2-cyano-N-(3-(4-morpholinyl)propyl)acetamide | 15029-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-cyano-N-(3-(4-morpholinyl)propyl)acetamide
• 英文别名: 2-cyano-N-(3-morpholinopropyl)acetamide；N-(3-Morpolino-propyl)-cyanacetamid；2-cyano-N-(3-morpholin-4-yl-propyl)-acetamide；Acetamide, 2-cyano-N-[3-(4-morpholinyl)propyl]-；2-cyano-N-(3-morpholin-4-ylpropyl)acetamide
• CAS: 15029-27-3
• 化学式: C₁₀H₁₇N₃O₂
• 分子量: 211.264
• InChiKey: IFXUPQLGROKDRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyano-N-(3-(4-morpholinyl)propyl)acetamide 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 16.5h， 生成 Ethyl 5-methyl-3-(3-morpholin-4-ylpropyl)-4-oxothieno[3,4-d]pyrimidine-7-carboxylate
  参考文献：
  名称：

  摘要：

  Approaches to the synthesis of 3-aminothiophene-2,4-dicarboxylic acid derivatives and to their conversions into thieno[3,4-d]pyrimidines, thieno[3,4-d]-1,2,3-triazines, and thieno[3,2-d]pyrimidines are developed.

  DOI：

  10.1023/a:1016049204323
• 作为产物：
  描述：

  N-(3-氨丙基)吗啉 、 氰乙酸乙酯 以 neat (no solvent) 为溶剂， 反应 72.0h， 以88%的产率得到2-cyano-N-(3-(4-morpholinyl)propyl)acetamide
  参考文献：
  名称：

  SPOP抑制剂对肾脏癌的构效关系。

  摘要：

  在几乎所有的透明细胞肾细胞癌（ccRCC）中，斑点型POZ蛋白（SPOP）在细胞核中过度表达，并在细胞质中错位，从而导致肾脏肿瘤发生。先前，我们阐明了ccRCC中的致癌SPOP信号通路可能被抑制SPOP介导的蛋白质相互作用的6b所抑制。在这里，我们已经建立了6b类似物作为SPOP抑制剂的构效关系。化合物6lc抑制了活力，并抑制了优于6b的细胞质SPOP驱动的ccRCC细胞系的集落形成。化合物6lc在体外与SPOP蛋白结合，并破坏HEK293T细胞中SPOP与磷酸酶和肌腱蛋白同源物（PTEN）的结合，这引起了可观察到的现象：PTEN泛素化的下降，当ccRCC细胞系以剂量反应方式暴露于6lc时，PTEN和双重特异性磷酸酶7的水平升高，磷酸化AKT和ERK的水平降低。两者合计，化合物6lc是对抗肾肿瘤发生的有效候选物。

  DOI：

  10.1021/acs.jmedchem.0c00161

文献信息

• Synthesis of resveratrol acrylamides derivatives and biological evaluation of their anti-proliferative effect on cancer cell lines
  作者：Ban-Feng Ruan、Si-Qi Wang、Xiao-Lin Ge、Ri-Sheng Yao

  DOI：10.2174/15701808113109990057

  日期：2013.11

  A new series of resveratrol acrylamides amine derivatives was designed, synthesized, and evaluated for their anti-proliferative activity against three cancer cell lines including human chronic myelocytic leukemia cell K562, human hepatoma HuH-7 and human lung carcinoma A549. Most of the compounds showed superior activity against three cell lines when compared to parent resveratrol. C13 had the best anti-tumor activity against the HuH-7 cell line and its IC50 was 4.5 μmol/L; C16 had the best anti-tumor activity against the K562 cell line and its IC50 was 2.9 μmol/L; C18 had the best anti-tumor activity against the A549 cell line and its IC50 was 3.8 μmol/L. It could be seen that the activity of the aromatic amine derivatives was better than the fatty amine derivatives by analyzing the experimental data.

