(S)-1-(3-Nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester | 380895-65-8

• 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-(3-Nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
• CAS: 380895-65-8
• 化学式: C₁₉H₁₇N₃O₄
• 分子量: 351.362
• InChiKey: WTZMWVYGTPUZFA-BHWOMJMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.85
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.26
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-1-(3-Nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 在 2,3-二氯-5,6-二氰基-1,4-苯醌 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 1-(3-nitrophenyl)-9H-β-carboline-3-carboxylic acid
  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 硫酸 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 生成 (S)-1-(3-Nitro-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  新型杂种β-咔啉-4-噻唑烷酮类化合物的合成和评价作为潜在的抗肿瘤和抗病毒药

  摘要：

  合成了一系列新颖的杂种β-咔啉-4-噻唑烷酮，并评估了其对人癌细胞的体外抗肿瘤活性以及对单纯疱疹病毒1型（HSV-1）的抗病毒活性。从N' - （咪唑烷-2-亚基-4-噻唑烷酮） - β咔啉-3-碳酰肼系列（9-11），Ç ompounds 9C和11d中是最活跃的，表现出生长抑制50％（GI 50）的值小于对于所有测试的细胞系，均大于5μM 化合物9c中，轴承4 -二甲氨基苯基在C-1 β选择-咔啉来进行有关细胞死亡和细胞周期图的进一步研究，重点是人肾腺癌细胞系786-0。用25μM的化合物9c处理在处理15小时后会诱导细胞死亡，其特征在于磷脂酰丝氨酸的暴露和膜完整性的丧失。此外，用12.5μM的处理可促进亚G1阻滞，这表明细胞死亡。N-（2-取代-芳基-4-噻唑烷酮）-β-咔啉-3-羧酰胺系列（18-23）的衍生物显示出对神经胶质瘤（U251）和卵巢癌（OVCAR-3）的强活性和高选择

  DOI：

  10.1016/j.ejmech.2016.10.018

文献信息

• 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。
• 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.
• 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.
• Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids
  作者：Paula Baréa、Valéria Aquilino Barbosa、Danielle Lazarin Bidóia、Jéssica Carreira de Paula、Talitha Fernandes Stefanello、Willian Ferreira da Costa、Celso Vataru Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2018.03.014

  日期：2018.4

  A series of novel hybrids beta-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 mu M. Compounds 9e and 1611) were also active against amastigote forms, displaying IC50 values of 1.0 +/- 0.1 mu M and 1.2 +/- 0.51 mu M, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of beta-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Modified Pictet–Spengler reaction. A highly diastereoselective approach to 1,2,3-trisubstituted-1,2,3,4-tetrahydro-β-carbolines using perhydro-1,3-heterocycles
  作者：Kamaljit Singh、Prasant K Deb、P Venugopalan

  DOI：10.1016/s0040-4020(01)00763-3

  日期：2001.9

  A flexible variant of the Pictet-Spengler reaction employing oxazinanes as synthetic equivalents of several carbonyl compounds has been developed. Using acid catalyzed one pot condensation of perhydro-1,3-heterocycles various 1,3-disubstituted and 1,2,3-trisubstituted-1,2,3,4-tetrahydro-beta -carbolines (THBCs) have been synthesized diastereoselectively. (C) 2001 Elsevier Science Ltd. All rights reserved.