methyl 3-(3-benzyloxyphenyl)propenoate | 495399-41-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl 3-(3-benzyloxyphenyl)propenoate
• 英文别名: Methyl 3-(3-phenylmethoxyphenyl)prop-2-enoate；methyl 3-(3-phenylmethoxyphenyl)prop-2-enoate
• CAS: 495399-41-2
• 化学式: C₁₇H₁₆O₃
• 分子量: 268.312
• InChiKey: PCSHKRGCPKDAAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-benzyloxyphenyl)propenoate 在 palladium on activated charcoal 、 platinum on activated charcoal lithium hydroxide 、 2,4,6-三异丙基苯磺酰叠氮化物 、 甲基溴化镁 、 氢气 、 三甲基乙酰氯 、 双(三甲基硅烷基)氨基钾 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 methyl (S)-2-amino-3-(3-hydroxyphenyl)propanoate
  参考文献：
  名称：

  Development of tripeptidyl farnesyltransferase inhibitors

  摘要：

  The first example of tripeptide inhibitors of farnesyltransferase with sub-micromolar inhibition activity was developed based on the fact that CVFM is not a substrate for farnesyltransferase. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00227-5
• 作为产物：
  描述：

  间-香豆酸 在 氯化亚砜 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 methyl 3-(3-benzyloxyphenyl)propenoate
  参考文献：
  名称：

  含有修饰的A环和Seco-B环作为刺猬蛋白通路抑制剂的维生素D3类似物

  摘要：

  刺猬（Hh）信号传导途径是一种发育信号传导途径，已被认为是多种人类恶性肿瘤中抗癌药物开发的靶标。几个天然和合成的维生素基于d-开环-steroids已被鉴定为与化学治疗潜在的Hh信号传导的有效抑制剂。其中包括先前表征的类似物4，其中包含维生素D3（VD3）的北部CD环/侧链区域，该区域通过酯键与芳香族A环模拟物相连。为了进一步探讨此类基于VD3的Hh途径抑制剂的结构活性关系，我们设计，合成和评估了一系列修饰酯连接基的长度，组成和立体化学方向的化合物。这些研究确定了含有胺连接基和掺入对苯酚的芳香族A环的化合物54和55，它们是对Hh途径具有增强效力的新的先导化合物（IC 50值分别为0.40和0.32μM）。

  DOI：

  10.1016/j.ejmech.2015.01.049

文献信息

• Synthesis and Biological Activity of New 3-Hydroxy-3-methylglutaryl-CoA Synthase Inhibitors: 2-Oxetanones with a meta-Substituent on the Benzene Ring in the Side Chain.
  作者：Hirokazu HASHIZUME、Hajime ITO、Naoaki KANAYA、Hajime NAGASHIMA、Hiroyuki USUI、Reiko OSHIMA、Munefumi KANAO、Hiroshi TOMODA、Toshiaki SUNAZUKA、Hidetoshi KUMAGAI、Satoshi OMURA

  DOI：10.1248/cpb.42.1272

  日期：——

  Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activivies towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphanyl)ethyl]-3-hydroxymethyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.

  同位素侧链类似物3a被合成并测试了对3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶以及在Hep G2细胞和小鼠肝脏中胆固醇生成的抑制活性。结果表明，芳环上的亲脂性取代基和侧链末端的亲水性基团对活性的增强非常重要。4-[2-(3-正己氧基苯基)乙基]-3-羟甲基-2-氧杂环丁酮（5a）在体内的抑制活性与1233A相当。
• Synthesis and Biological Activity of New 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Synthase Inhibitors: 2-Oxetanones with a Side Chain Mimicking the Folded Structure of 1233A.
  作者：Hirokazu HASHIZUME、Hajime ITO、Kohji YAMADA、Hajime NAGASHIMA、Munefumi KANAO、Hiroshi TOMODA、Toshiaki SUNAZUKA、Hidetoshi KUMAGAI、Satoshi OMURA

  DOI：10.1248/cpb.42.512

  日期：——

  To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxetanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.

  为模拟1233A（1）的折叠侧链构象，该化合物是一种3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）合酶抑制剂，合成了侧链含有芳环的1233A类似物。其中2-恶坦酮部分保持不变。在1233A及其合成类似物中，反式-3-羟甲基-4-[2-(7-甲氧羰基-1-萘基)乙基]-2-恶坦酮（23）显示了最高的HMG-CoA合酶体外抑制活性。讨论了侧链上的构效关系。
• Synthesis of novel 1-phenyl-benzopyrrolizidin-3-one derivatives and evaluation of their cytoneuroprotective effects against NMDA-induced injury in PC12 cells
  作者：Lishou Yang、Qian Yang、Enhua Wang、Juan Yang、Qiji Li、Jiafu Cao、Li Wang、Xiu Liao、Yan Yang、Xiaosheng Yang

