5-(2-(2-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione | 1621689-64-2

• 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-(2-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
• CAS: 1621689-64-2
• 化学式: C₁₄H₁₃FO₅
• 分子量: 280.253
• InChiKey: SSDGYAWJVDFLHE-UHFFFAOYSA-N

物化性质

• 沸点：
  494.5±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)：
  2.02
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.83
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-(2-(2-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-(2-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 、 邻氟苯乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 5-(2-(2-fluorophenyl)-1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione
  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

文献信息

• Design of β-Keto Esters with Antibacterial Activity: Synthesis, In Vitro Evaluation, and Theoretical Assessment of Their Reactivity and Quorum-Sensing Inhibition Capacity
  作者：Maximiliano Martínez-Cifuentes、Emmanuel Soto-Tapia、Camila Linares-Pipón、Ben Bradshaw、Paulina Valenzuela-Hormazabal、David Ramírez、Patricio Muñoz-Torres、Claudio Parra

  DOI：10.3390/ph16101339

  日期：——

  proposes the design of β-keto esters as antibacterial compounds. The design was based on the structure of the autoinducer of bacterial quorum sensing, N-(3-oxo-hexanoyl)-l-homoserine lactone (3-oxo-C6-HSL). Eight β-keto ester analogues were synthesised with good yields and were spectroscopically characterised, showing that the compounds were only present in their β-keto ester tautomer form. We carried out

  这项工作提出了将 β-酮酯设计为抗菌化合物。该设计基于细菌群体感应的自诱导剂 N-(3-氧代-己酰基)-l-高丝氨酸内酯 (3-oxo-C6-HSL) 的结构。八种 β-酮酯类似物的合成具有良好的收率，并进行了光谱表征，表明这些化合物仅以 β-酮酯互变异构体形式存在。我们对化合物的反应性和 ADME（吸收、分布、代谢和排泄）特性进行了计算分析，并与 LasR 和 LuxS 群体感应（QS）蛋白进行了分子对接和分子动力学计算，其中涉及细菌对抗生素的耐药性。结果表明，所有化合物均表现出可靠的 ADME 性质，并且只有化合物 7 具有亲电子毒性。理论反应性研究表明，化合物 6 和 8 与该系列的其余化合物相比呈现出不同的局部反应性。根据其分子对接和分子动力学计算，化合物 8 在与 LasR 和 LuxS QS 蛋白有效相互作用的能力方面表现出最有前途的潜力。针对人类致病菌铜绿假单胞菌和金黄色葡萄
• 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.