3-(3-1H-indol-3-yl-acryloylamino)-benzoic acid methyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3-1H-indol-3-yl-acryloylamino)-benzoic acid methyl ester
• 英文别名: methyl 3-[[(E)-3-(1H-indol-3-yl)prop-2-enoyl]amino]benzoate
• 化学式: C₁₉H₁₆N₂O₃
• 分子量: 320.348
• InChiKey: JXFLQSAKYWHDIN-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-1H-indol-3-yl-acryloylamino)-benzoic acid methyl ester 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 C₂₄H₁₉N₃O₂
  参考文献：
  名称：

  发现吲哚基丙烯酰胺衍生物作为人类二酰基甘油酰基转移酶2选择性抑制剂†

  摘要：

  合成了一系列吲哚基丙烯酰胺衍生物，作为潜在的二酰基甘油酰基转移酶（DGAT）抑制剂。 糠胺含有吲哚基丙烯酰胺衍生物5h的化合物，用从大鼠肝脏制备的微粒体，对DGAT的抑制作用最强。确定了针对人类DGAT-1和DGAT-2的进一步评估吲哚基丙烯酰胺类似物作为针对人DGAT-2的选择性抑制剂。此外，最有效的化合物5h在HepG2细胞系中剂量依赖性地抑制了甘油三酸酯的合成。

  DOI：

  10.1039/c2ob27114a
• 作为产物：
  描述：

  3-氨基苯甲酸甲酯 、 反式吲哚-3-烯丙酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.83h， 以40%的产率得到3-(3-1H-indol-3-yl-acryloylamino)-benzoic acid methyl ester
  参考文献：
  名称：

  发现吲哚基丙烯酰胺衍生物作为人类二酰基甘油酰基转移酶2选择性抑制剂†

  摘要：

  合成了一系列吲哚基丙烯酰胺衍生物，作为潜在的二酰基甘油酰基转移酶（DGAT）抑制剂。 糠胺含有吲哚基丙烯酰胺衍生物5h的化合物，用从大鼠肝脏制备的微粒体，对DGAT的抑制作用最强。确定了针对人类DGAT-1和DGAT-2的进一步评估吲哚基丙烯酰胺类似物作为针对人DGAT-2的选择性抑制剂。此外，最有效的化合物5h在HepG2细胞系中剂量依赖性地抑制了甘油三酸酯的合成。

  DOI：

  10.1039/c2ob27114a

文献信息

• NOVEL LOW-MOLECULAR-COMPOUND FOR IMPROVING PRODUCTION, MAINTENANCE AND PROLIFERATION OF PLURIPOTENT STEM CELLS, COMPOSITION COMPRISING THE SAME, AND CULTURE METHOD
  申请人：KOREA RESEARCH INSTITUTE OF BIOSCIENCE AND BIOTECHNOLOGY

  公开号：US20150159142A1

  公开（公告）日：2015-06-11

  According to the present invention, when the novel low-molecular-weight compound RSC-133 is added in a culture process for producing reprogrammed pluripotent stem cells from human differentiated cells, it can increase the efficiency of reprogramming and can significantly reduce the time required for the induction of reprogramming. Particularly, the novel compound RSC-133 can substitute for c-Myc acting as both a reprogramming factor and an oncogenic factor, and it can effectively increase the efficiency of reprogramming in both normal oxygen culture conditions and hypoxic culture conditions. In addition, RSC-133 can inhibit the induction of aging occurring in the reprogramming process, exhibits the effect of promoting cell proliferation, and induces epigenetic activation to improve culture conditions for induction of reprogramming. The present invention will contribute to optimizing a process of producing induced pluripotent stem cells from a small amount of patient-specific somatic cells obtained from various sources, and thus it will significantly improve a process of developing clinically applicable personalized stem cell therapy agents and new drugs and will facilitate the practical use of these agents and drugs. In addition, the novel low-molecular-weight compound RSC-133 can provide a cell culture medium effective for maintaining the undifferentiated state of human embryonic stem cells that are typical pluripotent stem cells. The medium composition containing RSC-133 can effectively induce the proliferation of human embryonic stem cells in an undifferentiated state and can be effectively used for the development of a system for culturing large amounts of embryonic stem cells.

  根据本发明，当在从人类分化细胞生产重编程的多能干细胞的文化过程中添加新型的低分子量化合物RSC-133时，它可以提高重编程的效率，并且可以显著减少诱导重编程所需的时间。特别是，新型化合物RSC-133可以替代作为重编程因子和致癌因子的c-Myc，并且可以在正常氧文化条件和无氧文化条件下有效地提高重编程的效率。此外，RSC-133可以抑制在重编程过程中发生的衰老诱导，表现出促进细胞增殖的效果，并诱导表观遗传激活以改善重编程诱导的培养条件。本发明将有助于优化从各种来源获得的患者特异性体细胞的小量生产诱导多能干细胞的过程，从而将显著改进开发临床应用的个人化干细胞治疗剂和新药的过程，并将促进这些剂和药物的实用化。另外，新型的低分子量化合物RSC-133可以提供一个有效的细胞培养介质，用于维持典型多能干细胞的人胚胎干细胞的不分化状态。含有RSC-133的培养基质可以有效诱导人胚胎干细胞在不分化状态的增殖，并且可以有效地用于大量胚胎干细胞培养系统的开发。
• A Novel Small Molecule Facilitates the Reprogramming of Human Somatic Cells into a Pluripotent State and Supports the Maintenance of an Undifferentiated State of Human Pluripotent Stem Cells
  作者：Jungwoon Lee、Yan Xia、Mi-Young Son、Guanghai Jin、Binna Seol、Min-Jeong Kim、Myung Jin Son、Misol Do、Minho Lee、Dongsup Kim、Kyeong Lee、Yee Sook Cho

  DOI：10.1002/anie.201206691

  日期：2012.12.7

  acid/indolepropionic acid, exhibits dual activity by inhibiting histone deacetylase and DNA methyltransferase. Furthermore it potently improves the reprogramming of human somatic cells into a pluripotent state and aids the growth and maintenance of human pluripotent stem cells (hPSCs).

