methyl (E)-3-(4-(4-bromobutoxy)-3-methoxyphenyl)acrylate | 1374414-07-9

• 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 (E)-3-(4-(4-bromobutoxy)-3-methoxyphenyl)acrylate
• 英文别名: methyl (E)-3-[4-(4-bromobutoxy)-3-methoxyphenyl]prop-2-enoate
• CAS: 1374414-07-9
• 化学式: C₁₅H₁₉BrO₄
• 分子量: 343.217
• InChiKey: VWEWZEYMQDJWPQ-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  20.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(4-(4-bromobutoxy)-3-methoxyphenyl)acrylate 在 silver nitrate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 生成 (E)-3-(3-methoxy-4-{[4-(nitrooxy)butyl]oxy}phenyl)acrylic acid
  参考文献：
  名称：

  Design and synthesis of rosiglitazone-ferulic acid-nitric oxide donor trihybrids for improving glucose tolerance

  摘要：

  Glucose intolerance is associated with metabolic syndrome and type 2 diabetes mellitus (T2DM) while some new therapeutic drugs, such as rosiglitazone (Rosi), for T2DM can cause severe cardiovascular side effects. Herein we report the synthesis of Rosi-ferulic acid (FA)-nitric oxide (NO) donor trihybrids to improve glucose tolerance and minimize the side effects. In comparison with Rosi, the most active compound 21 exhibited better effects on improving glucose tolerance, which was associated with its NO production, antioxidant and anti-inflammatory activities. Furthermore, 21 displayed relatively high stability in the simulated gastrointestinal environments and human liver microsomes, and released Rosi in plasma. More importantly, 21, unlike Rosi, had little stimulatory effect on the membrane translocation of aquaporin-2 (AQP2) in kidney collecting duct epithelial cells. These, together with a better safety profile, suggest that the trihybrids, like 21, may be promising candidates for intervention of glucose intolerance-related metabolic syndrome and T2DM. (C) 2018 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2018.10.006
• 作为产物：
  描述：

  阿魏酸 在 氯化亚砜 、 potassium carbonate 作用下， 反应 9.0h， 生成 methyl (E)-3-(4-(4-bromobutoxy)-3-methoxyphenyl)acrylate
  参考文献：
  名称：

  β-咔啉/羟基肉桂酸杂化物的异羟肟酸衍生物通过PI3K / Akt / mTOR途径诱导细胞凋亡和自噬。

  摘要：

  已知天然存在的β-咔啉具有抗肿瘤活性，但效果有限。为了提高其功效，开发了一系列新的通过羟基肉桂酸分子（12a-f）连接的含异羟肟酸的β-咔啉，以合并组蛋白脱乙酰基酶（HDAC）抑制作用，以获得可能的协同作用。当在体外测定中评估时，大多数类似物显示出对四种人类癌细胞的显着抗肿瘤活性。特别地，12b显示了该系列中最高的细胞毒性潜能，包括耐药性Bel7402细胞，但对正常肝LO2细胞的影响却很小。这些化合物还显示出对HDAC1 / 6的优异抑制作用，这似乎对其抗增殖特性有很大贡献。与FDA批准的HDAC抑制剂SAHA相比，化合物12b通过调节凋亡蛋白Bax，Bcl-2和caspase 3的表达，增强了组蛋白H3和α-微管蛋白的乙酰化水平，并诱导了更大的癌细胞凋亡。重要的是，12b还诱导了明显的凋亡。增加Beclin-1和LC3-II蛋白的表达并降低LC3-I和p62的表达，从而提高Bel7402

  DOI：

  10.1021/acs.jnatprod.8b00843

文献信息

• Design, Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease
  作者：Yingbo Fu、Yu Mu、Hui Lei、Pu Wang、Xin Li、Qiao Leng、Li Han、Xiaodan Qu、Zhanyou Wang、Xueshi Huang

  DOI：10.3390/molecules21101338

  日期：——

  Five novel tacrine-ferulic acid hybrid compounds (8a–e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu2+ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity

  合成了五种新型他克林-阿魏酸杂化化合物（8a-e），并在详细光谱分析的基础上鉴定了它们的结构。在体外评估了抑制乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE)、减少自诱导 β-淀粉样蛋白 (Aβ) 聚集和螯合 Cu2+ 的活性。其中，8c 和 8d 在抑制 AChE 方面表现出比 BuChE 更高的选择性。此外，8d 还显示出对自身 Aβ 聚集、螯合 Cu2+ 的活性和对 Neuro-2A 细胞中 Aβ 诱导的神经毒性的活性的显着抑制。
• Tacrine–Ferulic Acid–Nitric Oxide (NO) Donor Trihybrids as Potent, Multifunctional Acetyl- and Butyrylcholinesterase Inhibitors
  作者：Yao Chen、Jianfei Sun、Lei Fang、Mei Liu、Sixun Peng、Hong Liao、Jochen Lehmann、Yihua Zhang

  DOI：10.1021/jm300106z

  日期：2012.5.10

  In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine-ferulic acid-NO donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine.