methyl (E)-3-(4-(3-bromopropoxy)-3-methoxyphenyl)acrylate | 1374414-06-8

• 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-(3-bromopropoxy)-3-methoxyphenyl)acrylate
• 英文别名: methyl (E)-3-[4-(3-bromopropoxy)-3-methoxyphenyl]prop-2-enoate
• CAS: 1374414-06-8
• 化学式: C₁₄H₁₇BrO₄
• 分子量: 329.191
• InChiKey: QWCDOBRCMFRZEK-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(4-(3-bromopropoxy)-3-methoxyphenyl)acrylate 在 水 、 silver nitrate 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 54.5h， 生成 3-{2-methoxy-4-[(1E)-3-oxo-3-(3-(1,2,3,4-tetrahydroacridin-9-ylamino)propylamino)prop-1-enyl]phenoxy}propyl nitrate
  参考文献：
  名称：

  Tacrine–Ferulic Acid–Nitric Oxide (NO) Donor Trihybrids as Potent, Multifunctional Acetyl- and Butyrylcholinesterase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm300106z
• 作为产物：
  描述：

  阿魏酸 在 硫酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 methyl (E)-3-(4-(3-bromopropoxy)-3-methoxyphenyl)acrylate
  参考文献：
  名称：

  作为抗阿尔茨海默病多功能候选药物的新型他克林-阿魏酸杂合体的设计、合成和评价

  摘要：

  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。

  DOI：

  10.3390/molecules21101338

文献信息

• Hydroxamic Acid Derivatives of β-Carboline/Hydroxycinnamic Acid Hybrids Inducing Apoptosis and Autophagy through the PI3K/Akt/mTOR Pathways
  作者：Yong Ling、Yangyang Li、Rui Zhu、Jianqiang Qian、Ji Liu、Weijie Gao、Chi Meng、Jiefei Miao、Biao Xiong、Xiaodong Qiu、Changchun Ling、Hong Dai、Yanan Zhang

  DOI：10.1021/acs.jnatprod.8b00843

  日期：2019.6.28

  against four human cancer cells. In particular, 12b showed the highest cytotoxic potency of the series, including drug-resistant Bel7402 cells, but had minimal effect on normal hepatic LO2 cells. These compounds also showed excellent inhibitory effects against HDAC1/6, which appear to contribute greatly to their antiproliferative properties. Compound 12b enhanced the acetylation levels of histone H3 and α-tubulin

  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
• Design and synthesis of rosiglitazone-ferulic acid-nitric oxide donor trihybrids for improving glucose tolerance
  作者：Jingchao Liu、Zhangjian Huang、Wenhuan Ma、Sixun Peng、Yunman Li、Katrina M. Miranda、Jide Tian、Yihua Zhang

  DOI：10.1016/j.ejmech.2018.10.006

  日期：2019.1

  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.