9-benzyl-1-methyl-β-carboline-3-carboxylic acid

• 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-β-carboline-3-carboxylic acid
• 英文别名: 9-Benzyl-1-methylpyrido[3,4-b]indole-3-carboxylic acid
• 化学式: C₂₀H₁₆N₂O₂
• 分子量: 316.359
• InChiKey: OXQFEHFDELROSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-benzyl-1-methyl-β-carboline-3-carboxylic acid 、 1,5-二溴戊烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以68%的产率得到1,5-bis(9-benzyl-1-methyl-β-carboline-3-carboxylic acid)pentanediyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of novel bivalent β-carbolines as potential antitumor agents

  摘要：

  一系列具有3-羧基氧之间间隔的双价β-咔啉类化合物被合成，并评估了它们的体外细胞毒活性和体内抗肿瘤效果。化合物22对小鼠Lewis肺癌表现出强效的抗肿瘤活性，肿瘤抑制率为64.2%。

  DOI：

  10.1039/c4md00098f
• 作为产物：
  描述：

  1-甲基-9H-吡啶并[3,4-b]吲哚-3-羧酸乙酯 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 9-benzyl-1-methyl-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives

  摘要：

  A series of novel 1,3-bisubstituted and 1, 3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material L-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1,3-bisubstituted compounds. Among all the synthesized 1,3,9-trisubstituted P-carboline derivatives, the compounds with a methyl substituent at position-1 displayed more potent cytotoxic activities, furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a pentafluorobenzyl at position-9, respectively, was found to be the most potent compounds of this series with IC50 value of 4 uM against BGC-823 cell lines. These data suggested that (1) the cytotoxic potencies of beta-carboline derivatives were enhanced by the introduction of appropriate substituents into position-1 and position-9 in beta-carboline; (2) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs; (3) the methyl substituent at position-1, the pentafluorobenzyl group at position-9 and the ethoxycarbonyl substituent at position-3 were the optimal combination for the improvement of cytotoxic activity of the P-carboline derivatives. (c) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.11.005

文献信息

• 3位双β-咔啉碱类化合物、其制法和其药物组 合物与用途
  申请人：新疆华世丹药物研究有限责任公司

  公开号：CN102952151B

  公开（公告）日：2017-07-28

  本发明公开了3位连接双β‑咔啉碱类化合物、其制法和其药物组合物与用途。具体而言，所述的双β‑咔啉碱类化合物及其可药用盐如通式I所述，这类双β‑咔啉碱类化合物的制备是通过β‑咔啉中间体和二卤代烷烃缩合。本发明还公开了一种药物组合物，包括有效剂量的式I所示双β‑咔啉碱类化合物和药效学上可接受的载体，以及这类双β‑咔啉碱类化合在制备抗肿瘤药物中的应用，包括黑色素瘤、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、结肠癌。
• 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 PREPARATION, PREPARATION PROCESSES AND USE THEREOF
  申请人：Xinjiang Huashidan Pharmaceutical Research Co., Ltd.

  公开号：EP1634881B1

  公开（公告）日：2011-07-27
• US8772311B2
  申请人：——

  公开号：US8772311B2

  公开（公告）日：2014-07-08
• Synthesis and biological evaluation of novel bivalent β-carbolines as potential antitumor agents
  作者：Qifeng Wu、Zhushuang Bai、Qin Ma、Wenxi Fan、Liang Guo、Guoxian Zhang、Liqin Qiu、Huijuan Yu、Guang Shao、Rihui Cao

  DOI：10.1039/c4md00098f

  日期：——

  A series of bivalent β-carbolines with a spacer between the 3-carboxyl oxygens was synthesized and their cytotoxic activities in vitro and antitumor efficacies in vivo were evaluated. Compound 22 exhibited potent antitumor activity against Lewis lung cancer in mice with a tumor inhibition rate of 64.2%.

  一系列具有3-羧基氧之间间隔的双价β-咔啉类化合物被合成，并评估了它们的体外细胞毒活性和体内抗肿瘤效果。化合物22对小鼠Lewis肺癌表现出强效的抗肿瘤活性，肿瘤抑制率为64.2%。