(S)-1-p-Tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester | 865619-27-8

• 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: (S)-1-p-Tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
• CAS: 865619-27-8
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: BEEVAEJHPKFYMA-ZENAZSQFSA-N

物化性质

• 沸点：
  502.5±50.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.12
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-1-p-Tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  A β-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer

  摘要：

  DOI：

  10.1021/acs.jmedchem.4c00030
• 作为产物：
  描述：

  L-色氨酸 在 氯化亚砜 、 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 (S)-1-p-Tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  鬼臼毒素连接的β-咔啉同类物的合成作为潜在的抗癌药和DNA拓扑异构酶II抑制剂

  摘要：

  通过将各种取代的β-咔啉酸与4β-氨基鬼臼毒素耦合，合成了一系列新的鬼臼毒素连接的β-咔啉同类物。评估它们对一组人类癌细胞系（例如肺癌（A549），前列腺癌（DU-145），MDA MB-231（乳腺癌），HT-29（结肠癌）和HeLa（子宫颈癌））的抗癌活性）表明7i和7j是最具细胞毒性的化合物，对DU-145细胞系的IC 50值分别为1.07±0.07μM和1.14±0.16。此外，详细的生物学研究（例如细胞周期分析，拓扑异构酶II抑制，彗星分析，DNA结合研究和对接研究）表明，这些同类物是DNA相互作用的拓扑异构酶II抑制剂。

  DOI：

  10.1016/j.ejmech.2017.12.055

文献信息

• PhI(OAc)₂-mediated one-pot oxidative decarboxylation and aromatization of tetrahydro-β-carbolines: synthesis of norharmane, harmane, eudistomin U and eudistomin I
  作者：Ahmed Kamal、Yellaiah Tangella、Kesari Lakshmi Manasa、Manda Sathish、Vunnam Srinivasulu、Jadala Chetna、Abdullah Alarifi

  DOI：10.1039/c5ob00871a

  日期：——

  A new strategy for synthesis of β-carbolines via one-pot oxidative decarboxylation at room temperature is developed for the first time.

  首次开发了一种在室温下通过一锅法氧化脱羧合成β-咔啉的新策略。

• Design and synthesis of thiadiazolo-carboxamide bridged β-carboline-indole hybrids: DNA intercalative topo-IIα inhibition with promising antiproliferative activity
  作者：Ramya Tokala、Sravani Sana、Uppu Jaya Lakshmi、Prasanthi Sankarana、Dilep Kumar Sigalapalli、Nikhil Gadewal、Jyoti Kode、Nagula Shankaraiah

  DOI：10.1016/j.bioorg.2020.104357

  日期：2020.12

  impressive cytotoxicity against A549 cell line (IC50: 3.00 ± 1.40 μM). Further target-based assay of these two compounds 12c and 12a revealed their potential as DNA intercalative topoisomerase-IIα inhibitors. Additionally, the antiproliferative activity of compound 12c was measured in A549 cells by traditional apoptosis assays revealing the nuclear, morphological alterations, and depolarization of membrane

  通过构建噻二唑-甲酰胺桥接的 β-咔啉-吲哚杂化物来结合显着的药效团特性，从而指导主要细胞毒剂的开发。在体外细胞毒性潜力的评估中， 12c在合成的新分子12a – k中表现出惊人的细胞毒性， 在所有测试的癌细胞系（A549、MDA-MB-231、BT-474、HCT）中，IC 50 < 5 μM -116, THP-1)，在肺癌细胞系 (A549) 中表达最佳细胞毒潜力，IC 50值为 2.82 ± 0.10 μM。此外，另一种化合物12a对 A549 细胞系也显示出令人印象深刻的细胞毒性 (IC 50: 3.00 ± 1.40 μM)。这两种化合物12c和12a的进一步基于靶点的测定揭示了它们作为 DNA 嵌入拓扑异构酶-IIα 抑制剂的潜力。此外，通过传统的细胞凋亡测定法在 A549 细胞中测量了化合物12c的抗增殖活性，揭示了线粒体中细胞核、形态学改变和膜电位的去极化以及磷脂酰丝氨酸
• Design, synthesis and biological evaluation of new β-carboline-bisindole compounds as DNA binding, photocleavage agents and topoisomerase I inhibitors
  作者：Jeshma Kovvuri、Burri Nagaraju、V. Lakshma Nayak、Ravikumar Akunuri、M.P. Narasimha Rao、Ayyappan Ajitha、Narayan Nagesh、Ahmed Kamal

