(1R,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid | 246137-74-6

• 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,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid
• 英文别名: (1R,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid；1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid；(1R,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• CAS: 246137-74-6
• 化学式: C₁₈H₁₆N₂O₂
• 分子量: 292.337
• InChiKey: ZJSUEWDIHUPPRO-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid 在 sodium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 82.0h， 生成 trans-2-<2-(4-phenylpiperazin-1-yl)ethyl>-5-phenyl-5,6,11,11a-tetrahydro-1H-imidazo<1',5':1,6>pyrido<3,4-b>indole-1,3(2H)-dione
  参考文献：
  名称：

  α1-肾上腺素能受体试剂。合成一些5,6,11,11a-四氢-1H-咪唑并[1'，5'：1,6]吡啶和5,6,11,11b-四氢-1H-咪唑并[1'，5'：1 ，2] pyrido [3,4-b] indole-1,3（2H）-diones。

  摘要：

  几个2-取代的5,6,11,11a-四氢-1H-咪唑[1'，5'：1,6]吡啶（1）和5,6,11,11b-四氢-1H-咪唑[1'，合成并合成了5'：1,2]吡啶基[3,4-b]吲哚，3（2H）-二酮（2），并通过2D-NMR光谱和核相差Overhauser效应实验研究。通过放射性配体受体结合试验评估了所有化合物的体外α（1）肾上腺素受体亲和力。从大鼠皮膜置换[3H]吡唑嗪最活跃的衍生物是1b（K（i）= 219 nM）。在1 microM浓度下，化合物1和2对苯二氮卓或5-HT（1A）受体没有影响。1b的生物学活性使它可能成为设计新的选择性α1肾上腺素受体配体的先导化合物。

  DOI：

  10.1248/cpb.43.941
• 作为产物：
  描述：

  苯甲醛 、 D-色氨酸 在 硫酸 作用下， 以66%的产率得到(1R,3R)-1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5

  摘要：

  The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.027

文献信息

• Microwave accelerated Pictet–Spengler reactions of tryptophan with ketones directed toward the preparation of 1,1-disubstituted indole alkaloids
  作者：Fu-Ming Kuo、Ming-Chung Tseng、Ya-Hew Yen、Yen-Ho Chu

  DOI：10.1016/j.tet.2004.10.025

  日期：2004.12

  Using the Pictet–Spengler reactions of tryptophan with aldehydes under acidic conditions at ambient temperature, diastereoisomers of 1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines could readily be furnished in short time (0.5–4 h) with good to excellent yields (50–98%). Though intrinsically slow in reaction rates, ketone reactions can be accelerated (from days to minutes) using microwaves in open

  使用色氨酸与醛在环境温度下的酸性条件下的Pictet-Spengler反应，可以轻松地在短时间内（0.5–4小时）提供1,3-二取代-1,2,3,4-四氢-β-咔啉的非对映异构体），具有良好至极佳的收率（50–98％）。尽管反应速度本质上很慢，但在开放的容器中使用微波可以加速酮的反应（从几天到几分钟），分离产率高（67-99％），这使这些咔啉成为合成天然和非天然吲哚生物碱的可行反应中间体。 。简要讨论了两种吲哚生物碱的制备，即四氢-β-咔啉二酮哌嗪和四氢-β-咔啉乙内酰脲。
• 芳基取代的1H-吡啶[3,4-b]吲哚-3-羧酸甲酯 的手性拆分
  申请人：西华大学

  公开号：CN108409731B

  公开（公告）日：2020-11-20

  本发明公开了一种以S‑1‑(2‑叔丁基苯基)乙胺为手性拆分试剂，对一类含两个手性中心的1‑芳基‑1H‑吡啶[3,4‑b]吲哚‑3‑羧酸甲酯非对应异构体进行手性拆分的方法。该方法主要经过水解、拆分、解离、酯化等主要实验步骤。该方法具有拆分收率高、手性拆分试剂容易获得、手性拆分试剂易回收、拆分效果良好等特点。
• 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.
• Application of chlorotrimethylsilane in Pictet–Spengler reaction
  作者：Sergey V. Ryabukhin、Dmitriy M. Panov、Andrey S. Plaskon、Andrey A. Tolmachev、Radomyr V. Smaliy

  DOI：10.1007/s00706-012-0804-7

  日期：2012.11

  Chlorotrimethylsilane has been found to be an efficient condensing agent in the Pictet-Spengler reaction, affording an extremely straightforward synthetic route to tetrahydro-beta-carboline derivatives and their analogs. The applicability of the method has been studied, and a representative library of structurally diverse products has been created..
• Synthesis and biological evaluation of new tetrahydro-β-carbolines as inhibitors of the mitotic kinesin Eg5
  作者：Nils Sunder-Plassmann、Vasiliki Sarli、Michael Gartner、Mathias Utz、Jeanette Seiler、Stefan Huemmer、Thomas U. Mayer、Thomas Surrey、Athanassios Giannis

  DOI：10.1016/j.bmc.2005.06.027

  日期：2005.11

  The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor. (c) 2005 Elsevier Ltd. All rights reserved.