methyl (3S)-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate | 1085709-15-4

• 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 (3S)-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1085709-15-4
• 化学式: C₁₉H₁₇N₃O₄
• 分子量: 351.362
• InChiKey: PMTFLAWFQMHLPS-BHWOMJMDSA-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 (3S)-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 potassium permanganate 、 一水合肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(4-nitrophenyl)-β-carboline-3-carboxylic acid hydrazide
  参考文献：
  名称：

  Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with antiproliferative and antimetastatic activities in human cancer cells

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2017.12.061
• 作为产物：
  描述：

  L-色氨酸 在 氯化亚砜 、 溶剂黄146 作用下， 反应 4.33h， 生成 methyl (3S)-1-(4-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Synthesis and Fungicidal Activity of β-Carboline Alkaloids and Their Derivatives

  摘要：

  本研究设计、合成并评估了一系列β-吲哚衍生物的杀菌活性。几个衍生物表现出对某些真菌的选择性杀菌活性。特别是，化合物F5对根腐病菌（Rhizoctonia solani）的杀菌活性（53.35%）高于商业抗病毒药物惟克（validamycin）的活性（36.4%）；化合物F16对柑橘糠病菌（Oospora citriaurantii ex Persoon）的杀菌活性较高（43.28%）。一些生物碱及其衍生物（化合物F4和F25）表现出广谱的杀菌活性。具体来说，化合物F4在体外表现出优异的广谱杀菌活性，对荔枝病（P. litchi）的治愈和保护活性分别达到92.59%和59.26%。新衍生物F4具有优化的物理化学性质，明显在体内外展现出更高的活性；因此，F4可能作为新型杀菌药物研发的领先结构。

  DOI：

  10.3390/molecules200813941

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。

• Iodine-catalyzed one-pot decarboxylative aromatization of tetrahydro-β-carbolines
  作者：Ramu Meesala、Ahmad Saifuddin Mohamad Arshad、Mohd Nizam Mordi、Sharif Mahsufi Mansor

  DOI：10.1016/j.tet.2016.10.069

  日期：2016.12

  A synthetic strategy was developed for the preparation of β-carbolines by one-pot decarboxylation and aromatization of tetrahydro-β-carboline-3-carboxylic acids by employing 10 mol% of iodine in presence of oxidant aqueous H2O2. The method was also successfully extended for the aromatization of tetrahydro-β-carboline-3-methyl esters. The utility of the method was demonstrated in the synthesis of β-carboline

  合成策略用于制备β咔啉通过一锅脱羧和四氢β咔啉-3-羧酸的芳构化通过采用10mol％的碘在氧化剂水溶液H的存在开发2 Ò 2。该方法也成功地扩展到四氢-β-咔啉-3-甲基酯的芳构化。该方法的实用性在β-咔啉生物碱正丹烷，丹参烷和芥子气素N的合成中得到了证明。
• Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1)
  作者：Anelise S. Nazari Formagio、Patricia R. Santos、Karine Zanoli、Tania Ueda-Nakamura、Lilian T. Düsman Tonin、Celso V. Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2009.07.005

  日期：2009.11

  Several novel 1,3-disubstituted β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were synthesized and evaluated for their antiviral activity against vaccinal poliovirus (VP) and herpes simplex virus type 1 (HSV-1). The cytotoxicity and selectivity index of the active compounds were also evaluated. Among the synthesized derivatives, compounds 10 and 11 displayed potent activity

  合成了几种新颖的在C-3带有一个取代的碳酰肼基团的1,3-二取代的β-咔啉衍生物，并评估了它们对疫苗脊髓灰质炎病毒（VP）和1型单纯疱疹病毒（HSV-1）的抗病毒活性。还评估了活性化合物的细胞毒性和选择性指数。在合成的衍生物中，化合物10和11对疫苗的脊髓灰质炎病毒和HSV-1病毒均显示出有效的活性。化合物10表现出对HSV-1病毒的最高选择性指数（SI = 2446.8）和低细胞毒性（CC 50  = 1150.0±67.3μM）。病毒产量抑制试验表明化合物10能够在病毒吸附之前和期间抑制HSV-1斑块的形成。在化合物处理过的细胞中观察到的特征性小噬斑图案表明，化合物10抑制了病毒向邻近细胞的传播。通过使用Lipinski规则确定亲脂性，拓扑极性表面积（TPSA），吸收率（％ABS）和简单分子描述符，对预测新型合成β-咔啉衍生物的ADME性质进行了计算研究。
• Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives
  作者：Anelise S. Nazari Formagio、Lilian T. Düsman Tonin、Mary Ann Foglio、Christiana Madjarof、João Ernesto de Carvalho、Willian Ferreira da Costa、Flávia P. Cardoso、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2008.10.008

  日期：2008.11

  Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50) < 100 mu M) for all eight different types of human cancer cell lines tested. The b-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI50 values lying in the nanomolar concentration range (GI(50) = 10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50) = 0.06 mu M), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents. (C) 2008 Elsevier Ltd. All rights reserved.