4-(furan-2-yl)-2-hydroxy-4-oxobut-2-enoic acid | 521945-01-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(furan-2-yl)-2-hydroxy-4-oxobut-2-enoic acid
• 英文别名: 4-(Furan-2-yl)-4-hydroxy-2-oxobut-3-enoic acid
• CAS: 521945-01-7
• 化学式: C₈H₆O₅
• 分子量: 182.133
• InChiKey: WERKCHLFSAEFDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(furan-2-yl)-2-hydroxy-4-oxobut-2-enoic acid 、 2-氨基苯硫醇 在 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 以58%的产率得到(3Z)-3-(2-(furan-2-yl)-2-oxoethylidene)-3,4-dihydro-2H-1,4-benzothiazin-2-one
  参考文献：
  名称：

  Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

  摘要：

  通过呋喃-2,3-二酮或酰基丙酮酸在碳化二亚胺存在下与邻氨基苯硫酚的反应，我们开发了两种合成融合了 1,4-苯并噻嗪-2-酮分子的烯酰胺酮的方法，这些烯酰胺酮在生物活性、化学传感器和荧光研究方面具有重要意义。目标烯酮与具有药学意义的 2-羟基-2H-1,4-苯并噻嗪-3(4H)-酮一起形成。通过呋喃-2,3-二酮与邻氨基苯硫酚的溶剂切换反应，开发了一种 2-羟基-2H-1,4-苯并噻嗪-3(4H)-酮的选择性合成方法。对新化合物进行了初步的生物检测（抗菌、急性毒性）。

  DOI：

  10.3762/bjoc.16.193
• 作为产物：
  描述：

  ethyl 4-(furan-2-yl)-2-hydroxy-4-oxobut-2-enoate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.75h， 以72%的产率得到4-(furan-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

文献信息

• [EN] NMDA RECEPTOR MODULATORS AND USES RELATED THERETO<br/>[FR] MODULATEURS DE RÉCEPTEUR NMDA ET UTILISATIONS ASSOCIÉES À CEUX-CI
  申请人：UNIV EMORY

  公开号：WO2014025942A1

  公开（公告）日：2014-02-13

  This disclosure relates to NMDA modulators and used related thereto such as for treatment of central nervous system disorders. In certain embodiments, compounds disclosed herein are NR2C subunit-selective NMDA potentiators. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions. In certain embodiments, the disclosure contemplates compounds disclosed herein as prodrugs, optionally substituted with one or more substituents, derivatives, or salts thereof. In certain embodiments, the disclosure relates to methods of treating or preventing nervous system disorders comprising administering an effective amount of a composition comprising compound disclosed herein to a subject in need thereof.

  这份披露涉及NMDA调节剂及其相关用途，如用于治疗中枢神经系统疾病。在某些实施方式中，本文披露的化合物是NR2C亚基选择性NMDA增效剂。在某些实施方式中，该披露考虑了化合物和药物组成。在某些实施方式中，该披露考虑了本文披露的化合物作为前药，可选择性地取代一个或多个取代基，衍生物或其盐。在某些实施方式中，该披露涉及治疗或预防神经系统疾病的方法，包括向需要的受试者施用包含本文披露的化合物的有效量的组合物。
• Inhibitors of Mycobacterium Tuberculosis Malate Synthase, Methods of Making and Uses Thereof
  申请人：Freundlich Joel S.

  公开号：US20140171444A1

  公开（公告）日：2014-06-19

  The present invention provides aryl- or heteroaryl-diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl- naphthyl-, or thienyl-substituted diketo acids and carboxylate derivatives thereof. Also provided are methods of treating tuberculosis or other pathophysiological conditions associated with a malate synthase enzyme with the inhibitory compounds and methods of in silico design of the inhibitory compounds. In addition, the present invention provides the inhibitory compounds designed by this method. Furthermore, three-dimensional X-ray crystal structures of the Mycobacterial malate synthase complexed with the inhibitory compounds are provided. Further still a method for stabilizing an aromatic or heteroaromatic diketo acid or its prodrug or close analog in solution by derivatizing at least the ortho position on the aromatic ring is provided.

