1-(benzyloxy)-2-[(4-methoxyphenoxy)methyl]-4-penten-2-ol | 213828-29-6

• 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: 1-(benzyloxy)-2-[(4-methoxyphenoxy)methyl]-4-penten-2-ol
• 英文别名: 1-(4-Methoxyphenoxy)-2-(phenylmethoxymethyl)pent-4-en-2-ol
• CAS: 213828-29-6
• 化学式: C₂₀H₂₄O₄
• 分子量: 328.408
• InChiKey: ILCWAMQZPJONDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  475.2±45.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(benzyloxy)-2-[(4-methoxyphenoxy)methyl]-4-penten-2-ol 在 palladium on activated charcoal sodium periodate 、 四氧化锇 、 氢气 、 对甲苯磺酸 、 N-甲基吗啉氧化物 作用下， 以 乙酸乙酯 、 丙酮 、 甲苯 、 叔丁醇 为溶剂， 反应 25.0h， 生成 tert-butyl 4-{[(4-methoxyphenoxy)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}butanoate
  参考文献：
  名称：

  Branched Diacylglycerol-Lactones as Potent Protein Kinase C Ligands and α-Secretase Activators

  摘要：

  Using as our lead structure a potent PKC ligand (1) that we had previously described, we investigated a series of branched DAG-lactones to optimize the scaffold for PKC binding affinity and reduced lipophilicity, and we examined the potential utility of select compounds as alpha-secretase activators. Activation of alpha-secretase upon PKC stimulation by ligands causes increased degradation of the amyloid precursor protein (APP), resulting in enhanced secretion of sAPP alpha and reduced deposition of beta-amyloid peptide (A beta), which is implicated in the pathogenesis of Alzheimer's disease. We modified in a systematic manner the C-5-acyl group, the 3-alkylidene, and the lactone ring in I and established structure-activity relationships for this series of potent PKC ligands. Select DAG-lactones with high binding affinities for PKC were evaluated for their abilities to lead to increased sAPP alpha secretion as a result of alpha-secretase activation. The DAG-lactones potently induced alpha-secretase activation, and their potencies correlated with the corresponding PKC binding affinities and lipophilicities. Further investigation indicated that 2 exhibited a modestly higher level of sAPP alpha secretion than did phorbol 12,13-dibutyrate (PDBu).

  DOI：

  10.1021/jm0509391
• 作为产物：
  描述：

  2,3-环氧丙基-4-甲氧基苯基醚 在 pyridinium chloroformate 、 4 A molecular sieve 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 1-(benzyloxy)-2-[(4-methoxyphenoxy)methyl]-4-penten-2-ol
  参考文献：
  名称：

  基于四氢呋喃模板的蛋白激酶C配体，其中包含一组新的佛波酯酯药效基团。

  摘要：

  根据立体化学，一系列带有嵌入的甘油骨架的取代的四氢呋喃系列带有附加的四氢呋喃亚基乙酸盐或四氢呋喃基乙酸盐基序，分为四个不同的模板（I-IV）。根据新的修订模型，将这些化合物设计为模仿佛波酯的三个基本药效基团（C（3）-C = O，C（20）-OH和C（13）-C = O）。由缩水甘油基4-甲氧基苯基醚构成四氢呋喃环，并通过NMR光谱法（包括NOE）确定异构体模板的结构。对蛋白激酶C（PKC）的结合亲和力是根据配体从PKC的重组α同工酶置换结合的[（3）H-20] phorbol 12、13-二丁酸酯（PDBU）的能力来评估的。Z和E几何异构体（1、3，分别含有四氢呋喃亚基乙酸盐基序的）是最有效的配体，它们的K（i）值相同，为0.35 microM。对这四个模板的分子建模研究表明，当拟合到典型的佛波醇12,13-二乙酸酯时，均方根值与亲和力成反比，其相关性依次为：I约II> III> IV。

  DOI：

  10.1021/jm980713g

文献信息

• Protein Kinase C Ligands Based on Tetrahydrofuran Templates Containing a New Set of Phorbol Ester Pharmacophores
  作者：Jeewoo Lee、Ji-Hye Kang、Sang-Yoon Lee、Kee-Chung Han、Christina M. Torres、Dipak K. Bhattacharyya、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm980713g

  日期：1999.10.1

  ability of the ligands to displace bound [(3)H-20]phorbol 12, 13-dibutyrate (PDBU) from a recombinant alpha isozyme of PKC. Geometric Z- and E-isomers (1 and 3, respectively) containing a tetrahydrofuranylideneacetate motif were the most potent ligands with identical K(i) values of 0.35 microM. Molecular modeling studies of the four templates showed that the rms values when fitted to a prototypical phorbol

