1-(4-Chlorophenyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydro-β-carboline | 82789-40-0

• 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: 1-(4-Chlorophenyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydro-β-carboline
• 英文别名: methyl-1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate；methyl 1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；Methyl 1,2,3,4-tetrahydro-1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carboxylate；1-(4-chlorophenyl)-1,2,3,4-tetrahydro-3-carbomethoxy-β-carboline；methyl 1-(4-chlorophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate
• CAS: 82789-40-0
• 化学式: C₁₉H₁₇ClN₂O₂
• mdl: MFCD00249411
• 分子量: 340.809
• InChiKey: XGVZWMNWLZHJDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-Chlorophenyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydro-β-carboline 在 四丁基溴化铵 、 2-碘酰基苯甲酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 以83%的产率得到methyl 1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  通过Biginelli反应方便地合成1-芳基9 H -β-咔啉-3-甲醛并将其转化为二氢嘧啶酮衍生物

  摘要：

  在目前的工作中，报道了一种实用的1-芳基-β-咔啉-3-甲醛的合成方法，作为通用的结构单元及其在Biginelli反应中的应用。四步合成的起始原料是外消旋色氨酸甲酯。该过程涉及Pictet-Spengler环化，脱氢，酯还原和醇氧化步骤。使用Biginelli反应，将β-咔啉-3-甲醛进一步转化为在位置3上具有药理学意义的二氢嘧啶环的衍生物。

  DOI：

  10.1016/j.tet.2014.06.073
• 作为产物：
  描述：

  L-色氨酸 在 硫酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 1-(4-Chlorophenyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Synthesis, Antileishmanial Activity and Spin Labeling EPR Studies of Novel β-Carboline-Oxazoline and β-Carboline-Dihydrooxazine Derivatives

  摘要：

  A series of novel 1-(substituted-phenyl)-3-(4,5-dihydro-1,3-oxazol-2-yl)-9H-beta-carboline (8a-8i) and 1-(substituted-phenyl)-3-(5,6-dihydro-4H-1,3-oxazin-2-yl)-9H-beta-carboline (9a-9h) derivatives. as well as their respective N-(chloroalkyl)-1-(substituted-phenyl)-9H-beta-carboline-3-carboxamide precursors (6a-6i and 7a-7h), were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. Compounds 8d. 8i, 9e and 9h exhibited significant activity for both promastigote and amastigote forms, with IC50 (50% inhibitory concentration) values ranging from 2.9 to 23.0 mu M. In addition, spin label electron paramagnetic resonance (EPR) spectroscopy studies were carried out for the most active compounds against L amazonensis promastigotes. The studies indicated that the tested compounds cause strong stiffness in the parasite plasma membrane and are capable of inducing internal metalloproteins oxidation of the parasite, resulting in their cross-linking to skeletal proteins. Compounds 8d and 8i produced the largest effect, showing that the presence of oxazoline group at C-3 of beta-carboline nucleus is important for antileishmanial activity.

  DOI：

  10.21577/0103-5053.20200003

文献信息

• Selenium dioxide oxidation of tetrahydro-β-carboline derivatives
  作者：Franco Gatta、Domenico Misiti

  DOI：10.1002/jhet.5570240449

  日期：1987.7

  The oxidation of some tetrahydro-β-carboline derivatives with selenium dioxide led to the formation of 1,4-dihydro or fully aromatic β-carbolines, depending on the nature and the number of substituents at 1 position. The oxidation of 2-acetyl derivatives followed a different course and the products originated by the attack at C-1 of the ring C of the tetrahydro-β-carboline were obtained.

  一些二氢硒化四氢-β-咔啉衍生物的氧化导致形成1,4-二氢或完全芳族的β-咔啉，具体取决于1位取代基的性质和数量。2-乙酰基衍生物的氧化过程不同，得到了由四氢-β-咔啉的C环的C-1攻击所产生的产物。
• [EN] CARBOLINE AND BETACARBOLINE DERIVATIVES FOR USE AS HDAC ENZYME INHIBITORS<br/>[FR] DERIVES DE CARBOLINE ET DE BETACARBOLINE INHIBITEURS DE L'ENZYME HDAC
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2004113336A1

  公开（公告）日：2004-12-29

  Compounds of formula (IA) and (IB) are inhibitors of histone deacetylase activity and useful for the treatment of, inter alia, cancers: wherein fused rings A1 and A2 are optionally substituted; linker radical R1 represents a radical of formula

