diethyl [4-(benzyloxy)benzyl]malonate | 84184-50-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: diethyl [4-(benzyloxy)benzyl]malonate
• 英文别名: diethyl p-benzyloxybenzylmalonate；diethyl 2-(4-benzyloxybenzyl)malonate；[p-(benzyloxy)benzyl] malonic acid, diethyl ester；3-[4-benzyloxy-phenyl]-2-ethoxycarbonyl-propionic acid ethyl ester；Diethyl {[4-(benzyloxy)phenyl]methyl}propanedioate；diethyl 2-[(4-phenylmethoxyphenyl)methyl]propanedioate
• CAS: 84184-50-9
• 化学式: C₂₁H₂₄O₅
• 分子量: 356.419
• InChiKey: DHIVGDFXQKJDMK-UHFFFAOYSA-N

物化性质

• 沸点：
  465.6±35.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  diethyl [4-(benzyloxy)benzyl]malonate 在 nitrosopotassium 作用下， 以 乙醇 、 水 为溶剂， 150.0~160.0 ℃ 、2.67 kPa 条件下， 反应 3.0h， 生成 3-[4-(苄氧基)苯基]丙酸
  参考文献：
  名称：

  Ishii, Hisashi; Ishikawa, Tsutomu; Tohojoh, Toshiaki, Journal of the Chemical Society. Perkin transactions I, 1982, # 9, p. 2051 - 2058

  摘要：

  DOI：
• 作为产物：
  描述：

  对羟基苯甲醇 在 氯化亚砜 、 sodium hydride 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 10.5h， 生成 diethyl [4-(benzyloxy)benzyl]malonate
  参考文献：
  名称：

  2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands

  摘要：

  A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-alpha ligands. Among the analogues, 13c exhibited the most potent binding affinity with a K-i = 0.7 mu M. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study or 13c was carried out. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.051

文献信息

• Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate
  作者：Eloi P Coutant、Vincent Hervin、Glwadys Gagnot、Candice Ford、Racha Baatallah、Yves L Janin

  DOI：10.3762/bjoc.14.264

  日期：——

  We have explored here the scope of the age-old diethyl malonate-based accesses to α-amino esters involving Knoevenagel condensations of diethyl malonate on aldehydes, reductions of the resulting alkylidenemalonates, the preparation of the corresponding α-hydroxyimino esters and their final reduction. This synthetic pathway turned out to be general although some unexpected limitations were encountered

  我们在这里探索了基于古老的丙二酸二乙酯对α-氨基酯的接触范围，该方法涉及丙二酸二乙酯在醛上的Knoevenagel缩合反应，所得亚烷基丙二酸酯的还原，相应α-羟基亚氨基酯的制备及其最终还原。尽管遇到了一些意想不到的限制，但这种合成途径被证明是通用的。在进行肟化步骤之前，使用Suzuki-Miyaura偶联或环加成法对某些中间体进行了合成修饰，从而获得了更多的α-氨基酯。此外，探索了其他通往α-羟基亚氨基酯的途径，包括试图改善乙基β-溴-α-羟基亚氨基羧酸酯与各种烷基呋喃化合物之间的环加成反应。
• Aminobenzoic and aminocyclohexane-carboylic acid compounds, compositions, and their method of use
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0361365A1

  公开（公告）日：1990-04-04

  Compounds of the formula wherein X is inhibit the action of neutral endopeptidase. As a result, such compounds produce diuresis, natriuresis, and lower blood pressure as well as being useful in the treatment of congestive heart failure, relieving pain, and diarrhea when administered to a mammalian host.

  其中X的化合物抑制中性内肽酶的作用。因此，这些化合物产生利尿、排钠和降低血压的效果，同时在治疗充血性心力衰竭、缓解疼痛和腹泻时对哺乳动物宿主有用。
• Design and synthesis of novel oxazole containing 1,3-Dioxane-2-carboxylic acid derivatives as PPAR α/γ dual agonists
  作者：Harikishore Pingali、Mukul Jain、Shailesh Shah、Pankaj Makadia、Pandurang Zaware、Ashish Goel、Megha Patel、Suresh Giri、Harilal Patel、Pankaj Patel

