9-methyl-1-phenyl-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-methyl-1-phenyl-β-carboline-3-carboxylic acid
• 英文别名: 9-Methyl-1-phenylpyrido[3,4-b]indole-3-carboxylic acid
• 化学式: C₁₉H₁₄N₂O₂
• 分子量: 302.332
• InChiKey: GQFOWTCRPVXTJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 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-methyl-1-phenyl-β-carboline-3-carboxylic acid 、 1-苄基哌嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 以78%的产率得到(4-benzylpiperazin-1-yl)(9-methyl-1-phenyl-9H-pyrido[3,4-b]indol-3-yl)methanone
  参考文献：
  名称：

  9-甲基-1-苯基-9H-吡啶并[3,4-b]吲哚衍生物作为抗利什曼制剂的生物学评价和结构活性关系。

  摘要：

  通过分子杂交方法设计了一系列哌嗪基-β-咔啉-3-羧酰胺衍生物。合成，表征了设计的类似物，并评估了其对婴儿利什曼原虫和多形利什曼原虫的抗利什曼原虫活性。在婴儿乳杆菌的抑制测定中，化合物7d，7g和7c对前鞭毛体（分别为EC50 1.59、1.47和3.73 µM）和变形虫（EC50分别为1.4、1.9和2.6 µM）显示出有效的抑制作用。SAR研究表明，邻位甲氧基，氯基和甲基的对位取代有利于抗婴儿利什曼原虫的活性。在这些类似物7d，7h，7n和7g中，它们显示出对多诺氏乳杆菌前鞭毛体（分别为EC50 0.91、4.0、4.57和5.02μM），轴突性吻合动物（EC50为0.9、3.5、2.2和3）的有效抑制作用。分别为8 µM）和胞内变形虫（EC50分别为1.3、7.8、5.6和6.3 µM）。SAR研究表明，甲氧基的对位取代，氯基的对位和间位取代以及苄基取代被推荐用于对多诺氏乳杆菌有显着的抗利什曼肽作用。

  DOI：

  10.1016/j.bioorg.2018.11.037
• 作为产物：
  描述：

  DL-色氨酸 在 potassium permanganate 、 氯化亚砜 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 二甲基亚砜 为溶剂， 反应 28.5h， 生成 9-methyl-1-phenyl-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  9-甲基-1-苯基-9H-吡啶并[3,4-b]吲哚衍生物作为抗利什曼制剂的生物学评价和结构活性关系。

  摘要：

  通过分子杂交方法设计了一系列哌嗪基-β-咔啉-3-羧酰胺衍生物。合成，表征了设计的类似物，并评估了其对婴儿利什曼原虫和多形利什曼原虫的抗利什曼原虫活性。在婴儿乳杆菌的抑制测定中，化合物7d，7g和7c对前鞭毛体（分别为EC50 1.59、1.47和3.73 µM）和变形虫（EC50分别为1.4、1.9和2.6 µM）显示出有效的抑制作用。SAR研究表明，邻位甲氧基，氯基和甲基的对位取代有利于抗婴儿利什曼原虫的活性。在这些类似物7d，7h，7n和7g中，它们显示出对多诺氏乳杆菌前鞭毛体（分别为EC50 0.91、4.0、4.57和5.02μM），轴突性吻合动物（EC50为0.9、3.5、2.2和3）的有效抑制作用。分别为8 µM）和胞内变形虫（EC50分别为1.3、7.8、5.6和6.3 µM）。SAR研究表明，甲氧基的对位取代，氯基的对位和间位取代以及苄基取代被推荐用于对多诺氏乳杆菌有显着的抗利什曼肽作用。

  DOI：

  10.1016/j.bioorg.2018.11.037

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
• Design, synthesis of new β-carboline derivatives and their selective anti-HIV-2 activity
  作者：Penta Ashok、Subhash Chander、Jan Balzarini、Christophe Pannecouque、Sankaranarayanan Murugesan

  DOI：10.1016/j.bmcl.2015.01.058

  日期：2015.3

  In the present study, a new series of beta-carboline derivatives were synthesized and evaluated for inhibition activity against both HIV-1 and HIV-2 strains. Among these reported analogues, surprisingly (1-phenyl-9H-pyrido[3,4-b] indol-3-yl)(4-p-tolylpiperazin-1-yl) methanone (7b), (4-(2-methoxyphenyl) piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b] indol-3-yl) methanone (7f), (4-(4-fluorophenyl) piperazin-1-yl) (1-phenyl-9H-pyrido[3,4-b] indol-3-yl) methanone (7k), (4-(2-fluorophenyl) piperazin-1-yl)(1-phenyl-9H-pyrido[3,4-b] indol-3-yl) methanone (7l) displayed selective inhibition of HIV-2 strain with EC50 values of 3.3, 3.2, 2.6 and 5.4 mu M, respectively, which are comparable with nucleoside reverse transcriptase inhibitors lamivudine and dideoxyinosine. As these analogues have not shown in vitro HIV-2 reverse transcriptase inhibition, it could be excluded as potential target for their specific anti-HIV-2 activity. (C) 2015 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of diarylpiperazine derivatives as potent anti-tubercular agents
  作者：Ashok Penta、Scott Franzblau、Baojie Wan、Sankaranarayanan Murugesan

  DOI：10.1016/j.ejmech.2015.10.024

  日期：2015.11

  Molecular hybridization is an emerging approach to design novel ligands by combination of two or more pharmacophoric subunits of known bioactive compounds. In the present study, we have designed a novel series of diarylpiperazine analogues, synthesized, characterized using FTIR, H-1 NMR, Mass, Elemental analysis and evaluated their in-vitro anti-tubercular activity. Among the reported sixteen diarylpiperazines, eleven analogues exhibited significant anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC values below 6.25 mu g/mL and good selectivity index. Structure activity relationship studies concluded that, ortho-para directing group (except para chloro) substitution on ortho and para position of piperazine attached phenyl ring favored anti-tubercular activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
• 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.