methyl-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate | 82789-21-7

• 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: methyl-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
• 英文别名: methyl 1-(4-nitrophenyl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylate；1-(4-nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester；1-(4-Nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carbolin-3-carbonsaeure-methylester；methyl 1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate；methyl 1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 82789-21-7
• 化学式: C₁₉H₁₇N₃O₄
• mdl: MFCD00264010
• 分子量: 351.362
• InChiKey: PMTFLAWFQMHLPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 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：
  99.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 在 盐酸 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 乙醇 、 四丁基溴化铵 、 calcium chloride 、 2-碘酰基苯甲酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 5-acetyl-6-methyl-4-[1-(4-nitrophenyl)-9H-β-carbolin-3-yl]-3,4-dihydropyrimidin-2(1H)-one
  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 methyl-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate
  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

• β-Carboline and N-hydroxycinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma
  作者：Yong Ling、Wei-Jie Gao、Changchun Ling、Ji Liu、Chi Meng、Jianqiang Qian、Siqun Liu、Huiling Gan、Hongmei Wu、Jinhua Tao、Hong Dai、Yanan Zhang

  DOI：10.1016/j.ejmech.2019.02.054

  日期：2019.4

  developed a series of novel hybrids of β-carboline and N-hydroxycinnamamide as histone deacetylase (HDAC) inhibitors. Most of the hybrids 13a-p showed strong antiproliferative effects with low-micromolar IC50 values against four human cancer cells. The most potent compound of series 13p exhibited high HDAC1/6 inhibitory effects, and also increased the acetylation levels of histone H3, H4 and α-tubulin

  为了努力开发可以克服耐药性（导致癌症死亡的首要原因）的抗癌剂，我们开发了一系列新型的β-咔啉和N-羟基肉桂酰胺作为组蛋白脱乙酰基酶（HDAC）抑制剂。大多数杂种13a-p对四种人类癌细胞均表现出很强的抗增殖作用，且低微摩尔IC 50值。13p系列最有效的化合物显示出高HDAC1 / 6抑制作用，并且还提高了组蛋白H3，H4和α-微管蛋白的乙酰化水平。重要的是，13p对药物敏感的HepG2和Bel7402细胞以及耐药的Bel7402 / 5FU细胞表现出很高的抗癌能力。混合13p通过调节这些Bel7402 / 5FU细胞中凋亡相关蛋白的表达，触发了明显的凋亡。最后，13p通过在Bel7402 / 5FU细胞中增加LC3-II的表达以及p62和LC3-I的表达的退化而诱导了大量的自噬通量活性。总体而言，13p是一种新型的β-咔啉/ N-羟基肉桂酰胺杂化物，具有显着的抗癌效力，值得进一步评估其对耐药性肝细胞癌的治疗。
• Dehydrogenation of 1-aryl(hetaryl)-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acids and their esters with dimethyl sulfoxide
  作者：M. G. Abramyants、D. A. Lomov、T. I. Zavyazkina

  DOI：10.1134/s1070428016110117

  日期：2016.11

  boline-3-carboxylic acids derivatives with dimethyl sulfoxide leads to the formation of 1-aryl(hetaryl)-9Н-β-carbolines. Simultaneously with the dehydrogenation decarboxylation occurs. At the oxidation with dimethyl sulfoxide of methyl 1-aryl (hetaryl)-1,2,3,4-tetrahydro-9Н-β-carboline-3-carboxylicates methyl 1-aryl(hetaryl)-9Н-β-carboline-3-carboxylates formed whose hydrolysis afforded the corresponding

  1-芳基（杂芳基）-1,2,3,4-四氢-9-氧化脱氢Н -β-β-咔啉-3-羧酸的衍生物与二甲亚砜通向1-芳基（杂芳基）-9形成Н - β-咔啉。与脱氢同时发生脱羧。在用甲基1-芳的二甲亚砜（杂芳基）-1,2,3,4-四氢-9-氧化Н -β-β-咔啉-3- carboxylicates甲基-1-芳基（杂芳基）-9- Н -β咔啉形成3-羧酸盐，其水解得到相应的1-芳基（杂芳基）-9Н -β-咔啉-3-羧酸。
• Highly efficient Lewis acid-catalysed Pictet–Spengler reactions discovered by parallel screeningElectronic supplementary information (ESI) available: full experimental procedures. See http://www.rsc.org/suppdata/cc/b2/b212063a/
  作者：Natarajan Srinivasan、A. Ganesan

  DOI：10.1039/b212063a

  日期：2003.3.24

  High yielding Lewis acid-catalysed one-pot Pictet–Spengler reactions of tryptophan methyl ester and tryptamine with aliphatic and aromatic aldehydes were achieved in short reaction times with the aid of microwave irradiation.

  高产量的路易斯酸催化的一锅法Pictet–Spengler反应，采用色氨酸甲酯和色氨酸与脂肪族和芳香族醛在微波辐射的帮助下，在短反应时间内完成。
• Oncogenic-RAS-signal dependent lethal compounds
  申请人：Stockwell Brent R.

  公开号：US20100081654A1

  公开（公告）日：2010-04-01

  Compounds with cancer cell specific lethality are provided. In particular, RAS-selective lethal compounds and compositions are provided. Also provided are methods of screening for such compounds and methods of treating a condition in a mammal, by administering to the mammal a therapeutically effective amount of such compounds or compositions.

  提供了具有癌细胞特异性致死性的化合物。特别地，提供了选择性致死RAS化合物和组合物。还提供了筛选此类化合物的方法以及通过向哺乳动物投与此类化合物或组合物的治疗有效量来治疗哺乳动物病症的方法。
• Room-Temperature Aromatization of Tetrahydro-β-carbolines by 2-Iodoxybenzoic Acid: Utility in a Total Synthesis of Eudistomin U
  作者：Joseph D. Panarese、Stephen P. Waters

  DOI：10.1021/ol101688x

  日期：2010.9.17

  2-Iodoxybenzoic acid is a convenient reagent for the dehydrogenation of tetrahydro-beta-carbolines to their aromatic forms under mild conditions. The utility of the method was demonstrated in a total synthesis of the marine indole alkaloid eudistomin U.