  DOI：10.1016/j.bmc.2008.06.050

  日期：2008.8

  A few novel 1,3-dioxane carboxylic acid derivatives were designed and synthesized to aid in the characterization of PPAR alpha/gamma dual agonists. Structural requirements for PPARalpha/gamma dual agonism of 1,3-dioxane carboxylic acid derivatives included the structural similarity with potent glitazones in fibric acid chemotype. The compounds with this pharmacophore and substituted oxazole as a lipophilic

  设计和合成了一些新颖的1,3-二恶烷羧酸衍生物，以帮助表征PPARα/γ双激动剂。1,3-二恶烷羧酸衍生物的PPARalpha /γ双激动性的结构要求包括与强酸格列酮在纤维酸化学型中的结构相似性。合成了具有该药效团和取代的恶唑作为亲脂性杂环尾巴的化合物，并在动物模型中评估了其体外PPAR激动剂的潜力以及体内降血糖和降血脂的功效。铅化合物2-甲基-c-5- [4-（5-（甲基-2-（4-甲基苯基）-恶唑-4-基甲氧基）-苄基] -1,3-二恶烷-r-2-羧酸13b在db / db小鼠和Zucker fa / fa大鼠中表现出有效的降血糖，降血脂和胰岛素增敏作用。
• Malonic acid derivatives and methods for their synthesis
  申请人：Eniricerche S.p.A.

  公开号：US04914226A1

  公开（公告）日：1990-04-03

  The present invention refers to a new class of malonic acid derivatives of general formula I ##STR1## wherein R.sup.1 and R.sup.2, each independently, represent hydrogen or a carboxyl protecting group, and the residue R corresponds to the side-chain of the amino acids lysine, ornithine, tyrosine, cysteine, asparatic acid and glutamic acid wherein the additional functionalities are suitably protected. The new compounds of the present invention are useful for preparing analogues of biologically active peptides wherein the direction of some amide bonds in which the amino acids lysine, ornithine, tyrosine, cysteine, aspartic acid or glutamic acid are involved, has been reversed.

  本发明涉及一种新的马来酸衍生物类别，其通式为I，其中R.sup.1和R.sup.2分别独立地表示氢或羧基保护基，残基R对应于氨基酸赖氨酸、鸟氨酸、酪氨酸、半胱氨酸、天冬氨酸和谷氨酸的侧链，其中额外的官能团适当地被保护。本发明的新化合物可用于制备生物活性肽的类似物，其中某些酰胺键的方向，这些酰胺键涉及氨基酸赖氨酸、鸟氨酸、酪氨酸、半胱氨酸、天冬氨酸或谷氨酸，已被颠倒。
• Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists
  作者：Harikishore Pingali、Mukul Jain、Shailesh Shah、Pankaj Makadia、Pandurang Zaware、Jeevankumar Jamili、Kalapatapu V.V.M. Sairam、Pravin Patil、Dinesh Suthar、Suresh Giri、Harilal Patel、Pankaj Patel

  DOI：10.2174/157018010791306533

  日期：2010.7.1

  1,3-dioxane carboxylic acid derivatives were prepared based on our previous studies directed towards identifying novel pharmacophore for the development of PPAR α/γ dual agonists. Based on the typical topology of PPAR agonists we focused our design approach on modifying lipophilic tail and prepared a series of compounds by replacing the oxazole moiety of our previously reported compound with optimized lipophilic groups. Compound 8a was found to be a weak PPAR activator but exhibited potent hypolipidemic and anti-hyperglycemic activities in vivo due to superior bioavailability, whereas 8f exhibited potent in vitro and invivo effects. The activity of 8f is further supported by molecular docking study.

  1,3- 二氧六环羧酸衍生物的制备基于我们之前的研究，这些研究旨在为 PPAR α/γ 双激动剂的开发确定新的药理基础。根据 PPAR 激动剂的典型拓扑结构，我们将设计方法的重点放在了亲脂性尾部的修饰上，并用优化的亲脂基团取代了之前报道的化合物中的噁唑分子，制备了一系列化合物。研究发现，化合物 8a 是一种弱 PPAR 激活剂，但由于其生物利用度较高，在体内表现出了强效的降血脂和降血糖活性，而 8f 则在体外和体内都表现出了强效作用。分子对接研究进一步证实了 8f 的活性。