9-(3-phenyl)propyl-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-(3-phenyl)propyl-1-methyl-β-carboline-3-carboxylic acid
• 英文别名: 9-(3-phenylpropyl)-1-methyl-β-carboline-3-carboxylic acid；9-phenylpropyl-1-methyl-β-carboline-3-carboxylic acid；1-Methyl-9-(3-phenylpropyl)pyrido[3,4-b]indole-3-carboxylic acid
• 化学式: C₂₂H₂₀N₂O₂
• 分子量: 344.413
• InChiKey: AUFLKJQUMNBNFJ-UHFFFAOYSA-N

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：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-(3-phenyl)propyl-1-methyl-β-carboline-3-carboxylic acid 、 1,9-二溴壬烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以49%的产率得到1,9-bis[9-(3-phenylpropyl)-1-methyl-β-carboline-3-carboxylic acid] nonanediyl 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-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid 在 sodium hydroxide 、 氯化亚砜 、 sodium hydride 、 sulfur 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 13.0h， 生成 9-(3-phenyl)propyl-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

• 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%。
• Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives
  作者：Rihui Cao、Wenlie Peng、Hongsheng Chen、Xuerui Hou、Huaji Guan、Qi Chen、Yan Ma、Anlong Xu

  DOI：10.1016/j.ejmech.2004.11.005

  日期：2005.3

  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.