5-(2-(4-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione | 1035695-10-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(2-(4-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• 英文别名: 5-[2-(4-Fluorophenyl)-1-hydroxyethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione
• CAS: 1035695-10-3
• 化学式: C₁₄H₁₃FO₅
• 分子量: 280.253
• InChiKey: YNDHEOHBRKCHET-UHFFFAOYSA-N

物化性质

• 沸点：
  499.3±45.0 °C(Predicted)
• 密度：
  1.349±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(2-(4-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 生成 ethyl 5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

  摘要：

  Bioisosteric replacement of acylureido moiety in 6-acylureido-3-pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2-dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.

  DOI：

  10.1016/j.ejmech.2014.07.033
• 作为产物：
  描述：

  丙二酸环(亚)异丙酯 、 4-氟苯乙酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 5-(2-(4-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  脂氧唑烷酮抗生素的扩展结构-活性研究

  摘要：

  已发现含有不常见的4-恶唑烷酮核心的海洋天然产物lipoxazolidinone系列具有对耐甲氧西林的金黄色葡萄球菌（MRSA）的有效抗菌活性。在本文中，我们通过制备脂环唑烷酮的选定芳基衍生物并进一步评估将此类分子的活性扩展至革兰氏阴性病原体的潜力，扩大了我们先前的合成努力。使用这些类似物，我们探索了改变芳环周围的取代方式，增加恶唑烷酮核心与芳基系统之间的链长以及改变极性更大的官能团的位置如何影响抗菌活性的影响。最后，我们利用了大肠杆菌的TolC基因敲除菌株证明我们的化合物在革兰氏阴性病原体中外排，并且这些敲除物中的活性得以恢复。这些结果一起提供的4-恶唑烷酮类似物的进一步发展的附加数据5，20，和21用于传染病的治疗。

  DOI：

  10.1021/acsmedchemlett.9b00015

文献信息

• Enantioselective Carbene Cascade: An Effective Approach to Cyclopentadienes and Applications in Diels-Alder Reactions
  作者：Xiangbo Wang、Yunfei Zhou、Lihua Qiu、Ruwei Yao、Yang Zheng、Cheng Zhang、Xiaoguang Bao、Xinfang Xu

  DOI：10.1002/adsc.201501106

  日期：2016.5.19

  An asymmetric carbene cascade reaction, which proceeds through carbene/alkyne metathesis and formal (3+2) cycloaddition and converts alkynyl‐tethered enol diazoacetates to chiral bicyclic cyclopentadienes, is presented; and no catalytic asymmetric version of these carbene cascade transformations has been disclosed so far. The proton signals of the cyclopropene intermediates are observed in the mechanism

  提出了一种不对称卡宾级联反应，该反应通过卡宾/炔烃复分解和形式（3 + 2）环加成反应进行，并将炔基连接的烯醇重氮乙酸酯转化为手性双环环戊二烯。并且迄今尚未公开这些卡宾级联转化的催化不对称形式。在机理研究中观察到了环丙烯中间体的质子信号，清楚地表明了反应途径。此外，这些产物通过Diels-Alder反应被拦截，从而以高收率和对映选择性提供桥连的多环结构。
• Synthesis and Characterization of a Multi Ring-Fused 2-Pyridone-Based Fluorescent Scaffold
  作者：Magnus Sellstedt、Anders Nyberg、Erik Rosenbaum、Patrik Engström、Malin Wickström、Joachim Gullbo、Sven Bergström、Lennart B.-Å. Johansson、Fredrik Almqvist

  DOI：10.1002/ejoc.201000796

  日期：2010.11

  A series of compounds based on a novel fluorescent scaffold have been synthesized. Most of the compounds displayed high quantum yields of fluorescence and unusually long fluorescence lifetimes. HeLa cells were treated with one of the compounds and its use as a fluorescent dye was demonstrated with fluorescence confocal microscopy.

  已经合成了一系列基于新型荧光支架的化合物。大多数化合物显示出高荧光量子产率和异常长的荧光寿命。HeLa 细胞用其中一种化合物处理，荧光共聚焦显微镜证明了其作为荧光染料的用途。
• Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity
  作者：Osvaldo Gutierrez、Dattatray Metil、Namrata Dwivedi、Nagaraju Gudimalla、E. R. R. Chandrashekar、Vilas H. Dahanukar、Apurba Bhattacharya、Rakeshwar Bandichhor、Marisa C. Kozlowski

  DOI：10.1021/acs.orglett.5b00520

  日期：2015.4.3

  The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H center dot center dot center dot F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.
• Discovery of Pyrrolopyridine−Pyridone Based Inhibitors of Met Kinase: Synthesis, X-ray Crystallographic Analysis, and Biological Activities
  作者：Kyoung Soon Kim、Liping Zhang、Robert Schmidt、Zhen-Wei Cai、Donna Wei、David K. Williams、Louis J. Lombardo、George L. Trainor、Dianlin Xie、Yaquan Zhang、Yongmi An、John S. Sack、John S. Tokarski、Celia Darienzo、Amrita Kamath、Punit Marathe、Yueping Zhang、Jonathan Lippy、Robert Jeyaseelan、Barri Wautlet、Benjamin Henley、Johnni Gullo-Brown、Veeraswamy Manne、John T. Hunt、Joseph Fargnoli、Robert M. Borzilleri

  DOI：10.1021/jm800476q

  日期：2008.9.11

  Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC(50) value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors Such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent anti proliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC(50) values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTI-16 human gastric carcinoma xenograft model.