  本发明提供了芳基或杂环芳基二酮酸化合物，其能够有效抑制结核分枝杆菌苹果酸合酶酶活性或抑制其他具有该酶的细菌的苹果酸合酶活性。这些化合物可以是苯基、萘基或噻吩基取代的二酮酸和其羧酸衍生物。还提供了使用这些抑制剂治疗结核病或其他与苹果酸合酶酶相关的病理生理状况的方法以及通过计算机模拟设计这些抑制剂的方法。此外，本发明还提供了通过这种方法设计的抑制剂。此外，还提供了与抑制剂形成复合物的结核分枝杆菌苹果酸合酶的三维X射线晶体结构。还提供了一种通过在芳香环上至少衍生化邻位位置来稳定溶液中的芳香或杂环芳香二酮酸或其前药或类似物的方法。
• NMDA RECEPTOR MODULATORS AND USES RELATED THERETO
  申请人：EMORY UNIVERSITY

  公开号：US20150196540A1

  公开（公告）日：2015-07-16

  This disclosure relates to NMDA modulators and used related thereto such as for treatment of central nervous system disorders. In certain embodiments, compounds disclosed herein are NR2C subunit-selective NMDA potentiators. In certain embodiments, the disclosure contemplates compounds and pharmaceutical compositions. In certain embodiments, the disclosure contemplates compounds disclosed herein as prodrugs, optionally substituted with one or more substituents, derivatives, or salts thereof. In certain embodiments, the disclosure relates to methods of treating or preventing nervous system disorders comprising administering an effective amount of a composition comprising compound disclosed herein to a subject in need thereof.

  本公开涉及NMDA调节剂及其相关用途，例如用于治疗中枢神经系统疾病。在某些实施例中，本文所披露的化合物是NR2C亚单位选择性NMDA增强剂。在某些实施例中，本公开考虑化合物和制药组合物。在某些实施例中，本公开考虑化合物作为前药，可选择地用一个或多个取代基，衍生物或其盐替代。在某些实施例中，本公开涉及治疗或预防神经系统疾病的方法，包括向需要治疗的受试者施用含有本文所披露的化合物的有效量的组合物。
• Chemistry of iminofurans: IX. Synthesis and cyclization of (2Z)-2-{(2Z)-2-[2-(3-R-adamantan-1-yl)-2-oxoethylidene]hydrazinyl}-4-(het)aryl-4-oxobut-2-enoic acids
  作者：N. A. Pulina、A. S. Kuznetsov、A. E. Rubtsov

  DOI：10.1134/s1070428015070131

  日期：2015.7

  1-(3-R-adamantan-1-yl)-2-[(triphenyl-lambda(5)-phosphanylidene)hydrazinylidene]ethanone reacted with 4-aryl(hetaryl)-2,4-dioxobutanoic acids to give 2-2-[2-(3-R-adamantan-1-yl)-2-oxoethylidene]hydrazinyl}-4-aryl(hetaryl)-4-oxobut-2-enoic acids which were shown to exist in solution as mixtures of Z- and E-isomeric enehydrazine tautomers. The products underwent cyclization to 3-[2-(3-R-adamantan-1-yl)-2-oxoethylidene]- hydrazinylidene}-5-aryl(hetaryl)furan-2(3H)-ones.
• Inhibitors of mycobacterium tuberculosis malate synthase, methods of making and uses thereof
  申请人：Freundlich Joel S.

  公开号：US20100113477A1

  公开（公告）日：2010-05-06

  The present invention provides aryl- or heteroaryl-diketo acid compounds effective to inhibit an activity of a Mycobacterial malate synthase enzyme or to inhibit a malate synthase activity in other bacteria having the enzyme. The compounds may be phenyl-naphthyl-, or thienyl-substituted diketo acids and carboxylate derivatives thereof. Also provided are methods of treating tuberculosis or other pathophysiological conditions associated with a malate synthase enzyme with the inhibitory compounds and methods of in silico design of the inhibitory compounds. In addition, the present invention provides the inhibitory compounds designed by this method. Furthermore, three-dimensional X-ray crystal structures of the Mycobacterial malate synthase complexed with the inhibitory compounds are provided. Further still a method for stabilizing an aromatic or heteroaromatic diketo acid or its prodrug or close analog in solution by derivatizing at least the ortho position on the aromatic ring is provided.