9-[5-(β-carboline-9-yl)pentyl]-β-carboline | 1225056-70-1

• 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: 9-[5-(β-carboline-9-yl)pentyl]-β-carboline
• 英文别名: 1,5-bis(β-carboline-9-yl)pentane；9-[5-(beta-Carboline-9-yl)pentyl]-beta-carboline；9-(5-pyrido[3,4-b]indol-9-ylpentyl)pyrido[3,4-b]indole
• CAS: 1225056-70-1
• 化学式: C₂₇H₂₄N₄
• 分子量: 404.514
• InChiKey: MRZCXQWEBCLSNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  35.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-[5-(β-carboline-9-yl)pentyl]-β-carboline 、 碘甲烷 以 丙酮 为溶剂， 反应 24.0h， 以97%的产率得到2-methyl-9-[5-(2-methyl-β-carboline-9-yl)pentyl]-β-carboline-2-ium diiodide
  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
• 作为产物：
  描述：

  1,5-二溴戊烷 、 9H-吡啶[3,4-b]吲哚 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以54%的产率得到9-[5-(β-carboline-9-yl)pentyl]-β-carboline
  参考文献：
  名称：

  Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent β-carbolines

  摘要：

  A series of bivalent beta-carbolines with a spacer of three to ten methylene units between the indole nitrogen was synthesized and evaluated as antitumor agents. The results demonstrated that compounds 18c, 21b, 25a and 31b exhibited strong cytotoxic activities with IC50 value of lower than 20 mu M against four tumor cell lines. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 18b, 21b, 26a and 31b exhibited potent antitumor activities with tumor inhibition rate of over 40% in animal models. Preliminary structure-activity relationships analysis indicated that (1) the spacer length affected antitumor potencies, and four to six methylene units were more favorable; (2) the introduction of appropriate substituent into position-1 of beta-carboline facilitated antitumor potencies. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.11.033

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。
• Bivalent β-Carbolines as Potential Multitarget Anti-Alzheimer Agents
  作者：Yvonne Rook、Kai-Uwe Schmidtke、Friedemann Gaube、Dirk Schepmann、Bernhard Wünsch、Jörg Heilmann、Jochen Lehmann、Thomas Winckler

  DOI：10.1021/jm1000024

  日期：2010.5.13

  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.
• Design, synthesis and in vitro and in vivo antitumor activities of novel bivalent β-carbolines
  作者：Buxi Shi、Rihui Cao、Wenxi Fan、Liang Guo、Qin Ma、Xuemei Chen、Guoxian Zhang、Liqin Qiu、Huacan Song

  DOI：10.1016/j.ejmech.2012.11.033

  日期：2013.2

  A series of bivalent beta-carbolines with a spacer of three to ten methylene units between the indole nitrogen was synthesized and evaluated as antitumor agents. The results demonstrated that compounds 18c, 21b, 25a and 31b exhibited strong cytotoxic activities with IC50 value of lower than 20 mu M against four tumor cell lines. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 18b, 21b, 26a and 31b exhibited potent antitumor activities with tumor inhibition rate of over 40% in animal models. Preliminary structure-activity relationships analysis indicated that (1) the spacer length affected antitumor potencies, and four to six methylene units were more favorable; (2) the introduction of appropriate substituent into position-1 of beta-carboline facilitated antitumor potencies. (C) 2012 Elsevier Masson SAS. All rights reserved.