2-methyl-9-[9-(2-methyl-1,2,3,4-tetrahydro-β-carboline-9-yl)nonyl]-1,2,3,4-tetrahydro-β-carboline | 1225056-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-methyl-9-[9-(2-methyl-1,2,3,4-tetrahydro-β-carboline-9-yl)nonyl]-1,2,3,4-tetrahydro-β-carboline
• 英文别名: 2-Methyl-9-[9-(2-methyl-1,2,3,4-tetrahydro-beta-carboline-9-yl)nonyl]-1,2,3,4-tetrahydro-beta-carboline；2-methyl-9-[9-(2-methyl-3,4-dihydro-1H-pyrido[3,4-b]indol-9-yl)nonyl]-3,4-dihydro-1H-pyrido[3,4-b]indole
• CAS: 1225056-76-7
• 化学式: C₃₃H₄₄N₄
• 分子量: 496.739
• InChiKey: JADBPNYNHZGHDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  16.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-methyl-9-[9-(2-methyl-β-carboline-9-yl)nonyl]-β-carboline-2-ium diiodide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以70%的产率得到2-methyl-9-[9-(2-methyl-1,2,3,4-tetrahydro-β-carboline-9-yl)nonyl]-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Bivalent β-Carbolines as Potential Multitarget Anti-Alzheimer Agents

  摘要：

  Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with multifactorial causes that requires multitargeted treatment. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) improve cholinergic signaling in the central nervous system and thus AChE inhibitors are well established in the therapy of AD to improve memory disturbances and other cognitive symptoms. On the other hand, AD patients benefit from reduction of pathologic glutamate-induced, Ca2+-mediated excitotoxicity by the N-methyl-D-aspartate receptor (NR) antagonist memantine. New drugs that simultaneously affect both cholinergic transmission and glutamate-induced excitotoxicity may further improve AD treatment. While connecting beta-carboline units by alkylene spacers in two different series of compounds and subsequent evaluation of their AChE/BChE-inhibitory potential, we found that several of these bivalent beta-carbolines were potent NR blockers. The most promising compound was a N-9-homobivalent beta-carboline with a nonylene spacer, which displayed IC50 values of 0.5 nM for AChE, 5.7 nM for BChE, and 1.4 mu M for NR, respectively.

  DOI：

  10.1021/jm1000024

文献信息

• BIS-B-CARBOLINE COMPOUND AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：XINJIANG HUASHIDAN PHAR MACEUTICAL RESEARCH CO., LTD

  公开号：US20160039845A1

  公开（公告）日：2016-02-11

  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-咔唑化合物及其制备方法、药物组合物及其用途。其中，描述了双β-咔唑化合物及其药物盐的一般式I，双β-咔唑化合物是通过β-咔唑中间体和二卤代烷的缩合反应制备而成。本发明还公开了一种药物组合物，包括一定剂量的公式I所示的双β-咔唑化合物和药学上可接受的载体，并且公开了将双β-咔唑化合物用于制备对肿瘤具有抗药性的药物，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。
• Bis-β-carboline compound and preparation method, pharmaceutical composition and use thereof
  申请人：XINJIANG HUASHIDAN PHARMACEUTICAL RESEARCH CO., LTD.

  公开号：US10011614B2

  公开（公告）日：2018-07-03

  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 tumors 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，双-β-咔啉化合物及其药用盐描述为通式 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。
• Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders
  作者：Robert Otto、Robert Penzis、Friedemann Gaube、Oliver Adolph、Karl J. Föhr、Paul Warncke、Dina Robaa、Dorothea Appenroth、Christian Fleck、Christoph Enzensperger、Jochen Lehmann、Thomas Winckler

  DOI：10.1021/acs.jmedchem.5b00958

  日期：2015.8.27

  Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent gamma-carbolinium salts as potent inihitors of both cholinesterases, N-methyl-D-aspartate receptors, and monoamine oxidases. Homobivalent gamma-carbolines displayed similar structure activity relationships on all tested targets and may present promising designed multiple ligands for the treatment of neurodegenerative disorders.