(3S)-1-ethyl-1,2,3,4-tetrahydro-β-carboline 3-carboxylic acid | 191279-45-5

• 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-ethyl-1,2,3,4-tetrahydro-β-carboline 3-carboxylic acid
• 英文别名: (3S)-1-ethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
• CAS: 191279-45-5
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: OOJCKCNYTLTQGT-KFJBMODSSA-N

物化性质

• 沸点：
  492.2±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S)-1-ethyl-1,2,3,4-tetrahydro-β-carboline 3-carboxylic acid 在 氯化亚砜 、 sulfur 、 sodium hydroxide 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 水 为溶剂， 反应 1.0h， 生成 1-ethyl-9H-pyrido [3,4-b]indole-3-carboxylic acid
  参考文献：
  名称：

  Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer’s disease

  摘要：

  A series of tacrine-(beta-carboline) hybrids (11a-q) were designed, synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (BuChE) and self-induced beta-amyloid (A beta) aggregation, Cu2+-induced A beta (1-42) aggregation, and to chelate metal ions. Especially, 11l presented the greatest ability to inhibit cholinesterase (IC50, 21.6 nM for eeAChE, 63.2 nM for hAChE and 39.8 nM for BuChE), good inhibition of A beta aggregation (65.8% at 20 mu M) and good antioxidant activity (1.57 trolox equivalents). Kinetic and molecular modeling studies indicated that 11l was a mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 11l could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). These results suggested that 11l might be an excellent multifunctional agent for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.08.035
• 作为产物：
  描述：

  丙醛 、 L-色氨酸 在 硫酸 作用下， 以 水 为溶剂， 反应 24.0h， 生成 (3S)-1-ethyl-1,2,3,4-tetrahydro-β-carboline 3-carboxylic acid
  参考文献：
  名称：

  1-氨基甲酰基β-咔啉作为抗真菌新候选药物的发现和初步机制

  摘要：

  天然β-咔啉生物碱是发现重要药物实体的理想模型。各种 1-取代的β-咔啉是由商业上廉价的色氨酸合成的，并在体外对禾谷菌具有显着的抗真菌活性。值得注意的是， 与 Silthiopham (EC 50  = 8.95 μM)相比，在 1 位具有甲酰胺的化合物4m (EC 50 = 0.45 μM) 显示出最佳功效和近 20 倍的抗真菌潜力增强。此外，化合物6，7和4I显示出优异的体外抗真菌活性以及针对B. cinerea和F. graminearum 的体内保护和治疗活性。初步机制研究表明，化合物4m导致活性氧积累、细胞膜破坏和组蛋白乙酰化失调。这些发现表明 1-氨基甲酰基β-咔啉可以作为发现新型广谱杀菌剂候选物的有前途的模型。

  DOI：

  10.1016/j.ejmech.2021.113563

文献信息

• <i>Cis</i>-Diastereoselectivity in Pictet-Spengler Reactions of<scp>L</scp>-Tryptophan and Electronic Circular Dichroism Studies
  作者：Naghmana Rashid、Samina Alam、Mashooda Hasan、Naeema Khan、Khalid M. Khan、Helmut Duddeck、Gennaro Pescitelli、Ágnes Kenéz、Sándor Antus、Tibor Kurtán

  DOI：10.1002/chir.22070

  日期：2012.10

  The diastereoselective synthesis of optically active 1,3‐disubstituted tetrahydro‐β‐carbolines using polar protic Pictet–Spengler cyclization of (S)‐tryptophan methyl ester with five aldehydes RCHO (R═CH3, C2H5, C3H7, C4H9, and C6H5) was studied. As an alternate route, the cyclization of (S)‐tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro‐β‐carboline carboxylic

  光学活性的1,3-二取代使用（的极性质子的Pictet Spengler环化生成四氢β咔啉的非对映选择性合成小号） -色氨酸甲酯五醛RCHO（R = CH 3，C 2 H ^ 5，C 3 H ^ 7，C 4 H 9和C 6 H 5）进行了研究。作为替代方法，还进行了将（S）-色氨酸与相同的醛环化，然后将所得的四氢-β-咔啉羧酸进行甲基化的比较。13C NMR和电子圆二色性（ECD）研究以及随时间变化的密度泛函理论ECD计算数据确定了合成化合物的相对1,3顺式/反式和绝对构型（1 S，3 S / 1 R，3 S） 。对制备的化合物进行的固态和溶液ECD研究，得到ECD计算和X射线数据的支持，为1,3-二取代四氢-β-咔啉的构型分配提供了可靠的ECD方法，并揭示了决定化学反应的立体化学因素。典型的ECD数据。手性24：789–795，2012。分级为4 +©2012 Wiley Periodicals，Inc
• Synthesis and Antitumor Activity of Javacarboline Derivatives
  作者：Tamotsu Nikaido、Hiroshi Yoshino、Kazuo Koike

  DOI：10.3987/com-98-8378

  日期：——
• 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 in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives
  作者：Rihui Cao、Wenlie Peng、Hongsheng Chen、Xuerui Hou、Huaji Guan、Qi Chen、Yan Ma、Anlong Xu

  DOI：10.1016/j.ejmech.2004.11.005

  日期：2005.3

  A series of novel 1,3-bisubstituted and 1, 3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material L-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1,3-bisubstituted compounds. Among all the synthesized 1,3,9-trisubstituted P-carboline derivatives, the compounds with a methyl substituent at position-1 displayed more potent cytotoxic activities, furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a pentafluorobenzyl at position-9, respectively, was found to be the most potent compounds of this series with IC50 value of 4 uM against BGC-823 cell lines. These data suggested that (1) the cytotoxic potencies of beta-carboline derivatives were enhanced by the introduction of appropriate substituents into position-1 and position-9 in beta-carboline; (2) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs; (3) the methyl substituent at position-1, the pentafluorobenzyl group at position-9 and the ethoxycarbonyl substituent at position-3 were the optimal combination for the improvement of cytotoxic activity of the P-carboline derivatives. (c) 2004 Elsevier SAS. All rights reserved.
• Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer’s disease
  作者：Jin-Shuai Lan、Sai-Sai Xie、Su-Yi Li、Long-Fei Pan、Xiao-Bing Wang、Ling-Yi Kong

  DOI：10.1016/j.bmc.2014.08.035

  日期：2014.11

  A series of tacrine-(beta-carboline) hybrids (11a-q) were designed, synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (BuChE) and self-induced beta-amyloid (A beta) aggregation, Cu2+-induced A beta (1-42) aggregation, and to chelate metal ions. Especially, 11l presented the greatest ability to inhibit cholinesterase (IC50, 21.6 nM for eeAChE, 63.2 nM for hAChE and 39.8 nM for BuChE), good inhibition of A beta aggregation (65.8% at 20 mu M) and good antioxidant activity (1.57 trolox equivalents). Kinetic and molecular modeling studies indicated that 11l was a mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 11l could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). These results suggested that 11l might be an excellent multifunctional agent for AD treatment. (C) 2014 Elsevier Ltd. All rights reserved.