-UHFFFAOYSA-N

物化性质

• 熔点：
  155-156 °C
• 沸点：
  499.1±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 9-benzyl-1-methyl-9H-pyrido[3,4-b]indole-3-carboxylate 在 锂硼氢 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 3-hydroxymethyl-9-benzyl-1-methyl-β-carboline
  参考文献：
  名称：

  Synthesis and preliminary evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors

  摘要：

  一系列新颖的双价β-咔啉类化合物被合成并评估为有效的血管生成抑制剂。

  DOI：

  10.1039/c6md00360e
• 作为产物：
  描述：

  L-色氨酸 在 氯化亚砜 、 sodium hydride 、 sulfur 、 溶剂黄146 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 15.0h， 生成 ethyl 9-benzyl-1-methyl-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Synthesis and preliminary evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors

  摘要：

  一系列新颖的双价β-咔啉类化合物被合成并评估为有效的血管生成抑制剂。

  DOI：

  10.1039/c6md00360e

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 of β-carboline derivatives as DNA-targeting antitumor agents
  作者：Huaji Guan、Hongsheng Chen、Wenlie Peng、Yan Ma、Rihui Cao、Xiaodong Liu、Anlong Xu

  DOI：10.1016/j.ejmech.2006.05.004

  日期：2006.10

  This research studied the structure-activity relationship of beta-carboline derivatives as antitumor agents, in which 41 synthesized compounds and their cytotoxicity to tumor and normal cell lines were assayed. It was proved that substituent in position-9 of the beta-carboline ring could reinforce the DNA intercalating ability and consequently cytotoxicity to tumor cell lines, and the amidation of

  本研究研究了β-咔啉衍生物作为抗肿瘤剂的构效关系，分析了41种合成化合物及其对肿瘤和正常细胞系的细胞毒性。事实证明，β-咔啉环第9位的取代基可增强DNA的插入能力，从而增强对肿瘤细胞的细胞毒性，而靶向第3位侧链的DNA末端的氨基酰胺化则会削弱这些化合物的DNA嵌入活性，从而引发了对肿瘤细胞系而不是正常细胞系的细胞毒选择性。此外，这些化合物引起的S和G2-M阻滞证实，它们可以靶向DNA并导致Hela细胞中的DNA破坏。简而言之，
• Harmine derivatives, intermediates used in their preparations, preparation processes and use therefo
  申请人：Wu Jialin

  公开号：US20090227619A1

  公开（公告）日：2009-09-10

  This invention relates to compounds of general formula (I), wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the specification; intermediates used in their preparation, preparation processes and use thereof. The present invention produces new harmine derivatives with enhanced antitumour activity and lower nervous system toxicity by structurally modification of the parent structure of β-carboline of harmines at position 1, 2, 3, 7 and 9. The compounds of the present invention can be prepared easily with high yield. They can be used in manufacture of a variety of antitumour medicines and medicines used in treatment of tumour diseases in combination of light or radiation therapy.

  本发明涉及一般式（I）的化合物，其中R1、R2、R3、R4和R5如规范中所定义；用于它们的制备的中间体，制备方法和使用。本发明通过在β-噻吩类似物的母体结构的1、2、3、7和9位进行结构修饰，产生具有增强抗肿瘤活性和较低神经系统毒性的新的harmine衍生物。本发明的化合物可以轻松高产制备。它们可以用于制造各种抗肿瘤药物和用于结合光或放射治疗治疗肿瘤疾病的药物。
• Harmine derivatives, intermediates used in their preparations, preparation processes and use thereof
  申请人：Wu Jialin

  公开号：US08772311B2

  公开（公告）日：2014-07-08

  This invention relates to compounds of general formula (I), wherein R1, R2, R3, R4 and R5 are as defined in the specification; intermediates used in their preparation, preparation processes and use thereof. The present invention produces new harmine derivatives with enhanced antitumor activity and lower nervous system toxicity by structurally modification of the parent structure of β-carboline of harmines at position 1, 2, 3, 7 and 9. The compounds of the present invention can be prepared easily with high yield. They can be used in manufacture of a variety of antitumor medicines and medicines used in treatment of tumor diseases in combination of light or radiation therapy.

  本发明涉及通式（I）的化合物，其中R1，R2，R3，R4和R5如规范中所定义；用于其制备的中间体，制备过程以及其用途。本发明通过在β-咔啉毒素的母体结构的1、2、3、7和9位进行结构修饰，产生具有增强的抗肿瘤活性和较低的神经系统毒性的新的哈曼衍生物。本发明的化合物可以轻松地高产制备。它们可以用于制造各种抗肿瘤药物和联合光或放射治疗用于治疗肿瘤疾病的药物。
• Design, synthesis and pharmacological evaluation of β-carboline derivatives as potential antitumor agent via targeting autophagy
  作者：Jingsheng Ao、Feng Zeng、Longhao Wang、Liqin Qiu、Rihui Cao、Xiangpan Li

  DOI：10.1016/j.ejmech.2022.114955

  日期：2023.1

  A series of novel β-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. Among them, compound 6g showed the most potent antiproliferative activity against the 786–0, HT-29 and 22RV1 cell lines with IC50 values of 2.71, 2.02, and 3.86 μM, respectively. The antitumor efficiency of compound 6g in vivo was also evaluated, and the results revealed that compound 6g

  设计、合成并评估了一系列新型 β-咔啉衍生物作为潜在的抗癌药物。其中，化合物6g对 786-0、HT-29 和 22RV1 细胞系表现出最强的抗增殖活性，IC 50值分别为 2.71、2.02 和 3.86 μM。还评估了化合物6g 在体内的抗肿瘤效率，结果显示化合物6g在小鼠结直肠癌同种移植模型中显着抑制肿瘤发展并减轻肿瘤重量。进一步研究作用机制表明，化合物6g通过刺激 ATG5/ATG7 依赖性自噬途径抑制 HCT116 细胞生长。这些分子可能作为进一步开发结直肠癌治疗药物的候选分子。