methyl (E)-3-(3-methoxy-4-{[3-(nitrooxy)propyl]oxy}phenyl)acrylate | 1374414-10-4

• 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-(3-methoxy-4-{[3-(nitrooxy)propyl]oxy}phenyl)acrylate
• 英文别名: methyl (E)-3-(3-methoxy-4-(3-(nitrooxy)propoxy)phenyl)acrylate；(E)-methyl 3-{3-methoxy-4-[3-(nitrooxy)propoxy]phenyl}acrylate；methyl (E)-3-[3-methoxy-4-(3-nitrooxypropoxy)phenyl]prop-2-enoate
• CAS: 1374414-10-4
• 化学式: C₁₄H₁₇NO₇
• 分子量: 311.291
• InChiKey: FSCMGNTVRHWBIA-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  22.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.13
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(3-methoxy-4-{[3-(nitrooxy)propyl]oxy}phenyl)acrylate 在 水 、 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 为溶剂， 反应 48.5h， 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：

  methyl (E)-3-(4-(3-bromopropoxy)-3-methoxyphenyl)acrylate 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以73%的产率得到methyl (E)-3-(3-methoxy-4-{[3-(nitrooxy)propyl]oxy}phenyl)acrylate
  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

文献信息

• 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.