diethyl ((5-((4-methoxybenzyl)oxy)-4-oxo-4H-pyran-2-yl)methyl)phosphonate | 1381864-98-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: diethyl ((5-((4-methoxybenzyl)oxy)-4-oxo-4H-pyran-2-yl)methyl)phosphonate
• 英文别名: 2-(Diethoxyphosphorylmethyl)-5-[(4-methoxyphenyl)methoxy]pyran-4-one；2-(diethoxyphosphorylmethyl)-5-[(4-methoxyphenyl)methoxy]pyran-4-one
• CAS: 1381864-98-7
• 化学式: C₁₈H₂₃O₇P
• 分子量: 382.35
• InChiKey: HXYBTKRHQUYJLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  26.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  84.2
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  diethyl ((5-((4-methoxybenzyl)oxy)-4-oxo-4H-pyran-2-yl)methyl)phosphonate 在 palladium on activated charcoal 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  磺酰哌嗪LpxH抑制剂的结构-活性关系通过LpxE偶联的孔雀石绿分析进行了分析。

  摘要：

  脂质A生物合成的Raetz途径中的UDP-2,3-二酰基葡萄糖胺焦磷酸酶LpxH是绝大多数革兰氏阴性病原体中的必需酶，并且是出色的新型抗生素靶标。32P放射自显影薄层色谱分析法已广泛用于分析LpxH活性，但在较长时间内无法评估大量LpxH抑制剂。在这里，我们报告了一种耦合的非放射性LpxH分析方法，该方法利用最近发现的Aquifex aeolicus脂质A 1-磷酸酶LpxE从脂质X（LpxH催化产物）中定量去除1-磷酸。随后通过比色孔雀石绿测定法对释放的无机磷酸盐进行定量，从而可以监测LpxH催化作用。使用这种耦合酶法，我们报告了一系列磺酰基哌嗪LpxH抑制剂的生化特性。我们的分析建立了这类化合物的初步结构-活性关系，并揭示了两个芳环，两个疏水基团和一个氢键受体的药效基团。我们希望我们的发现将有助于开发更有效的LpxH抑制剂作为潜在的抗菌剂。

  DOI：

  10.1021/acsinfecdis.8b00364
• 作为产物：
  描述：

  4-甲氧基氯苄 在 potassium carbonate 、 三乙胺 、 sodium bromide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 26.5h， 生成 diethyl ((5-((4-methoxybenzyl)oxy)-4-oxo-4H-pyran-2-yl)methyl)phosphonate
  参考文献：
  名称：

  Synthesis of kojic acid-derived copper-chelating apoptosis inducing agents

  摘要：

  Three classes of kojic acid derivatives were synthesized and examined for their antiproliferative activity against HeLa cells. Both 8b and 11 co-treated with copper ion exhibited synergistic effect on the HeLa cell growth inhibition with GI(50) values of 11.9 and 7.1 mu M, respectively. Flow cytometric analysis of HeLa cells revealed that 11-Cu co-treatment induced the sub-G1 arrest in a dose-dependent manner, suggesting that the growth-inhibitory effect is attributed to DNA fragmentation. Moreover, western blot of HeLa cells cytosolic extracts displayed the cleavage of the 116-kDa protein poly(ADP-ribose) polymerase and activation of caspase-3 by the reduced level of the 32-kDa proenzyme, indicating that the caspase-dependent apoptotic pathway was involved. We further demonstrated that MAPK pathway regulators such as ERK and p38 were activated in response to 11-Cu co-treatment, suggesting that the intracellular oxidative stress was dramatically stimulated by the copper ion. Taken together, we have successfully synthesized kojic acid-derived copper-induced apoptotic agents.

  DOI：

  10.1007/s00044-012-0094-y

文献信息

• [EN] LPXH TARGETING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME<br/>[FR] COMPOSÉS DE CIBLAGE LPXH, LEURS COMPOSITIONS ET PROCÉDÉS DE FABRICATION ET D'UTILISATION ASSOCIÉS
  申请人：UNIV DUKE

  公开号：WO2021072369A1

  公开（公告）日：2021-04-15

  LpxH targeting compounds, compositions thereof, as well as methods for for making and using the same are disclosed herein. The LpxH target compounds typically have a structure pursuant to Formula (I) and/or a salt thereof, wherein Rb is selected from a single bond, C4 to C10 unsubstituted aryl, C4 to C10 substituted aryl, unsubstituted or substituted four to ten member heterocycle ring, C1 to C10 unsubstituted alkyl, and C1 to C10 substituted alkyl; Rc comprises hydrogen, halogen, -OH, -CO2CH3, -COOH, -CN2CF3, -CF3,-C2OH, -CONHOH, -CCOH, C4 to C10 unsubstituted aryl, C4 to C10 substituted aryl, unsubstituted or substituted four to ten member heterocycle ring, C1 to C10 unsubstituted alkyl, or C1 to C10 substituted alkyl; and Rd and Re are independently hydrogen, -OH, -COH, -COH, -COC, -COOH, Rf, or are taken together as an unsubstituted or substituted four to eight member nitrogen containing heterocycle ring.

  LpxH靶向化合物，其组合物，以及制备和使用这些化合物的方法在此披露。LpxH靶向化合物通常具有符合式(I)的结构和/或其盐，其中Rb从单键，C4到C10未取代芳基，C4到C10取代芳基，未取代或取代的四到十元杂环环，C1到C10未取代烷基，和C1到C10取代烷基中选择；Rc包括氢，卤素，-OH，-CO2CH3，-COOH，-CN2 ，-CF3，-C2OH，-CONHOH，-CCOH，C4到C10未取代芳基，C4到C10取代芳基，未取代或取代的四到十元杂环环，C1到C10未取代烷基，或C1到C10取代烷基；而Rd和Re独立地是氢，-OH，-COH，-COH，-COC，-COOH，Rf，或作为未取代或取代的四到八元含氮杂环环一起取代。
• Design, synthesis and biological evaluation of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues as multiple functional agents with the potential for the treatment of Alzheimer’s disease
  作者：Chenxian Hu、Liu Jiang、Li Tang、Minkui Zhang、Rong Sheng

  DOI：10.1016/j.bmc.2021.116306

  日期：2021.8

  A novel series of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues were designed and synthesized as H3 receptor antagonism based multitarget-directed ligands (MTDLs) for AD therapy using pharmacophore-combine strategy. The 2-styryl-5-hydroxy-4-pyrone pharmacophore with metal ion chelation, antioxidation, and Aβ aggregation inhibition activities was employed as the “eastern part”, and a typical

  一系列新的 2-styryl-5-hydroxy-4-pyrone 衍生物和类似物被设计和合成为基于H 3受体拮抗作用的多靶点定向配体 (MTDLs)，用于使用药效团组合策略进行 AD 治疗。与金属离子螯合，抗氧化，和A中的2-苯乙烯基-5-羟基-4-吡喃酮药效β聚集抑制活性被用作“东部”，典型的phenoxyalkylamine部分用作“中心环+西部” H 3受体拮抗剂。生物学评估表明，大多数目标化合物表现出所需的多种功能。两种最有前途的化合物8a和8b表现出纳摩尔 IC 50对H 3受体拮抗作用的值，优异的金属离子螯合能力，比Trolox更有效的ABTS +清除活性，有效的A β自聚集和Cu 2+诱导的聚集抑制活性，以及​​对A β自身/Cu 2 的解聚活性+ -诱导聚集。