(1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid | 1046143-20-7

• 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: (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
• 英文别名: (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• CAS: 1046143-20-7
• 化学式: C₂₁H₂₂N₂O₅
• 分子量: 382.416
• InChiKey: SAADZRJBOQGELC-MAUKXSAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.8
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid 在 4-二甲氨基吡啶 、 二甲羟胺盐酸盐 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到(15aS,7aS,6R,14R)-6,14-bis(3,4,5-trimethoxyphenyl)-6,8,14,16,14a,15a,6a,7a-octahydro-β-carbolino[2',3'-2,1]piperazino[4,5-b]-β-carboline-7,15-dione
  参考文献：
  名称：

  Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas

  摘要：

  Starting from D-or L-tryptophan, we have synthesized and characterized six compounds 2.29-2.31a and b that belong to a class of nitrogen heterocycles: the carboline-based homodimers. Each individual homodimer features a 1,3-trans relationship on each side of the central diketopiperazine core, but differs in absolute stereochemistry and also in substitution on the 40 and 400 oxygens (-Bn, -CH(3), or -H). The in vitro cytotoxicity of the six compounds was evaluated by measuring the growth inhibition in NCI-H520 and PC-3 human carcinoma cells. Phenol 2.30a inhibited cancer cell growth approximately three times better than its enantiomer 2.30b and possessed a GI(50) comparable to the clinically used agent etoposide in both cell lines. We have concluded that both the stereochemistry imparted by L-tryptophan and the presence of hydroxy substituents at the 40 and 400 positions are necessary to generate cytotoxic properties in the homodimer class. We are now employing 2.30a as a new lead compound in our efforts to discover improved indole-based cancer chemotherapeutics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.022
• 作为产物：
  描述：

  methyl (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到(1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas

  摘要：

  Starting from D-or L-tryptophan, we have synthesized and characterized six compounds 2.29-2.31a and b that belong to a class of nitrogen heterocycles: the carboline-based homodimers. Each individual homodimer features a 1,3-trans relationship on each side of the central diketopiperazine core, but differs in absolute stereochemistry and also in substitution on the 40 and 400 oxygens (-Bn, -CH(3), or -H). The in vitro cytotoxicity of the six compounds was evaluated by measuring the growth inhibition in NCI-H520 and PC-3 human carcinoma cells. Phenol 2.30a inhibited cancer cell growth approximately three times better than its enantiomer 2.30b and possessed a GI(50) comparable to the clinically used agent etoposide in both cell lines. We have concluded that both the stereochemistry imparted by L-tryptophan and the presence of hydroxy substituents at the 40 and 400 positions are necessary to generate cytotoxic properties in the homodimer class. We are now employing 2.30a as a new lead compound in our efforts to discover improved indole-based cancer chemotherapeutics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.022

文献信息

• Discovery of novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents
  作者：Chatchakorn Eurtivong、Lisa I. Pilkington、Michelle van Rensburg、Reuben M. White、Harpreet Kaur Brar、Shaun Rees、Emily K. Paulin、Chris Sun Xu、Nabangshu Sharma、Ivanhoe K.H. Leung、Euphemia Leung、David Barker、Jóhannes Reynisson

  DOI：10.1016/j.ejmech.2019.111919

  日期：2020.2

  Phosphatidylcholine-specific phospholipase C (PC-PLC) is a promising target for new anticancer treatment. Herein, we report our work in the discovery of novel drug-like PC-PLC inhibitors. Virtual screening led to the identification of promising hits from four different structural series that contain the molecular scaffold of benzenesulphonamides (10), pyrido[3,4-b]indoles (22), morpholinobenzoic acid (84) and benzamidobenzoic acid (80). 164 structural analogues were tested to investigate the chemical space around the hit series and to generate preliminary structurally activity relationships (SAR). Two of the pyrido[3,4-b]indoles (22_10 and 22_15) had comparable or better potency as D609, an established but non-drug-like PC-PLC inhibitor. Furthermore, three morpholinobenzoic acids (84, 84_4 and 84_5) had superior potency than D609. Therefore, this study paves the way towards the development of drug-like PL-PLC inhibitors as potential anticancer agents. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas
  作者：Amy M. Deveau、Nancy E. Costa、Elizabeth M. Joshi、Timothy L. Macdonald

  DOI：10.1016/j.bmcl.2008.05.022

  日期：2008.6

  Starting from D-or L-tryptophan, we have synthesized and characterized six compounds 2.29-2.31a and b that belong to a class of nitrogen heterocycles: the carboline-based homodimers. Each individual homodimer features a 1,3-trans relationship on each side of the central diketopiperazine core, but differs in absolute stereochemistry and also in substitution on the 40 and 400 oxygens (-Bn, -CH(3), or -H). The in vitro cytotoxicity of the six compounds was evaluated by measuring the growth inhibition in NCI-H520 and PC-3 human carcinoma cells. Phenol 2.30a inhibited cancer cell growth approximately three times better than its enantiomer 2.30b and possessed a GI(50) comparable to the clinically used agent etoposide in both cell lines. We have concluded that both the stereochemistry imparted by L-tryptophan and the presence of hydroxy substituents at the 40 and 400 positions are necessary to generate cytotoxic properties in the homodimer class. We are now employing 2.30a as a new lead compound in our efforts to discover improved indole-based cancer chemotherapeutics. (C) 2008 Elsevier Ltd. All rights reserved.