3,4-dimethoxybenzyl 3-oxobutanoate | 53779-69-4

• 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: 3,4-dimethoxybenzyl 3-oxobutanoate
• 英文别名: (3,4-Dimethoxyphenyl)methyl 3-oxobutanoate
• CAS: 53779-69-4
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: GRNUWNYJUHOVPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,4-dimethoxybenzyl 3-oxobutanoate 在 4-乙酰氨基苯磺酰叠氮 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 3,4-dimethoxybenzyl 3-[(tert-butyldimethylsilyl)oxy]-2-diazobut-3-enoate
  参考文献：
  名称：

  通过分子内环丙烷/布氏反应/应对重排的级联直接进入[3.2.2]壬三烯结构框架

  摘要：

  一锅法级联的烯醇二氮杂苄酯，是由二价（II）催化的分子内环丙烯形成引发的，它是通过随后的布赫纳反应和Cope重排发生的，以高产率和高选择性直接获得双环[3.2.2]壬三烯衍生物。

  DOI：

  10.1021/ol503498n
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 3,4-二甲氧基苄醇 在 silver trifluoromethanesulfonate 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以90%的产率得到3,4-dimethoxybenzyl 3-oxobutanoate
  参考文献：
  名称：

  AgOTf-catalyzed transesterification of β-keto esters

  摘要：

  AgOTf proved to be an effective catalyst for the transesterification of β‐keto esters with primary, secondary and tertiary alcohols. The products were obtained in high yield within a reasonable reaction time period. The kinetics of the transesterification reaction were also studied and the reaction was found to follow second‐order kinetics. Copyright © 2012 John Wiley & Sons, Ltd.

  DOI：

  10.1002/aoc.2826

文献信息

• Synthesis, evaluation and absolute configuration assignment of novel dihydropyrimidin-2-ones as picomolar sodium iodide symporter inhibitors
  作者：Pierre Lacotte、David-Alexandre Buisson、Yves Ambroise

  DOI：10.1016/j.ejmech.2013.01.043

  日期：2013.4

  A small library of dihydropyrimidin-2-ones (DHPMs) was synthesized and evaluated for their potency to block iodide entrapment in rat thyroid cells. Synthesis was achieved using the multicomponent Biginelli reaction. Twelve compounds were tested for the inhibition of sodium iodide symporter (NIS) in a cell-based assay. One newly synthesized derivative exhibited a remarkably strong activity, with a half-maximum

  合成了一个小分子二氢嘧啶-2-酮（DHPM）库，并评估了它们在大鼠甲状腺细胞中阻断碘化物截留的能力。使用多组分Biginelli反应可实现合成。在基于细胞的分析中测试了十二种化合物对碘化钠同向转运蛋白（NIS）的抑制作用。一种新合成的衍生物表现出非常强的活性，抑制浓度值达到一半（IC 50）65 pM。使用手性HPLC从外消旋物进一步拆分出三个DHPM，并使用圆二色谱法确定了绝对构型。生物学评估表明，大多数针对NIS的活性都存在于一种对映异构体中。这项研究为抗甲状腺药物的开发以及旨在研究细胞和分子水平上碘化物转运机制的新型药理学工具的合成提供了新见识。
• 1,4‐Dihydropyridinebutyrolactone‐derived ring‐opened ester and amide analogs targeting BET bromodomains
  作者：Jiewei Jiang、Pei‐Liang Zhao、Logan H. Sigua、Alice Chan、Ernst Schönbrunn、Jun Qi、Gunda I. Georg

  DOI：10.1002/ardp.202200288

  日期：2022.11

  showed that neither the affinity nor the selectivity of the ester and lactam analogs was improved for BRD4-1 and the first bromodomain of the testis-specific bromodomain (BRDT-1). The esters retained affinity comparable to the parent compound, whereas the affinity for the amide analogs was reduced 10-fold. A representative benzyl ester analog was found to retain high selectivity for BET bromodomains

  基于先前报道的 1,4-二氢吡啶丁内酯虚拟筛选结果，制备了九种内酯开环酯和七种酰胺类似物。这些类似物旨在提供与睾丸特异性溴结构域 (ZA) 通道 ZA 环入口处的残基的相互作用，以增强对溴结构域和溴结构域额外末端 (BET) 亚家族的亲和力和选择性。 AlphaScreen 进行的化合物测试表明，对于 BRD4-1 和睾丸特异性溴结构域 (BRDT-1) 的第一个溴结构域，酯和内酰胺类似物的亲和力和选择性均未得到改善。酯类保留了与母体化合物相当的亲和力，而对酰胺类似物的亲和力却降低了 10 倍。 BROMOscan 表明，一种代表性的苄基酯类似物对 BET 溴结构域保持了高选择性。对与 BRD4-1 和 BRDT-1 复合的烯丙酯类似物的 X 射线分析表明，酯侧链位于 ZA 环附近并且暴露于溶剂。
• 18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction
  作者：Xia Liu、Feng Li、Xing Wen、Jiamei Zheng、Weimin Pan、Zijing Li

  DOI：10.1016/j.bmcl.2024.129818

  日期：2024.9

  Despite the availability of various C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative

  尽管有各种 C 标记的正电子发射断层扫描 (PET) 示踪剂可用于评估 P-糖蛋白 (P-gp) 功能，但仍然存在与复杂代谢、高亲脂性和低基线摄取相关的局限性。本研究旨在通过探索一系列具有增强稳定性和降低亲脂性的定制二氢吡啶 (DHP) 作为 P-gp 功能障碍的替代 PET 示踪剂来解决这些问题。与维拉帕米和其他 DHP 相比，4-(4-氟苯基)-2,6-二甲基-1,4-二氢吡啶-3,5-二羧酸二甲酯 () 在人胃癌细胞系 SGC7901 和它的耐药对应物。 [F] 使用新型“hot-Hantzsch”方法成功合成，放射化学产率为 22.1 ± 0.1%。 MicroPET/CT 成像表明，与对照组相比，P-gp 阻断小鼠大脑中 [F] 的摄取增加了 3 倍以上。此外，[F] 显示出良好的亲脂性 (log = 2.3) 和出色的清除特性，使其成为具有低背景噪声和高对比度的有前途的示踪剂候选物。
• Identification of New Nonsteroidal RORα Ligands; Related Structure–Activity Relationships and Docking Studies
  作者：Mathieu Dubernet、Nicolas Duguet、Lionel Colliandre、Christophe Berini、Stéphane Helleboid、Marilyne Bourotte、Matthieu Daillet、Lucie Maingot、Sébastien Daix、Jean-François Delhomel、Luc Morin-Allory、Sylvain Routier、Robert Walczak

  DOI：10.1021/ml300471d

  日期：2013.6.13

  A high throughput screen was developed to identify novel, nonsteroidal ROR alpha agonists. Among the validated hit compounds, the 4-(-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the ROR alpha docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex ROR alpha physiopathology.
• US4044141A
  申请人：——

  公开号：US4044141A

  公开（公告）日：1977-08-23