  DOI：10.1016/j.ejmech.2017.10.054

  日期：2018.1

  antiproliferative activity against DU-145 cells with IC50 values 1.86 and 1.80 μM respectively. Further, these compounds effectively inhibit DNA topoisomerase I activity and can also cleave the pBR322 plasmid upon irradiation with UV light. In addition, Annexin V-FITC assay suggested that these compounds induced apoptosis in DU- 145 cell line (prostate cancer). To know the binding mode of these compounds with DNA

  设计，合成和评估了一系列新的β-咔啉-双吲哚化合物对人类癌细胞系（例如A549（肺癌），DU-145（前列腺癌），HeLa（宫颈癌）和MCF- 7（乳腺癌）。所有化合物均显示出相当大的抗增殖活性。其中，化合物7g和7r对具有IC 50的DU-145细胞表现出显着的抗增殖活性值分别为1.86和1.80μM。此外，这些化合物有效抑制DNA拓扑异构酶I活性，并且还可以在用紫外线照射时切割pBR322质粒。另外，膜联蛋白V-FITC测定表明这些化合物诱导DU-145细胞系（前列腺癌）中的细胞凋亡。为了了解这些化合物与DNA的结合方式，还进行了光谱研究。这些新化合物显示出与DNA结合的独特模式，无论是生物物理研究，例如紫外可见，荧光，圆二色性和分子对接研究，都表明β-咔啉-双吲哚化合物表现出与DNA相互作用的梳理类型。
• Synthesis of fused tetrahydro-β-carbolinequinoxalinones in 1-n-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide ([bdmim][Tf2N]) and 1-n-butyl-2,3-dimethylimidazolium perfluorobutylsulfonate ([bdmim][PFBuSO3]) ionic liquids
  作者：Ming-Chung Tseng、Yang-Min Liang、Yen-Ho Chu

  DOI：10.1016/j.tetlet.2005.06.153

  日期：2005.9

  Starting from tryptophan methyl ester, a three-step synthesis of fused tetrahydro-beta-carbolinequinoxalinones in two new ionic liquids, [bdmim][Tf2N] and [bdmim][PFBUSO3], was described. Both ionic liquids can be readily prepared from commercially available starting materials in high yields. Unlike the commonly used [PF6]-based ionic liquids that evidently undergo slow hydrolysis of the PF6 anion with the concomitant release of HF, ionic liquids of [bdmim][Tf2N] and [bdmim][PFBuSO3] are not only chemically stable but also apparently inert to hydrolysis and therefore organic reactions carried out in both ionic liquids proceed smoothly with good yields. The overall isolated yields for this three-step synthesis of tetrahydro-beta-carbolinequinoxalinones were 34-55%. To the best of our knowledge, the preparation of fused tetrahydro-beta-carbolinequinoxalinones was unprecedented. (c) 2005 Elsevier Ltd. All rights reserved.
• Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells
  作者：Yong Ling、Jing Guo、Qiuxing Yang、Peng Zhu、Jiefei Miao、Weijie Gao、Yanfu Peng、Jiaying Yang、Kun Xu、Biao Xiong、Gongqing Liu、Jinhua Tao、Lin Luo、Qing Zhu、Yanan Zhang

  DOI：10.1016/j.ejmech.2017.12.061

  日期：2018.1

  A series of novel beta-carboline-based hydroxamate derivatives 12a-k were designed and synthesized, and their biological activities in a series of in vitro assays were evaluated. Several of these beta-carboline derivatives not only showed excellent HDAC1/3/6 inhibitory effects, but also displayed significant antitumor activities against five human cancer cells. The most potent compound 12f demonstrated the highest anticancer potency against cancer cell lines with IC50 values of 0.53-1.56 mu M, which was considerably more potent than harmine (IC50 = 46.7-55.3 mu M) and also three-to ten-fold lower than that of SAHA (IC50=4.48-6.26 mu M). Immunoblot analysis revealed that 12f dose-dependently inhibited histone H3 and a-tubulin acetylation, confirming its HDAC inhibitory effects. Moreover, 12f significantly arrested HepG2 cells at G2/M phase through inhibiting cell cycle related protein CDK1 and cyclin B in a concentration dependent manner. Interestingly, 12f also exerted strong anti-metastasis activity by simultaneously reducing the protein level of MMP2 and MMP9 and inhibiting MAPK signaling pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.