N-(2-(1H-indol-3-yl)ethyl)-2-aminoacetamide | 122902-82-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-(1H-indol-3-yl)ethyl)-2-aminoacetamide
• 英文别名: tryptamine glycnamide；glycine tryptamide；Glycyltryptamine；2-amino-N-[2-(1H-indol-3-yl)ethyl]acetamide
• CAS: 122902-82-3
• 化学式: C₁₂H₁₅N₃O
• mdl: MFCD08282638
• 分子量: 217.271
• InChiKey: APXFWBYFEVCORP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.9
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P305+P351+P338,P332+P313,P337+P313,P362
• 危险性描述：
  H315,H319
• 储存条件：
  室温、密闭保存，并确保干燥。

反应信息

• 作为反应物：
  描述：

  N-(2-(1H-indol-3-yl)ethyl)-2-aminoacetamide 在 4-二甲氨基吡啶 、 sodium methylate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 96.08h， 生成 (E)-3-(4-hydroxyphenyl)-N-[2-[2-(1H-indol-3-yl)ethylamino]-2-oxoethyl]prop-2-enamide
  参考文献：
  名称：

  N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors

  摘要：

  A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.023
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-glycine tryptamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以99%的产率得到N-(2-(1H-indol-3-yl)ethyl)-2-aminoacetamide
  参考文献：
  名称：

  N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors

  摘要：

  A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.023

文献信息

• Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer’s disease
  作者：Yash Pal Singh、Gauri Shankar、Shagufta Jahan、Gourav Singh、Navneet Kumar、Atanu Barik、Prabhat Upadhyay、Lovejit Singh、Kajal Kamble、Gireesh Kumar Singh、Sanjay Tiwari、Prabha Garg、Sarika Gupta、Gyan Modi

  DOI：10.1016/j.bmc.2021.116385

  日期：2021.9

  of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC50 = 0.96 ± 0.14 µM, BChE IC50 = 1.23 ± 0.23 µM) compared to earlier identified lead molecule EJMC-G (AChE

  在我们之前的论文中，我们描述了基于阿魏酸 ( FA ) 模板的新型多功能胆碱酯酶 (ChE) 抑制剂系列，用于治疗 AD。本报告以校准的方式进一步扩展了该系列分子的构效关系 (SAR) 研究，以提高对 ChE 的抑制和抗氧化性能，从而鉴定出新型强效多功能分子。研究用苄基哌嗪取代苯基哌嗪环的效果，增加FA之间的接头长度和取代苯环，并在该分子模板上用色胺取代吲哚部分，开发了三个系列的新分子。测试了所有合成化合物的乙酰胆碱酯酶和丁酰胆碱酯酶（AChE 和 BChE）抑制特性。酶抑制和PAS结合研究鉴定的化合物13B，为先导分子朝向乙酰胆碱酯酶/ BChE的强效抑制剂属性胆碱酯酶（AChE的IC 50 = 0.96±0.14 μ男，IC的BChE 50 = 1.23±0.23 μ M）相比，先前确定先导分子EJMC- G（AChE IC 50 = 5.74 ± 0.13 μ M，BChE IC 50
• Application of Fragment-Based de Novo Design to the Discovery of Selective Picomolar Inhibitors of Glycogen Synthase Kinase-3 Beta
  作者：Hwangseo Park、Yongje Shin、Jinhee Kim、Sungwoo Hong

  DOI：10.1021/acs.jmedchem.6b00944

  日期：2016.10.13

  systematic fragment-based de novo design procedure was developed and applied to discover new potent and selective inhibitors of glycogen synthase kinase-3 beta (GSK3β). Candidate inhibitors were generated to simultaneously maximize the biochemical potency and the specificity for GSK3β through three design steps: identification of the optimal molecular fragments for the three sub-binding regions, design of

  开发了基于系统片段的从头设计程序，并将其应用于发现糖原合酶激酶-3β（GSK3β）的新的有效和选择性抑制剂。通过三个设计步骤生成候选抑制剂，以同时最大化GSK3β的生化效能和特异性：鉴定三个亚结合区的最佳分子片段，设计适当的连接部分以连接片段结构单元，以及对GSK3β的最终评分产生的分子。通过使用混合标度粒子理论和扩展的溶剂接触模型修改评分功能中的配体水合自由能术语，我们确定了几种GSK3β抑制剂，其生化潜能范围从低纳摩尔到皮摩尔水平。其中，两种最有效的抑制剂（12和27）预计将作为有希望的药物发现为因为高特异性GSK3β的抑制引起的GSK3β的各种疾病的起始点。
• 질소 함유 헤테로아릴 유도체 및 GSK3β 저해제로서의 이의 용도
  申请人：INSTITUTE FOR BASIC SCIENCE 기초과학연구원(120120549213) Corp. No ▼ 160171-0006707BRN ▼314-82-15276

