5-(2-chloro-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione | 1269441-48-6

• 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: 5-(2-chloro-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• CAS: 1269441-48-6
• 化学式: C₈H₉ClO₅
• 分子量: 220.609
• InChiKey: YNZIMQMOKPFTGL-UHFFFAOYSA-N

物化性质

• 沸点：
  433.7±45.0 °C(Predicted)
• 密度：
  1.430±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2-chloro-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 以 异丙醇 为溶剂， 反应 3.0h， 以27%的产率得到4-氯-3-氧代丁酸异丙酯
  参考文献：
  名称：

  [EN] 2-AMINO-1,3,4-THIADIAZINE AND 2-AMINO-1,3,4-OXADIAZINE BASED ANTIFUNGAL AGENTS
  [FR] AGENTS ANTIFONGIQUES À BASE DE 2-AMINO-1,3,4-THIADIAZINE ET DE 2-AMINO-1,3,4-OXADIAZINE

  摘要：

  该发明提供了一种化合物，其为式(I)的二氮杂环化合物或其互变异构体，或其药学上可接受的盐，用作抗真菌剂：(I)其中X、N'、C'、A和E如本文所定义。该发明还提供了一种如本文所定义的式(I)的化合物。

  公开号：

  WO2017009651A1
• 作为产物：
  描述：

  丙二酸环(亚)异丙酯 、 氯乙酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以83%的产率得到5-(2-chloro-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  K₂S₂O₈-mediated coupling of 6-amino-7-aminomethyl-thiazolino-pyridones with aldehydes to construct amyloid affecting pyrimidine-fused thiazolino-2-pyridones

  摘要：

  我们在此提出了通过K₂S₂O₈介导的氧化偶联，合成了多样化官能化的嘧啶融合噻唑-2-吡啶酮，该噻唑-2-吡啶酮与醛类发生反应。

  DOI：

  10.1039/d1ob01580j

文献信息

• Synthesis of Densely Functionalized <i>N</i>-Alkenyl 2-Pyridones via Benzyne-Induced Ring Opening of Thiazolino-Fused 2-Pyridones
  作者：Pardeep Singh、Andrew G. Cairns、Dan E. Adolfsson、Jörgen Ådén、Uwe H. Sauer、Fredrik Almqvist

  DOI：10.1021/acs.orglett.9b02549

  日期：2019.9.6

  We report the synthesis of 6-arylthio-substituted-N-alkenyl 2-pyridones by ring opening of bicyclic thiazolino-2-pyridones with arynes. Varied functionalization was used to investigate scope and substituent influences on reactivity. Selected conditions favor thioether ring opening over [4 + 2] cycloaddition and an unusual aryne incorporating ring expansion. Deuterium labeling was used to clarify observed

  我们报告了与芳烃的双环噻唑啉-2-吡啶酮的开环反应，合成了6-芳硫基取代的-N-烯基2-吡啶酮。各种功能化用于研究范围和取代基对反应性的影响。选定的条件比[4 + 2]环加成更有利于硫醚开环，并且不寻常的芳烃具有扩环功能。氘标记用于澄清观察到的反应性。利用这些知识，我们制备了具有复杂取代模式的类药物分子，并展示了硫醚开环如何可用于具有竞争反应性的支架上。
• Structure-Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of <i>Listeria monocytogenes</i>
  作者：Martina Kulén、Marie Lindgren、Sabine Hansen、Andrew G. Cairns、Christin Grundström、Afshan Begum、Ingeborg van der Lingen、Kristoffer Brännström、Michael Hall、Uwe H. Sauer、Jörgen Johansson、A. Elisabeth Sauer-Eriksson、Fredrik Almqvist

  DOI：10.1021/acs.jmedchem.8b00289

  日期：2018.5.10

  extensive hydrophobic network that restricts the protein’s ability to form functional DNA-binding helix–turn–helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-AI selective PrfA inhibitors with potent antivirulence properties.