  多能性增强剂：吲哚丙烯酸/吲哚丙酸的新型合成衍生物RSC133通过抑制组蛋白脱乙酰酶和DNA甲基转移酶表现出双重活性。此外，它有效地改善了人类体细胞重编程为多能状态，并有助于人类多能干细胞（hPSC）的生长和维持。
• INDOL DERIVATIVES, THE METHOD FOR PREPARING THEREOF AND COMPOSITION FOR THE PREVENTION AND TREATMENT OF METABOLIC DISORDER CONTAINING THE SAME AS AN ACTIVE INGREDIENT
  申请人：Lee Kyeong

  公开号：US20100075962A1

  公开（公告）日：2010-03-25

  Disclosed are indole derivatives a preparation method thereof, and a composition for the prevention and treatment of metabolic diseases, containing the same as an active ingredient. The indole derivatives have inhibitory activity against DGAT (diacylglycerol acyltransferase), which causes metabolic diseases such as obesity and diabetes in the process of lipid metabolism. With the ability to effectively control lipid metabolism and energy metabolism, the composition is thus useful in the prevention and treatment of metabolic diseases, such as obesity and diabetes.

  本发明涉及吲哚衍生物及其制备方法，以及包含其作为活性成分的预防和治疗代谢性疾病的组合物。所述吲哚衍生物具有对DGAT（二酰基甘油酰基转移酶）的抑制活性，在脂质代谢过程中引起代谢性疾病，如肥胖和糖尿病。由于具有有效控制脂质代谢和能量代谢的能力，因此该组合物对于预防和治疗肥胖和糖尿病等代谢性疾病是有用的。
• NOVEL LOW-MOLECULE COMPOUND FOR PROMOTING PLURIPOTENT STEM CELL GENERATION, MAINTENANCE, AND PROLIFERATION, AND COMPOSITION AND CULTURING METHOD CONTAINING SAME
  申请人：Korea Research Institute of Bioscience and Biotechology

  公开号：EP2774918A1

  公开（公告）日：2014-09-10

  According to the present invention, when the novel low-molecular-weight compound RSC-133 is added in a culture process for producing reprogrammed pluripotent stem cells from human differentiated cells, it can increase the efficiency of reprogramming and can significantly reduce the time required for the induction of reprogramming. Particularly, the novel compound RSC-133 can substitute for c-Myc acting as both a reprogramming factor and an oncogenic factor, and it can effectively increase the efficiency of reprogramming in both normal oxygen culture conditions and hypoxic culture conditions. In addition, RSC-133 can inhibit the induction of aging occurring in the reprogramming process, exhibits the effect of promoting cell proliferation, and induces epigenetic activation to improve culture conditions for induction of reprogramming. The present invention will contribute to optimizing a process of producing induced pluripotent stem cells from a small amount of patient-specific somatic cells obtained from various sources, and thus it will significantly improve a process of developing clinically applicable personalized stem cell therapy agents and new drugs and will facilitate the practical use of these agents and drugs. In addition, the novel low-molecular-weight compound RSC-133 can provide a cell culture medium effective for maintaining the undifferentiated state of human embryonic stem cells that are typical pluripotent stem cells. The medium composition containing RSC-133 can effectively induce the proliferation of human embryonic stem cells in an undifferentiated state and can be effectively used for the development of a system for culturing large amounts of embryonic stem cells.

  根据本发明，当新型低分子量化合物RSC-133被添加到从人类分化细胞生产重编程多能干细胞的培养过程中时，它可以提高重编程的效率，并能显著缩短诱导重编程所需的时间。特别是，新型化合物 RSC-133 可替代 c-Myc 同时作为重编程因子和致癌因子，在正常氧培养条件和低氧培养条件下都能有效提高重编程效率。此外，RSC-133 还能抑制重编程过程中出现的老化诱导，具有促进细胞增殖的作用，并能诱导表观遗传活化，改善诱导重编程的培养条件。本发明将有助于优化从各种来源获得的少量患者特异性体细胞中生产诱导多能干细胞的过程，从而显著改善临床适用的个性化干细胞治疗药物和新药的开发过程，并促进这些药物和新药的实际应用。此外，新型低分子量化合物 RSC-133 还能提供一种细胞培养基，有效维持作为典型多能干细胞的人类胚胎干细胞的未分化状态。含有 RSC-133 的培养基组合物能有效诱导处于未分化状态的人类胚胎干细胞增殖，可有效用于开发培养大量胚胎干细胞的系统。
• Low-molecular-compound for improving production, maintenance and proliferation of pluripotent stem cells, composition comprising the same, and culture method
  申请人：Korea Research Institute of Bioscience and Biotechnology

  公开号：US10301598B2

  公开（公告）日：2019-05-28

  Provided herein are novel indoleacrylic acid-based compounds, and pharmaceutically acceptable salts thereof, useful for the production, maintenance and proliferation of pluripotent stem cells. Also provided are cell culture compositions comprising these compounds, and methods of using these compounds in the production and maintenance of pluripotent stem cells.

  本文提供了新型吲哚丙烯酸基化合物及其药学上可接受的盐类，可用于多能干细胞的生产、维持和增殖。还提供了包含这些化合物的细胞培养组合物，以及使用这些化合物生产和维持多能干细胞的方法。