(E)-6-(nitroxy)hexyl 3-(4-hydroxy-3-methoxyphenyl)acrylate | 1257641-83-0

• 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: (E)-6-(nitroxy)hexyl 3-(4-hydroxy-3-methoxyphenyl)acrylate
• 英文别名: 6-nitrooxyhexyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
• CAS: 1257641-83-0
• 化学式: C₁₆H₂₁NO₇
• 分子量: 339.345
• InChiKey: GWXBMFKJRUZRNZ-VQHVLOKHSA-N

物化性质

• 沸点：
  488.9±40.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(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：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-6-(nitroxy)hexyl 3-(4-hydroxy-3-methoxyphenyl)acrylate 在 吡啶 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (E)-6-(nitrooxy)hexyl 3-[3-methoxy-4-((((5-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)benzyl)-2,4-dioxo-3-thiazolidinyl)methoxy)carbonyl)oxy)phenyl]acrylate
  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 silver nitrate 、 三乙胺 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 6.0h， 生成 (E)-6-(nitroxy)hexyl 3-(4-hydroxy-3-methoxyphenyl)acrylate
  参考文献：
  名称：

  发现带有供体NO / H 2 S的3-正丁基邻苯二甲酸酯的开环衍生物作为潜在的抗缺血性卒中剂

  摘要：

  为了寻找比已知药物3-n-丁基邻苯二甲酸酯（NBP）更高效力的新型抗缺血性中风药，NBP的一系列开环衍生物同时带有一氧化氮（NO）和硫化氢（H 2 S）-设计，合成和生物学评估供体部分（NO / H 2 S-NBP）（8a-8o）。活性最高的化合物8d在体外抑制ADP诱导的血小板凝集方面比NBP和相应的H 2 S-NBP 10或NO-NBP 13更有效。另外，8d产生中等水平的NO和H 2S，可能有益于改善心血管和脑循环。更重要的是，在短暂性局灶性脑缺血的大鼠模型中，口服治疗8d改善了神经行为功能，减小了梗塞的大脑大小和脑水含量，并增强了脑抗氧化剂SOD，GSH和GSH-Px的水平，但降低了水平氧化剂MDA。8d对缺血/再灌注（I / R）相关的脑损伤的保护作用大于NBP，这表明8d可能是有希望进行进一步研究的药物。

  DOI：

  10.1016/j.ejmech.2016.03.044

文献信息

• Design and synthesis of novel NO-donor-ferulic acid hybrids as potential antiatherosclerotic drug candidatesa
  作者：Nian-Guang Li、Rong Wang、Zhi-Hao Shi、Yu-Ping Tang、Bao-Quan Li、Zhen-Jiang Wang、Shu-Lin Song、Li-Hua Qian、Li Wei、Jian-Ping Yang、Li-Juan Yao、Jun-Zuan Xi、Jia Xu、Feng Feng、Da-Wei Qian、Jin-Ao Duan

  DOI：10.1002/ddr.20442

  日期：——

  Novel NO‐donor‐ferulic acid hybrids were designed and synthesized through a symbiotic approach using ferulic acid and three different NO‐donating groups, such as nitric ester, 4‐hydroxyl‐3‐phenylfuroxan, and 4‐hydroxymethyl‐3‐phenylsulfonylfuroxan. Antioxidant, nitric oxide release, and vasodilator properties studies showed that the target phenylsulfonylfuroxan 14, especially 14c, while keeping the

  通过使用阿魏酸和三个不同的NO供体基团（例如硝酸酯​​，4-羟基-3-苯基呋喃喃和4-羟基甲基-3-苯基磺酰呋喃喃）通过共生方法设计和合成了新型NO供体-阿魏酸杂交体。抗氧化剂，一氧化氮释放和血管舒张剂的性能研究表明，目标苯磺酰呋喃喃14（尤其是14c）在保持抗氧化剂活性的同时，显示出比硝酸异山梨酯（ISDN）更高的NO释放活性和血管舒张活性。因此，14c可能被认为是一种新型的有效抗动脉粥样硬化药物。Drug Dev Res 72：405–415，2011.©2011 Wiley‐Liss，Inc.
• USE OF NITRIC OXIDE RELEASING COMPOUNDS IN THE TREATMENT OF CHRONIC PAIN
  申请人：Impagnatiello Francesco

  公开号：US20100179192A1

  公开（公告）日：2010-07-15

  The present invention relates to nitrooxyderivative of antioxidant compounds of formula (I) and pharmaceutically acceptable salts or stereoisomers thereof for the treatment of chronic pain, in particular chronic neuropathic pain. The invention also describes composition comprising a nitrooxyderivative of a antioxidant compound of formula (I) and an analgesic drugs.

  本发明涉及公式（I）的抗氧化剂化合物的硝基氧衍生物及其药学上可接受的盐或立体异构体，用于治疗慢性疼痛，特别是慢性神经病性疼痛。本发明还描述了一种包含公式（I）的抗氧化剂化合物的硝基氧衍生物和镇痛药物的组合物。
• 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.
• Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H2S-donating moieties as a potential anti-ischemic stroke agent
  作者：Wei Yin、Li Lan、Zhangjian Huang、Jing Ji、Jiangen Fang、Xiaoli Wang、Hui Ji、Sixun Peng、Jinyi Xu、Yihua Zhang

  DOI：10.1016/j.ejmech.2016.03.044

  日期：2016.6

  To search for novel anti-ischemic stroke agents with higher potency than a known drug 3-n-butylphthalide (NBP), a series of ring-opened derivatives of NBP bearing both nitric oxide (NO) and hydrogen sulfide (H2S)-donating moieties (NO/H2S-NBP) (8a-8o) were designed, synthesized, and biologically evaluated. The most active compound 8d was more potent than NBP and the corresponding H2S-NBP 10 or NO-NBP

  为了寻找比已知药物3-n-丁基邻苯二甲酸酯（NBP）更高效力的新型抗缺血性中风药，NBP的一系列开环衍生物同时带有一氧化氮（NO）和硫化氢（H 2 S）-设计，合成和生物学评估供体部分（NO / H 2 S-NBP）（8a-8o）。活性最高的化合物8d在体外抑制ADP诱导的血小板凝集方面比NBP和相应的H 2 S-NBP 10或NO-NBP 13更有效。另外，8d产生中等水平的NO和H 2S，可能有益于改善心血管和脑循环。更重要的是，在短暂性局灶性脑缺血的大鼠模型中，口服治疗8d改善了神经行为功能，减小了梗塞的大脑大小和脑水含量，并增强了脑抗氧化剂SOD，GSH和GSH-Px的水平，但降低了水平氧化剂MDA。8d对缺血/再灌注（I / R）相关的脑损伤的保护作用大于NBP，这表明8d可能是有希望进行进一步研究的药物。