3-氰基-2-氧代丙酸乙酯钾盐 | 92664-05-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 3-氰基-2-氧代丙酸乙酯钾盐
• 英文名称: potassium 1-cyano-3-ethoxy-3-oxoprop-1-en-2-olate
• 英文别名: ethyl 3-cyano-2-(potassiooxy)prop-2-enoate；Potassium 1-cyano-3-ethoxy-2,3-dioxopropan-1-ide；potassium;ethyl 3-cyano-2-oxopropanoate
• CAS: 92664-05-6
• 化学式: C₆H₆NO₃*K
• 分子量: 179.217
• InChiKey: PIMPOWCURRWILD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.15
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  3-氰基-2-氧代丙酸乙酯钾盐 在 硫酸 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.25h， 生成 ethyl 2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-6-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis

  摘要：

  Taking into account the structure activity relationship information given by our previous studies, we designed and synthesized a small library of pyrazolylureas and imidazopyrazolecarboxamides fluorinated on urea moiety and differently decorated on pyrazole nucleus. All compounds were preliminary screened by Western blotting technique to evaluate their activity on MAPK and PI3K pathways by monitoring ERK1/2, p38MAPK and Akt phosphorylation, and also screened with a wound healing assay to assess their capacity in inhibiting endothelial cell migration, using human umbilical vein endothelial cells stimulated with VEGF. Pyrazoles and imidazopyrazoles did not show the same activity profile. SAR consideration showed that specific substituents and their position in pyrazole nucleus, as well as the type of substituent on the phenylurea moiety play a pivotal role in determining increase or decrease of kinases phosphorylation. On the other hand the loss of flexibility in imidazopyrazole derivatives is responsible for activity potentiation. Screening of the compound library for inhibition of endothelial cell migration, a function required for angiogenesis, showed significant activity for compound 3. This compound might interfere with cell migration by modulating the activity of different upstream target kinases. Therefore, compound 3 represents a potential inhibitor of angiogenesis. Furthermore, it may be used as a tool to identify unknown mediators of endothelial migration and thereby unveiling new therapeutic targets for controlling pathological angiogenesis in diseases such as cancers. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.066
• 作为产物：
  描述：

  草酸二乙酯 、 乙腈 在 18-冠醚-6 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以85%的产率得到3-氰基-2-氧代丙酸乙酯钾盐
  参考文献：
  名称：

  通过突变合成具有抗Hsp特性的新型格尔德霉素衍生物。

  摘要：

  用21种芳香族和杂芳香族氨基酸对格达那霉素生产商的吸湿链霉菌AHBA封闭突变株进行突变合成补充，提供了新的非喹诺酮类格尔德霉素衍生物。大规模（5 L）发酵提供了足够数量的四个新衍生物，足以进行完整的结构表征。在这些中，复生素的第一个噻吩衍生物对几种人类癌细胞系显示出强大的抗增殖活性。此外，观察到对人热休克蛋白Hsp90α和幽门螺杆菌HpHtpG细菌热休克蛋白的抑制作用，揭示了标记ATP的强置换性能，证明了Hsps的ATP结合位点是新格尔德霉素衍生物的目标位点。

  DOI：

  10.1039/c9ob00892f

文献信息

• HETEROCYCLIC INHIBITORS OF MCT4
  申请人：Vettore, LLC

  公开号：US20180162822A1

  公开（公告）日：2018-06-14

  Disclosed herein are compounds and compositions useful in the treatment of MCT4 mediated diseases, such as proliferative and inflammatory diseases, having the structure of Formula I: Methods of inhibition MCT4 activity in a human or animal subject are also provided.

  本文披露了一些化合物和组合物，适用于治疗由MCT4介导的疾病，如增殖性和炎症性疾病，其结构如下所示： 还提供了在人类或动物主体中抑制MCT4活性的方法。
• [EN] ALKYNYL ALCOHOLS AND METHODS OF USE<br/>[FR] ALCOOLS D'ALCYNYLE ET PROCÉDÉS D'UTILISATION CORRESPONDANTS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015025025A1

  公开（公告）日：2015-02-26

  The invention relates to compounds of Formula (0): wherein Q, A1-A8, R4 and R5 and each has the meaning as described herein. Compounds of Formula (0) and pharmaceutical compositions thereof are useful in the treatment of diseases and disorders in which undesired or over- activation of NF-kB signaling is observed.

