(3S)-1-(3-Nitrophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid | 1085709-23-4

• 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: (3S)-1-(3-Nitrophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid
• 英文别名: (3S)-1-(3-nitrophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
• CAS: 1085709-23-4
• 化学式: C₁₈H₁₅N₃O₄
• 分子量: 337.335
• InChiKey: CYXGKHWORVZUGJ-VYRBHSGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S)-1-(3-Nitrophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid 在 盐酸 、 sodium tetrahydroborate 、 potassium permanganate 、 氯化亚砜 、 羟胺钾盐 、 一水合肼 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 N-hydroxy-4-(((1-(3-nitrophenyl)-9H-pyrido[3,4-b]indol-3-yl)amino)methyl)benzamide
  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：

  间硝基苯甲醛 、 L-色氨酸 在 溶剂黄146 作用下， 反应 2.0h， 生成 (3S)-1-(3-Nitrophenyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid
  参考文献：
  名称：

  在C-3处带有取代的碳酰肼的β-咔啉衍生物的合成及其抗脊髓灰质炎病毒和单纯疱疹病毒（HSV-1）的活性

  摘要：

  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。

  DOI：

  10.1016/j.ejmech.2009.07.005

文献信息

• A convenient synthesis of β-carbolines by iron-catalyzed aerobic decarboxylative/dehydrogenative aromatization of tetrahydro-β-carbolines under air
  作者：Ahmad Saifuddin Mohamad Arshad、Ramu Meesala、Nur Aziah Hanapi、Mohd Nizam Mordi

  DOI：10.1016/j.tet.2021.131960

  日期：2021.3

  A convenient synthesis for the conversion of various substituted tetrahydro-β-carbolines has been developed by iron-catalyzed decarboxylative/dehydrogenative aromatization to construct aromatic β-carbolines under air atmosphere. In the presence of a FeCl3 catalyst, this reaction exhibited a good functional group tolerance to produce corresponding β-carbolines in good yields in the absence of any additive

  通过铁催化的脱羧/脱氢芳构化，在空气气氛下构建芳族β-咔啉，已经开发了一种方便的合成各种取代的四氢-β-咔啉的方法。在FeCl 3催化剂的存在下，该反应表现出良好的官能团耐受性，在不存在任何添加剂的情况下以高收率生产相应的β-咔啉。此外，该方法的实用性在重要的天然β-咔啉合成子正壬烷（2a）和harmane（2b）的克级合成中得到了强调，后者为实际生产eudistomin N和nostocarboline提供了便利。
• 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.
• 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.