  根据立体化学，一系列带有嵌入的甘油骨架的取代的四氢呋喃系列带有附加的四氢呋喃亚基乙酸盐或四氢呋喃基乙酸盐基序，分为四个不同的模板（I-IV）。根据新的修订模型，将这些化合物设计为模仿佛波酯的三个基本药效基团（C（3）-C = O，C（20）-OH和C（13）-C = O）。由缩水甘油基4-甲氧基苯基醚构成四氢呋喃环，并通过NMR光谱法（包括NOE）确定异构体模板的结构。对蛋白激酶C（PKC）的结合亲和力是根据配体从PKC的重组α同工酶置换结合的[（3）H-20] phorbol 12、13-二丁酸酯（PDBU）的能力来评估的。Z和E几何异构体（1、3，分别含有四氢呋喃亚基乙酸盐基序的）是最有效的配体，它们的K（i）值相同，为0.35 microM。对这四个模板的分子建模研究表明，当拟合到典型的佛波醇12,13-二乙酸酯时，均方根值与亲和力成反比，其相关性依次为：I约II> III> IV。
• [EN] GLYCEROL COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS DE GLYCÉROL ET PROCÉDÉS D'UTILISATION
  申请人：ENZYCHEM LIFESCIENCES CORP

  公开号：WO2022058965A1

  公开（公告）日：2022-03-24

  Provided herein,inter alia, are compounds of fatty acid glycerol derivatives and compositions including the same.

  本文提供了脂肪酸甘油衍生物化合物和包含这些化合物的组合物。
• DIACYLGLYCEROL LACTONE COMPOUND, PREPARATION METHOD THEREFOR, AND IMMUNOSTIMULATOR CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：ENZYCHEM LIFESCIENCES CORPORATION

  公开号：US20210002242A1

  公开（公告）日：2021-01-07

  Disclosed are a novel diacylglycerol lactone compound for improving immunity and inhibiting infection by promoting neutrophil movement, a preparation method therefor, and an immunostimulator containing same as an active ingredient. The diacyloglycerol lactone compound is represented by chemical formula 1 of the specification. In chemical formula 1, R1 and R2 are respectively N and independently a C2-30 fatty acid group.

  本发明揭示了一种新颖的二酰甘油内酯化合物，用于通过促进中性粒细胞运动来提高免疫力和抑制感染，以及其制备方法和包含该化合物作为活性成分的免疫刺激剂。该二酰甘油内酯化合物由规范中的化学式1表示。在化学式1中，R1和R2分别为N和独立的C2-30脂肪酸基团。
• [EN] DIACYLGLYCEROL LACTONE COMPOUND, PREPARATION METHOD THEREFOR, AND IMMUNOSTIMULATOR CONTAINING SAME AS ACTIVE INGREDIENT<br/>[FR] COMPOSÉ DE DIACYLGLYCÉROL LACTONE, SON PROCÉDÉ DE FABRICATION ET IMMUNOSTIMULATEUR LE CONTENANT EN TANT QUE PRINCIPE ACTIF<br/>[KO] 디아실글리세롤락톤 화합물, 그 제조방법 및 이를 유효성분으로 함유하는 면역증진제
  申请人：ENZYCHEM LIFESCIENCES CORP

  公开号：WO2019177314A1

  公开（公告）日：2019-09-19

  호중구 이동을 촉진하여 면역을 증진시키고 감염을 억제하는 신규한 디아실글리세롤락톤 화합물, 그 제조방법 및 이를 유효성분으로 함유하는 면역증진제가 개시된다. 상기 디아실글리세롤락톤 화합물은 명세서의 화학식 1로 표시된다. 상기 화학식 1에서, R1 및 R2는 각각 독립적으로 탄소수 2 내지 30의 지방산기이다.
• Branched Diacylglycerol-Lactones as Potent Protein Kinase C Ligands and α-Secretase Activators
  作者：Jeewoo Lee、Ji-Hye Kang、Kee-Chung Han、Yerim Kim、Su Yeon Kim、Hae-Suk Youn、Inhee Mook-Jung、Hee Kim、Jee Hye Lo Han、Hee Jin Ha、Young Ho Kim、Victor E. Marquez、Nancy E. Lewin、Larry V. Pearce、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm0509391

  日期：2006.3.1

  Using as our lead structure a potent PKC ligand (1) that we had previously described, we investigated a series of branched DAG-lactones to optimize the scaffold for PKC binding affinity and reduced lipophilicity, and we examined the potential utility of select compounds as alpha-secretase activators. Activation of alpha-secretase upon PKC stimulation by ligands causes increased degradation of the amyloid precursor protein (APP), resulting in enhanced secretion of sAPP alpha and reduced deposition of beta-amyloid peptide (A beta), which is implicated in the pathogenesis of Alzheimer's disease. We modified in a systematic manner the C-5-acyl group, the 3-alkylidene, and the lactone ring in I and established structure-activity relationships for this series of potent PKC ligands. Select DAG-lactones with high binding affinities for PKC were evaluated for their abilities to lead to increased sAPP alpha secretion as a result of alpha-secretase activation. The DAG-lactones potently induced alpha-secretase activation, and their potencies correlated with the corresponding PKC binding affinities and lipophilicities. Further investigation indicated that 2 exhibited a modestly higher level of sAPP alpha secretion than did phorbol 12,13-dibutyrate (PDBu).