  这项发明涉及以下式的化合物（0）：其中Q，A1-A8，R4和R5分别具有如本文所述的含义。式（0）的化合物及其药物组成物在治疗观察到NF-kB信号通路的不良或过度活化的疾病和紊乱中是有用的。
• [EN] TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE LA TRIAZINE ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：ABRAXIS BIOSCIENCE LLC

  公开号：WO2010144359A1

  公开（公告）日：2010-12-16

  Compounds of the formula (I) and formula (II) and pharmaceutically acceptable salts thereof.

  式(I)和式(II)的化合物及其药用盐。
• AZA-ARYL 1H-PYRAZOL-1-YL BENZENE SULFONAMIDES
  申请人：ChemoCentryx, Inc.

  公开号：US20180009797A1

  公开（公告）日：2018-01-11

  Compounds are provided that act as potent antagonists of the CCR(9) receptor for treating Sjogren's syndrome. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions.

  提供了作为治疗Sjogren综合征的CCR(9)受体的有效拮抗剂的化合物。这些化合物通常是芳基磺酰胺衍生物，并且在制药组合物中很有用。
• Insights into the Pharmacological Activity of the Imidazo−Pyrazole Scaffold
  作者：Andrea Spallarossa、Federica Rapetti、Maria Grazia Signorello、Camillo Rosano、Erika Iervasi、Marco Ponassi、Chiara Brullo

  DOI：10.1002/cmdc.202300252

  日期：2023.9

  In previous studies, we synthesized different imidazo−pyrazoles 1 and 2 with interesting anticancer, anti‐angiogenic and anti‐inflammatory activities. To further extend the structure‐activity relationships of imidazo−pyrazole scaffold and to identify novel antiproliferative/anti‐inflammatory agents potentially active with multi‐target mechanisms, a library of compounds 3–5 has been designed and synthesized. The chemical modifications characterizing the novel derivatives include: i) decoration of the catechol ring with groups with different electronic, steric and lipophilic properties (compounds 3); ii) insertion of a methyl group on C‐6 of imidazo−pyrazole scaffold (compounds 4); iii) shift of the acylhydrazonic substituent from position 7 to 6 of the imidazo−pyrazole substructure (compounds 5). All synthesized compounds were tested against a panel of cancer and normal cell lines. Derivatives 3 a, 3 e, 4 c, 5 g and 5 h showed IC₅₀ values in the low micromolar range against selected tumor cell lines and proved to have antioxidant properties, being able to inhibit ROS production in human platelet. In silico calculation predicted favourable drug‐like and pharmacokinetic properties for the most promising compounds. Furthermore, molecular docking and molecular dynamic simulations suggested the ability of most active derivative 3 e to interact with colchicine binding site in the polymeric tubulin α/tubulin β/stathmin4 complex.

  摘要 在之前的研究中，我们合成了不同的咪唑吡唑 1 和 2，它们具有有趣的抗癌、抗血管生成和抗炎活性。为了进一步扩展咪唑吡唑支架的结构-活性关系，并鉴定具有多靶点机制的潜在活性的新型抗增殖/抗炎剂，我们设计并合成了化合物库 3-5。这些新型衍生物的化学修饰特征包括：i）用具有不同电子、立体和亲油特性的基团装饰儿茶酚环（化合物 3）；ii）在咪唑吡唑支架的 C-6 上插入一个甲基（化合物 4）；iii）将酰肼取代基从咪唑吡唑子结构的第 7 位移到第 6 位（化合物 5）。对所有合成的化合物都进行了癌症和正常细胞系的测试。衍生物 3 a、3 e、4 c、5 g 和 5 h 对所选肿瘤细胞系的 IC50 值均在较低的微摩尔范围内，并证明具有抗氧化特性，能够抑制人体血小板中 ROS 的产生。硅学计算预测，最有前途的化合物具有良好的类药物和药代动力学特性。此外，分子对接和分子动力学模拟表明，最有活性的衍生物 3 e 能够与聚合管蛋白 α/tubulin β/stathmin4 复合物中的秋水仙碱结合位点相互作用。