ethyl-2-hydroxy-4-(3-thienyl)-4-oxo-2-butenoate | 1233131-24-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl-2-hydroxy-4-(3-thienyl)-4-oxo-2-butenoate
• 英文别名: 2-hydroxy-4-(thiophen-2-yl)-4-oxobut-2-enoic acid ethyl ester；Ethyl 2-hydroxy-4-oxo-4-thiophen-2-ylbut-2-enoate
• CAS: 1233131-24-2
• 化学式: C₁₀H₁₀O₄S
• mdl: MFCD09743371
• 分子量: 226.253
• InChiKey: ADGYUYIYYMFEES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl-2-hydroxy-4-(3-thienyl)-4-oxo-2-butenoate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.75h， 以76%的产率得到4-(thiophen-2-yl)-2-hydroxy-4-oxobut-2-enoic acid
  参考文献：
  名称：

  Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B polymerase inhibition

  摘要：

  Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Here we report the synthesis and biological evaluation of a new series of alpha,gamma-diketo acids (DKAs) as NS5B polymerase inhibitors. We initiated structure-activity relationship (SAR) optimization around the furan moiety of compound 1a [IC50 = 21.8 mu M] to achieve more active NS5B inhibitors. This yielded compound 3a [IC50 = 8.2 mu M] bearing the 5-bromobenzofuran-2-yl moiety, the first promising lead compound of the series. Varying the furan moiety with thiophene, thiazole and indazole moieties resulted in compound 11a [IC50 = 7.5 mu M] bearing 3-methylthiophen-2-yl moiety. Finally replacement of the thiophene ring with a bioisosteric phenyl ring further improved the inhibitory activity as seen in compounds 21a [IC50 = 5.2 mu M] and 24a [IC50 = 2.4 mu M]. Binding mode of compound 24a using glide docking within the active site of NS5B polymerase will form the basis for future SAR optimization. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.028
• 作为产物：
  描述：

  2-乙酰基噻吩 、 草酸二乙酯 在 sodium ethanolate 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 0.5h， 以93%的产率得到ethyl-2-hydroxy-4-(3-thienyl)-4-oxo-2-butenoate
  参考文献：
  名称：

  合成，表征，生物学活性，DNA和BSA结合研究：新型铜（ii）与2-羟基-4-芳基-4-氧代-2-丁烯酸酯的络合物†

  摘要：

  一系列新颖的方形金字塔型铜（II）配合物[Cu（L）2 H 2 O]（3a–d）与O，O-双齿配体[L =乙基-2-羟基-4-芳基-4-氧代- 2-丁烯酸酯; 芳基= 3-甲氧基苯基2A，（ê）-2- phenylvinyl- 2B，（ë）-2-（4'-羟基-3'-甲氧基苯基）乙烯基2C，3-硝基苯基2D，2-噻吩基- 2E合成并通过光谱（UV-Vis，IR，ESI-MS和EPR），元素分析和X射线分析对其进行表征。通过使用肉汤微量稀释法确定最小抑菌浓度（MIC）来评估抗菌活性。活性最高的抗菌化合物是3c和3d，而复合物3b和3e表现出最好的抗菌活性。测量了针对奇异变形杆菌的最低MIC值（0.048 mg mL -1）3c。使用MTT方法测试了对人上皮癌HeLa细胞，人肺癌A549细胞和人结肠癌LS174细胞的细胞毒性活性。在所有测试浓度下，与顺铂相比，所有复合物均显示出极佳的细胞毒活性。

  DOI：

  10.1039/c6dt02257j

文献信息

• [EN] APPETITE-MODULATING MOLECULES<br/>[FR] MOLÉCULES MODULATRICES DE L'APPÉTIT
  申请人：UNIV ZUERICH

  公开号：WO2020074403A1

  公开（公告）日：2020-04-16

  The present invention relates to small molecule compounds capable of modulating appetite in a vertebrate animal, particularly in a mammal. The invention further relates to the use of the compounds of the invention in methods of treatment of eating disorders, and as a food additive for human consumption or animal husbandry.

  本发明涉及能够调节脊椎动物食欲的小分子化合物，特别是哺乳动物。该发明还涉及将该化合物用于治疗进食障碍的方法，以及作为人类或动物饲养业的食品添加剂。
• Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis
  作者：Daniele Zampieri、Maria Grazia Mamolo、Julia Filingeri、Sara Fortuna、Alessandro De Logu、Adriana Sanna、Davide Zanon

  DOI：10.1016/j.bmcl.2019.07.025

  日期：2019.9

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.