methyl (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate | 274677-71-3

• 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: methyl (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 274677-71-3
• 化学式: C₂₂H₂₄N₂O₅
• 分子量: 396.443
• InChiKey: COBLTLPBNAVOBY-QFBILLFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 哌啶 、 sodium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 生成 (2R,8S)-2-(3,4,5-trimethoxyphenyl)-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
  参考文献：
  名称：

  Synthesis and Evaluation of Tryprostatin B and Demethoxyfumitremorgin C Analogues

  摘要：

  Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G(2)/M transition. N-Alkyl derivatives of the L-TrP-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these were more active than the natural product. A second series of cis- and trans-tetrahydro-beta-carbolines annulated to a diketopiperazine were prepared as analogues of demethoxyfumitremorgin C. The nature of the alkyl substituent, as well as its cis or trans relationship in the tetrahydro-beta-carboline ring, was found to have a significant effect on cytotoxic activity. Small cis-alkyl substituents fall into the demethoxyfumitremorgin C family, whereas bulky benzyl trans compounds appear to act via a different mechanism of action.

  DOI：

  10.1021/jm9905662
• 作为产物：
  描述：

  L-色氨酸甲酯 在 三氟乙酸 、 原甲酸三甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 26.5h， 生成 methyl (1R,3S)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Synthesis and Evaluation of Tryprostatin B and Demethoxyfumitremorgin C Analogues

  摘要：

  Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G(2)/M transition. N-Alkyl derivatives of the L-TrP-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these were more active than the natural product. A second series of cis- and trans-tetrahydro-beta-carbolines annulated to a diketopiperazine were prepared as analogues of demethoxyfumitremorgin C. The nature of the alkyl substituent, as well as its cis or trans relationship in the tetrahydro-beta-carboline ring, was found to have a significant effect on cytotoxic activity. Small cis-alkyl substituents fall into the demethoxyfumitremorgin C family, whereas bulky benzyl trans compounds appear to act via a different mechanism of action.

  DOI：

  10.1021/jm9905662

文献信息

• Synthesis of 2-[3-(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-1H-β-carbolines as a new class of antimalarial agents
  作者：Leena Gupta、Kumkum Srivastava、Shubhra Singh、S.K. Puri、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2008.04.030

  日期：2008.6

  A series of hybrid molecules 2-[3-(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-1H-beta-carbolines have been synthesized and screened for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum. Compounds 26, 32, and 34 have shown MIC in the range of 0.05-0.11 microM and are in vitro several folds more active than chloroquine

  合成了一系列杂化分子2- [3-（7-氯喹啉-4-基氨基）-烷基] -1-（取代的苯基）-2,3,4,9-四氢-1H-β-咔啉并筛选了它们对恶性疟原虫氯喹敏感菌株的体外抗疟活性。化合物26、32和34的MIC在0.05-0.11 microM的范围内，并且在体外具有比氯喹高几倍的活性。
• Design and Synthesis of C3-Pyrazole/Chalcone-Linked Beta-Carboline Hybrids: Antitopoisomerase I, DNA-Interactive, and Apoptosis-Inducing Anticancer Agents
  作者：Ahmed Kamal、Vunnam Srinivasulu、V. Lakshma Nayak、Manda Sathish、Nagula Shankaraiah、Chandrakant Bagul、N. V. Subba Reddy、Nandini Rangaraj、Narayana Nagesh

  DOI：10.1002/cmdc.201300406

  日期：2014.9

  substitutions at positions 1 and 3 of these hybrids was clearly addressed. Further, induction of apoptosis was confirmed by Annexin V‐FITC, Hoechst staining, and DNA fragmentation analysis. In addition, DNA photocleavage studies proved that two of the hybrids, (E)‐1‐(furan‐2‐yl)‐3‐(1‐(4‐(trifluoromethyl)phenyl)‐9H‐pyrido[3,4‐b]indol‐3‐yl)prop‐2‐en‐1‐one (7 d) and 1‐(3‐(furan‐2‐yl)‐5‐(1‐(4‐(trifluoromethyl)phenyl)‐9H‐pyrido[3

  设计，合成并评估了一系列分别在C1和C3位置带有取代苯基和查耳酮/（N-乙酰基）-吡唑部分的β-咔啉杂化物。这些新的杂合分子表现出显著的细胞毒活性，用IC 50个值范围为<2.0μ中号至80μ中号，并与取代位置1和这些杂种显然解决的3相关联的结构-活性关系（SAR）。此外，膜联蛋白V-FITC，Hoechst染色和DNA片段分析证实了凋亡的诱导。此外，DNA光裂解研究证明其中两个杂种（E）-1（呋喃-2-基）-3-（1-（4-（三氟甲基）苯基）-9 H-pyrido [3,4- b ]吲哚-3-基）prop-2-en-1-one（7 d）和1-（3-（呋喃-2-基）-5-（1-（4- （三氟甲基）苯基）-9 H-吡啶基[3,4- b ]吲哚-3-基）-4,5-二氢-1 H-吡唑-1-基）乙酮（8 d）可以有效切割pBR322质粒DNA在用紫外线照射时。主动混合动力8 d抑制DNA拓扑异构酶
• DNA-binding affinity and anticancer activity of β-carboline–chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis
  作者：Nagula Shankaraiah、K.P. Siraj、Shalini Nekkanti、Vunnam Srinivasulu、Pankaj Sharma、Kishna Ram Senwar、Manda Sathish、M.V.P.S. Vishnuvardhan、Sistla Ramakrishna、Chetna Jadala、Narayana Nagesh、Ahmed Kamal

  DOI：10.1016/j.bioorg.2015.02.007

  日期：2015.4

  A new series of DNA-interactive beta-carboline-chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 ( lung adenocarcinoma) cell lines with IC50 values lower than 10 mu M. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 mu M. In addition, compounds 7e, 7k, 7p-u has displayed significant elevation in Delta T-m of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies. (C) 2015 Elsevier Inc. All rights reserved.
• Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents
  作者：Ravi Kumar、Leena Gupta、Pooja Pal、Shahnawaz Khan、Neetu Singh、Sanjay Babu Katiyar、Sanjeev Meena、Jayanta Sarkar、Sudhir Sinha、Jitendra Kumar Kanaujiya、Savita Lochab、Arun Kumar Trivedi、Prem M.S. Chauhan

  DOI：10.1016/j.ejmech.2010.02.001

  日期：2010.6

  A series of tetrahydro-beta-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC(50) values of 1058, 664 7 and 122.2 nM, respectively, while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2 5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC(50) value of 740 nM, also arrests cell cycle in G(1) phase and induces apoptosis in MCF7 and MDA MB231cell lines.
• 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.