  设计、合成并评价了一系列白藜芦醇丙烯酰胺胺衍生物对三种癌细胞株的抗增殖活性，包括人慢性髓细胞白血病细胞K562、人肝癌HuH-7和人肺癌A549。与母体白藜芦醇相比，大多数化合物对三种细胞株表现出更强的活性。C13对HuH-7细胞株具有最佳的抗肿瘤活性，其IC50为4.5 μmol/L; C16对K562细胞株具有最佳的抗肿瘤活性，其IC50为2.9 μmol/L；C18对A549细胞株具有最佳的抗肿瘤活性，其IC50为3.8 μmol/L。通过分析实验数据可以发现，芳香胺衍生物的活性优于脂肪胺衍生物。
• New C4- and C1-derivatives of furo[3,4-c]pyridine-3-ones and related compounds: Evidence for site-specific inhibition of the constitutive proteasome and its immunoisoform
  作者：Anna Hovhannisyan、The Hien Pham、Dominique Bouvier、Alexander Piroyan、Laure Dufau、Lixian Qin、Yan Cheng、Gagik Melikyan、Michèle Reboud-Ravaux、Michelle Bouvier-Durand

  DOI：10.1016/j.bmcl.2014.01.072

  日期：2014.3

  furo[3,4-c]pyridine-3-one), 6 model compounds (γ- and δ-lactones) and 20 furo- or thieno[2,3-d]-pyrimidine-4-one related compounds were designed and synthesized. Each compound was assayed for inhibition of CT-L, T-L and PA proteolytic activities of 20S constitutive proteasome (c20S). Most performant compounds were also assayed on 20S immunoproteasome (i20S). Compound 10 with a benzylamino group at C4

  一组18个新的去甲-头孢菌素（1,1-二甲基呋喃[3,4- c ]吡啶-3-一）的C 4和C 1衍生物，6个模型化合物（γ-和δ-内酯）和20个呋喃设计或合成了噻吩并[2,3- d ]-嘧啶-4-one相关化合物。测定每种化合物对20S组成型蛋白酶体（c20S）的CT-L，TL和PA蛋白水解活性的抑制。还可以在20S免疫蛋白酶体（i20S）上分析大多数性能良好的化合物。在呋喃吡啶环的C 4处有苄氨基并在C 1处二甲基化的化合物10是c20S的最有效的PA位点特异性抑制剂（我知道了50每次转化费用600 nM）不会显着抑制i20S PA位点（iPA）。在iPA催化位点的计算机对接分析中，对10个化合物的分析表明，通常在该组成性PA位点（cPA）上没有观察到该化合物及相关位姿。Thieno [2,3- d ]嘧啶-4-酮40具有TL位​​点特异性，在体外对c20S和i20S均具有轻度抑制作用（我知道了50脂蛋白
• 2-亚胺-5-酮基-2,5-二氢-1-H-二吡啶并嘧啶 类化合物
  申请人：中国科学院上海药物研究所

  公开号：CN107141287B

  公开（公告）日：2021-10-26

  本发明提供了一种2‑亚胺‑5‑酮基‑2,5‑二氢‑1‑H‑二吡啶并[3,4‑c:1’,2’‑f]嘧啶类化合物的合成及其用途，具体地，本发明公开了具有如下通式(I)所示的化合物，及其药学上可以接受的盐或药学上可以接受的溶剂合物，其中各基团的定义如说明书中所述。本发明的化合物可以作为以SPOP为靶点的抑制剂，或者制备治疗和/或预防以SPOP为靶点疾病(比如肾癌等)的药物。
• Cyanoacetamides (IV): Versatile One-Pot Route to 2-Quinoline-3-carboxamides
  作者：Kan Wang、Eberhardt Herdtweck、Alexander Dömling

  DOI：10.1021/co3000133

  日期：2012.5.14

  Cyanoacetic acid derivatives are the starting materials for a plethora of multicomponent reaction (MCR) scaffolds. Herein, we describe scope of a valuable general protocol for the synthesis of arrays of 2-aminoquinoline-3-carboxamides from cyanoacetamides and 2-aminobenzaldehydes or heterocyclic derivatives via a Friedlander reaction variation. In many cases, the reactions involve a very convenient work up by simple precipitation and filtration. More than 40 new products are described. We foresee our protocol and the resulting derivatives becoming very valuable to greatly expanding the scaffold space of cyanoacetamide derivatives.
• Discovery of chromenes as inhibitors of macrophage migration inhibitory factor
  作者：Tjie Kok、Hannah Wapenaar、Kan Wang、Constantinos G. Neochoritis、Tryfon Zarganes-Tzitzikas、Giordano Proietti、Nikolaos Eleftheriadis、Katarzyna Kurpiewska、Justyna Kalinowska-Tłuścik、Robbert H. Cool、Gerrit J. Poelarends、Alexander Dömling、Frank J. Dekker

  DOI：10.1016/j.bmc.2017.12.032

  日期：2018.3

  Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aim to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tautomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50's in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved. (C) 2017 Elsevier Ltd. All rights reserved.