  式（IA）和（IB）的化合物是组蛋白去乙酰化酶活性的抑制剂，用于治疗癌症等疾病：其中融合的环A1和A2可以选择性地被取代；连接基团R1代表一个公式的基团。
• β-Carboline tethered cinnamoyl 2-aminobenzamides as class I selective HDAC inhibitors: Design, synthesis, biological activities and modelling studies
  作者：Hari Krishna Namballa、Pratibha Anchi、Kesari Lakshmi Manasa、Jay Prakash Soni、Chandraiah Godugu、Nagula Shankaraiah、Ahmed Kamal

  DOI：10.1016/j.bioorg.2021.105461

  日期：2021.12

  revealed the antiproliferative activity of 7h while depolarization of mitochondrial membrane potential by JC-1 was observed in dose-dependent manner. Cell cycle analysis also unveiled the typical accumulation of cells in G2M phase and sub-G1/S phase arrest. In addition, immunoblot analysis for compound 7h on HCT-15 indicated selective inhibition of the protein expression of class I HDAC 2 and 3 isoforms. Molecular

  在本研究中检测了 β-咔啉基序作为含有肉桂酸作为接头和苯甲酰胺作为锌结合基团的 HDAC 抑制剂的作用。已经合成了一系列 β-咔啉-肉桂酰胺偶联物，并评估了它们对不同人类癌细胞系的 HDAC 抑制活性和体外细胞毒性。几乎所有的化合物都表现出比标准药物恩替司他更出色的 HDAC 抑制活性。在测试的化合物中，与标准药物Entinostat (IC 503.87 ± 0.62 µM）。传统的细胞凋亡测定，如核形态改变、AO/EB、DAPI 和 Annexin-V/PI 染色显示7小时的抗增殖活性，而 JC-1 对线粒体膜电位的去极化以剂量依赖性方式观察到。细胞周期分析还揭示了细胞在 G 2 M 期和亚 G 1 /S 期停滞的典型积累。此外，化合物7 h在 HCT-15 上的免疫印迹分析表明选择性抑制 I 类 HDAC 2 和 3 同种型的蛋白质表达。化合物7h的分子对接分析揭示它可以与 HDAC
• Convenient synthesis of 1-aryl-9H-β-carboline-3-carbaldehydes and their transformation into dihydropyrimidinone derivatives by Biginelli reaction
  作者：Péter Ábrányi-Balogh、András Dancsó、Dávid Frigyes、Balázs Volk、György Keglevich、Mátyás Milen

  DOI：10.1016/j.tet.2014.06.073

  日期：2014.9

  In the present work, a practical synthesis of 1-aryl-β-carboline-3-carbaldehydes as versatile building blocks and their application in Biginelli reaction is reported. The starting material of the four-step synthesis is racemic tryptophan methyl ester. The procedure involves a Pictet–Spengler cyclization, a dehydrogenation, an ester reduction, and an alcohol oxidation step. The β-carboline-3-carbaldehydes

  在目前的工作中，报道了一种实用的1-芳基-β-咔啉-3-甲醛的合成方法，作为通用的结构单元及其在Biginelli反应中的应用。四步合成的起始原料是外消旋色氨酸甲酯。该过程涉及Pictet-Spengler环化，脱氢，酯还原和醇氧化步骤。使用Biginelli反应，将β-咔啉-3-甲醛进一步转化为在位置3上具有药理学意义的二氢嘧啶环的衍生物。
• Malaria Box-Inspired Discovery of <i>N</i>-Aminoalkyl-β-carboline-3-carboxamides, a Novel Orally Active Class of Antimalarials
  作者：Jopaul Mathew、Sha Ding、Kevin A. Kunz、Emily E. Stacy、Joshua H. Butler、Reagan S. Haney、Emilio F. Merino、Grant J. Butschek、Zaira Rizopoulos、Maxim Totrov、Maria B. Cassera、Paul R. Carlier

  DOI：10.1021/acsmedchemlett.1c00663

  日期：2022.3.10

  but none potently inhibited growth of the malaria parasite Plasmodium falciparum. Interestingly, 7e, a minor byproduct of these syntheses, proved to be potent in vitro against P. falciparum and was orally efficacious (40 mg/kg) in an in vivo mouse model of malaria.

  使用源自抗疟药 MMV008138 的药效团对公开可用的抗疟药数据库进行虚拟配体筛选，发现 TCMDC-140230（一种四氢-β-咔啉酰胺）值得探索。该结构的所有四种立体异构体均已合成，但没有一种能有效抑制疟疾寄生虫恶性疟原虫的生长。有趣的是，这些合成的次要副产品7e被证明在体外有效对抗恶性疟原虫，并且在疟疾的体内小鼠模型中口服有效 (40 mg/kg) 。