  单核细胞增生李斯特菌是一种细菌病原体，可通过转录调节剂PrfA控制其大部分毒力。在这项研究中，我们描述了结构指导的设计和一组基于环稠合的2-吡啶酮杂环的PrfA抑制剂的合成。与以前鉴定的化合物相比，我们最有效的化合物降低了毒力因子的表达，减少了细菌对真核细胞的摄取，并提高了感染单核细胞增生李斯特菌的鸡胚的存活率。晶体结构确定蛋白内“隧道”为主要抑制剂结合位点（A I），这些化合物会参与一个广泛的疏水网络，从而限制了蛋白质形成功能性DNA结合螺旋-转-螺旋（HTH）基序的能力。我们的研究还揭示了HTH母题迄今未曾想到的结构可塑性。总之，我们设计了2-吡啶酮类似物，其具有有效的抗病毒特性，可作为位点A I选择性PrfA抑制剂。
• [EN] 2,3-DIHYDRO-THIAZOLO[3,2-A]PYRIDIN-5-ONE DERIVATIVES, INTERMEDIATES THEREOF, AND THEIR USE AS ANTIBACERIAL AGENTS<br/>[FR] DÉRIVÉS DE 2,3-DIHYDRO-THIAZOLO [3,2-A] PYRIDIN-5-ONE, LEURS INTERMÉDIAIRES ET LEUR UTILISATION COMME AGENTS ANTIBACTÉRIENS
  申请人：QURETECH BIO AB

  公开号：WO2016075296A1

  公开（公告）日：2016-05-19

  The disclosure relates to certain novel substituted ring-fused thiazolino 2- pyridones of Formula I, to processes for preparing such compounds, to their use in treating a bacterial infection such as a Chlamydia infection, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  该披露涉及某些新型取代环融合噻唑烷基吡啶酮化合物，其化学式为I，涉及制备这类化合物的过程，以及它们在治疗细菌感染，如沙眼衣原体感染中的用途，涉及它们的治疗用途方法以及含有它们的药物组合物。
• 2,3-dihydro-thiazolo[3,2-A]pyridin-5-one derivatives, intermediates thereof, and their use as antibacterial agents
  申请人：Quretech Bio AB

  公开号：US10294244B2

  公开（公告）日：2019-05-21

  The disclosure relates to certain novel substituted ring-fused thiazolino 2-pyridines of Formula I, to processes for preparing such compounds, to their use in treating a bacterial infection such as Chlamydia infection, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本公开涉及式 I 的某些新型取代环融噻唑 2-吡啶、制备此类化合物的工艺、它们在治疗衣原体感染等细菌感染中的用途、它们的治疗方法以及含有它们的药物组合物。
• Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy
  作者：Andrew G. Cairns、Ana Vazquez-Romero、Mohammad Mahdi Moein、Jörgen Ådén、Charles S. Elmore、Akihiro Takano、Ryosuke Arakawa、Andrea Varrone、Fredrik Almqvist、Magnus Schou

  DOI：10.1021/acschemneuro.8b00236

  日期：2018.11.21

  Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (alpha-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood -brain barrier permeability in nonhuman primates (NHP) in vivo. For this purpose, 2-pyridone 12 was prepared and found to accelerate alpha-syn fibrillization in vitro. Acid 12, and its acetoxymethyl ester analogue 14, were then radiolabeled with C-11 (t(1/2) = 20.4 min) at high radiochemical purity (>99%) and high specific radioactivity (>37 GBq/mu mol). Following intravenous injection of each compound in NHP, a 4-fold higher radioactivity in brain was observed for [C-11]14 compared to [C-11]12 (0.8 vs 0.2 SUV, respectively). [C-11]14 was rapidly eliminated from plasma, with [C-11]12 as the major metabolic product observed by radio-HPLC. The presented prodrug approach paves the way for future development of 2-pyridones as imaging biomarkers for in vivo imaging of alpha-synuclein deposits in brain.