  DOI：10.1016/j.bmc.2022.116675

  日期：2022.4

  n-3-one derivatives were synthesized and evaluated for neuroprotective effects against N-methyl-ᴅ-aspartate (NMDA)-induced injury in PC12 cells. Interestingly, derivatives that 1-phenyl moiety bearing electron-donating group, especially benzyloxy, and the trans-forms exhibited better protective activity against NMDA-induced neurotoxicity. Compound 11 m demonstrated the best neuroprotective potency

  合成了一系列新型 1-苯基-苯并吡咯烷-3-one 衍生物，并评估了其对N-甲基-ᴅ-天冬氨酸 (NMDA) 诱导的 PC12 细胞损伤的神经保护作用。有趣的是，带有给电子基团的 1-苯基部分的衍生物，尤其是苄氧基，以及反式形式对 NMDA 诱导的神经毒性表现出更好的保护活性。化合物11 m表现出最佳的神经保护效力并显示出剂量依赖性预防。在化合物11 m的情况下，由 NMDA 在 PC12 细胞中引起的细胞内钙 (Ca 2+ ) 流入增加被逆转15 μM 预处理。这些结果表明，合成的 1-苯基-苯并吡咯烷-3-酮衍生物对 NMDA 诱导的 PC12 细胞中与抑制 Ca 2+过载相关的兴奋性毒性具有神经保护作用，并且可以进一步优化用于神经保护剂的开发。
• Design, synthesis and evaluation of novel 1-phenyl-pyrrolo[1,2-b]isoquinolin-3-one derivatives as antagonists for the glycine binding site of the NMDA receptor
  作者：Lishou Yang、Huadan Liu、Enhua Wang、Huanhuan Liu、Hongshi Liu、Lang Zhou、Tingfei Deng、Xiong Pan、Zhanxing Hu、Xiaosheng Yang

  DOI：10.1016/j.ejmech.2023.115624

  日期：2023.10

  A new series of 1-phenyl-pyrrolo[1,2-b]isoquinolin-3-one derivatives were designed, synthesized and demonstrated to act as antagonists for the glycine binding site of the NMDA receptor. These new derivatives protected PC12 cells against NMDA-induced injury and cell apoptosis in vitro, among which compound 13b exhibited excellent cytoneuroprotective potency and shown a dose-dependent prevention. The

  设计、合成了一系列新的 1-苯基-吡咯并[1,2- b ]异喹啉-3-酮衍生物，并证明其可作为 NMDA 受体甘氨酸结合位点的拮抗剂。这些新衍生物在体外保护PC12细胞免受NMDA诱导的损伤和细胞凋亡，其中化合物13b表现出优异的细胞神经保护效力，并表现出剂量依赖性预防作用。当用化合物13b预处理时，PC12细胞中由NMDA引起的细胞内Ca 2+流入增加被逆转。此外，化合物13b与 NMDA 受体甘氨酸结合位点之间的相互作用通过MST测定进行了验证。观察到化合物13b的立体化学不影响结合亲和力，这与神经保护结果一致。分子对接研究通过化合物 13b 与甘氨酸结合袋中关键氨基酸的 Pi 堆积、阳离子 Pi、H 键合和 Pi 电子相互作用证实了所观察到的活性。这些结果证实了 1-苯基-吡咯并[1,2- b ]异喹啉-3-酮衍生物作为针对 NMDA 受体甘氨酸结合位点的神经保护剂的潜力。
• Polymer-Assisted Solution-Phase Synthesis Under Combined Ultrasound and Microwave Irradiation: Preparation of <font>α</font>,<font>β</font>-Unsaturated Esters and Carboxylic Acids, Key Intermediates of Novel Sigma Ligands
  作者：D. Rossi、M. Urbano、A. Carnevale Baraglia、M. Serra、F. Bergamelli、M. Iannelli、O. Azzolina、S. Collina

  DOI：10.1080/00397910902738112

  日期：2009.8.20

  The optimal conditions to prepare ,-unsaturated methyl esters via Wittig reaction combining polymer-assisted solution-phase synthesis (PASPS) methodology and simultaneous ultrasound and microwave irradiation were established. The effects of temperature, solvent, and irradiation time were discussed. Results clearly indicated the superiority of combined ultrasound and microwave-assisted procedure over microwave-assisted methodology. Moreover, an efficient PASPS procedure to prepare ,-unsaturated carboxylic acids via tandem Wittig olefination and hydrolysis reaction was developed under combined ultrasound and microwave irradiation. Generally, a good conversion of aldehydes to acids was observed. The optimized protocols allowed us to quickly prepare a small collection of either ,-unsaturated esters or carboxylic acids, key intermediates for the drug-discovery process of new sigma ligands.