  公开号：KR101746199B1

  公开（公告）日：2017-06-13

  본 발명은 GSK3β 저해 활성을 갖는 신규한 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 제공한다. [화학식 1] 상기 화학식 1에서, X는 탄소(C) 또는 질소(N)이고; Y는 탄소(C) 또는 산소(O)이며; R은 수소, 아릴, -CO-아릴 또는 헤테로아릴이며, 이때 상기 아릴 또는 헤테로아릴은 치환되지 않거나 또는 치환될 수 있고; R는 -CO-NH-(CH)-CO-NH-, -CO-O-(CH)-, -CH=CH-(CH)-CO-NH- 또는 -(CH)-CO-NH-이며, 이때 n은 1 내지 3의 정수이고 m은 0 내지 3의 정수이며; R는 C알킬, -(CH)-아릴, -(CH)-헤테로아릴 또는 -(CH)-헤테로사이클릴이고, 이때 상기 아릴, 헤테로아릴 또는 헤테로사이클릴은 치환되지 않거나 또는 치환될 수 있다. 상기 화학식 1의 화합물은 GSK3β와 연관된 질환, 즉 증식성 질환, 신경 변성 또는 신경성 질환, 염증성 자가면역질환, 심혈관 질환, 내분비 질환, 및 바이러스 감염 질환을 예방 또는 치료하는데 유용하다.

  本发明提供了一种具有GSK3β抑制活性的新化合物的化学式1或其药学上可接受的盐。[化学式1] 在上述化学式1中，X为碳（C）或氮（N）; Y为碳（C）或氧（O）; R为氢，芳基，-CO-芳基或杂环芳基，其中所述芳基或杂环芳基可以是未取代或取代的; R为-CO-NH-(CH)-CO-NH-, -CO-O-(CH)-, -CH=CH-(CH)-CO-NH-或-(CH)-CO-NH-，其中n为1到3的整数，m为0到3的整数; R为C烷基，-(CH)-芳基，-(CH)-杂环芳基或-(CH)-杂环烷基，其中所述芳基，杂环芳基或杂环烷基可以是未取代或取代的。上述化学式1的化合物对与GSK3β相关的疾病，如增殖性疾病，神经变性或神经性疾病，炎症性自身免疫疾病，心血管疾病，内分泌疾病和病毒感染性疾病的预防或治疗是有用的。
• Identification of lead small molecule inhibitors of glycogen synthase kinase-3 beta using a fragment-linking strategy
  作者：Jinhee Kim、Yonghoon Moon、Sungwoo Hong

  DOI：10.1016/j.bmcl.2016.10.060

  日期：2016.12

  Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six-atom chain unit bearing the rigid double bond was found to be a suitable linker connecting two fragments, which enables favorable contacts with backbone groups of residues in the pockets. As a consequence, potent GSK3β inhibitor 9i was found with IC50 values

  糖原合酶激酶3β（GSK3β）激酶可作为治疗各种人类疾病（如糖尿病，肥胖症和阿尔茨海默氏病）的有希望的治疗靶标。在这项研究中，我们报告了使用片段连接策略鉴定出的主要GSK3β抑制剂。通过系统的探索，发现带有刚性双键的六原子链单元是连接两个片段的合适连接基，可实现与口袋中残基的骨架基团的良好接触。结果，发现有效的GSK3β抑制剂9i的IC50值为19nM。结合模式分析表明，抑制剂的活性似乎是通过在GSK3β的ATP结合位点建立多个氢键和疏水相互作用来实现的。
• Butenolide and pentenolide derivatives as kinase inhibitors
  申请人：——

  公开号：US20040102488A1

  公开（公告）日：2004-05-27

  The present invention relates to new compounds of the general formula (I), 1 to methods for their preparation, and to pro-drugs, pharmacologically acceptable salts and medicamental compositions comprising them as active ingredient, and to their use as kinase inhibitors.

  本发明涉及通式(I)的新化合物、 1 及其制备方法，以及包含它们作为活性成分的原药、药理学上可接受的盐类和药物组合物，以及它们作为激酶抑制剂的用途。