7-methoxy-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: 7-methoxy-9-n-butyl-1-methyl-β-carboline
• 英文别名: N-butyl harmine；9-butylharmine；7-methoxyl-9-n-butyl-1-methyl-β-carboline；N-butylharmine；9-butyl-7-methoxy-1-methylpyrido[3,4-b]indole
• 化学式: C₁₇H₂₀N₂O
• 分子量: 268.359
• InChiKey: ZTHNVHJIFDQKKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-methoxy-9-n-butyl-1-methyl-β-carboline 在 氢溴酸 、 sodium hydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 9-Butyl-1-methyl-7-[(2,3,4,5,6-pentafluorophenyl)methoxy]pyrido[3,4-b]indole
  参考文献：
  名称：

  Synthesis and structure–activity relationships of harmine derivatives as potential antitumor agents

  摘要：

  Harmine, a naturally occurring beta-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of beta-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.11.045
• 作为产物：
  描述：

  四氢骆驼蓬碱 在 5%-palladium/activated carbon 、 sodium hydride 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 7-methoxy-9-n-butyl-1-methyl-β-carboline
  参考文献：
  名称：

  N 9取代的香豆素衍生物作为潜在抗癌药的合成及生物学评价

  摘要：

  合成了一系列N 9取代的harmine衍生物，并评估了它们对一组癌细胞系的抗癌活性，它们的凋亡诱导作用以及它们的细胞周期效应。结果表明，N 9取代的甜菜碱衍生物具有抗癌作用。尤其是N 9-卤代烷基衍生物9a - 9c和N 9-酰基氨基甜菜碱衍生物11c和11d，其IC 50为值小于1μM的抗A-549和/或MCF-7细胞系的效力比阿霉素强。此外，结构-活性关系（SARs）表明，在甜菜碱的N 9位引入卤代烷基或苯磺酰基可以显着提高抗癌活性。活性最高的化合物（11d）导致细胞周期停滞在G2 / M期，并以剂量​​依赖性方式诱导细胞凋亡。

  DOI：

  10.1016/j.bmcl.2016.06.087

文献信息

• Design, Synthesis, and Antifungal Activity of Novel Aryl-1,2,3-Triazole-β-Carboline Hybrids
  作者：Xin-Yu Huo、Liang Guo、Xiao-Fei Chen、Yue-Ting Zhou、Jie Zhang、Xiao-Qiang Han、Bin Dai

  DOI：10.3390/molecules23061344

  日期：——

  were evaluated in vitro for their antifungal activity against Rhizoctorzia solani, Fusarium oxysporum, Botrytis cinerea Pers., sunflower sclerotinia rot, and rape sclerotinia rot by mycelia growth inhibition assay at 50 μg/mL. The antifungal evaluation of the novel hybrids showed that, among the tested compounds, 5a, 5b, 5c, and 9b showed good antifungal activity against sunflower sclerotinia rot.

  铜催化叠氮化物和末端炔环加成反应，即“点击化学”，为制备l,4-二取代-l,2,3-三唑提供了一种新的、便捷的方法。在这项工作中，2-吡咯碳亚胺基Cu(II)配合物被建立为芳基硼酸和叠氮化钠(NaN₃)与末端炔烃在乙醇中在室温至50°下进行三组分1,3-偶极环加成反应的有效催化剂。合成了C，1,4-二取代的1,2,3-三唑。按照优化方案，设计并合成了两个系列的新型芳基-1,2,3-三唑-β-咔啉杂化物，并通过 1H NMR、13C NMR 和高分辨率质谱（HRMS）对化学结构进行了表征。 ）。通过菌丝体生长抑制测定，在体外评估了所有目标化合物对立枯丝核菌、尖孢镰刀菌、灰葡萄孢、向日葵菌核病和油菜菌核病的抗真菌活性。对新型杂种的抗真菌评价表明，受试化合物中，5a、5b、5c和9b对向日葵菌核腐病表现出良好的抗真菌活性。具体而言，化合物9b对所有测试的真菌均表现出高广谱杀菌作用，抑制率分别为58
• Synthesis and structure-activity relationships of asymmetric dimeric β-carboline derivatives as potential antitumor agents
  作者：Liang Guo、Wei Chen、Rihui Cao、Wenxi Fan、Qin Ma、Jie Zhang、Bin Dai

  DOI：10.1016/j.ejmech.2018.02.003

  日期：2018.3

  series of newly asymmetric dimeric β-carbolines with a spacer of 4–6 methylene units between the indole nitrogen and the harmine oxygen were synthesized. Structures of all the novel synthesized compounds were confirmed by their spectral and analytical studies. All of the synthesized compounds were screened for their in vitro cytotoxic activity against nine cancer cell lines. The results revealed that

  合成了一系列新的不对称的二聚β-咔啉，它们在吲哚氮和氨苄基氧之间具有一个4-6个亚甲基单元的间隔。通过光谱和分析研究证实了所有新型合成化合物的结构。筛选所有合成的化合物对九种癌细胞系的体外细胞毒活性。结果表明，化合物7c，7o和7s对测试的肿瘤细胞系表现出最高的细胞毒活性，IC 50值小于20μM。还评估了所选化合物在小鼠中的急性毒性和抗肿瘤功效，并且化合物7o表现出有效的抗肿瘤活性，肿瘤抑制率超过40％。伤口愈合试验显示了HT-29细胞运动性的特定损伤，这提示了化合物7o的抗转移潜力。此外，化合物7o在鸡绒膜尿囊膜（CAM）分析中具有明显的血管生成抑制作用。初步的结构-活性关系（SAR）分析表明：（1）吲哚环N 9位的3-苯基丙基取代基是最合适的产生有效细胞毒性剂的基团；（2）间隔物长度影响抗肿瘤能力，并且四个亚甲基单元是更有利的。
• Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives
  作者：Rihui Cao、Qi Chen、Xuerui Hou、Hongsheng Chen、Huaji Guan、Yan Ma、Wenlie Peng、Anlong Xu

  DOI：10.1016/j.bmc.2004.06.038

  日期：2004.9

  A series of novel 9-substituted beta-carboline derivatives was synthesized from harmine and l-tryptophan, respectively. Cytotoxic activities of these compounds in vitro were investigated. The results showed that most compounds of 9-substituted beta-carboline derivatives had more remarkable cytotoxic activities in vitro than their corresponding parent compounds. Acute toxicities and antitumor effects

  分别从甜蜜素和色氨酸合成了一系列新颖的9-取代的β-咔啉衍生物。研究了这些化合物在体外的细胞毒活性。结果表明，大多数9-取代的β-咔啉衍生物的化合物在体外具有比其相应母体化合物更显着的细胞毒活性。还检查了选定的β-咔啉衍生物在小鼠中的急性毒性和抗肿瘤作用。结果表明，位置9处的短烷基或苄基取代基显着提高了抗肿瘤活性，位置3处的乙氧羰基或羧基取代基显着降低了这些β-咔啉衍生物的急性毒性和神经毒性。而且，与其他化合物相比，在第3位具有烷氧基羰基或羧基取代基且在第9位具有短烷基或苄基取代基的化合物均表现出更显着的抗肿瘤活性以及较低的急性毒性和神经毒性。发现分别在第9位和第3位具有正丁基和羧基取代基的化合物8c具有最高的抗肿瘤作用和最低的急性毒性和神经毒性。这些数据表明：（1）β-咔啉衍生物第9位和第3位的适当取代基可能在确定其增强的抗肿瘤活性以及降低的急性毒性和神经毒性作用方面起着至关重要的作用；
• 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。
• 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。