(E)-3-bromopropyl-3-(3-methoxy-4-hydroxyphenyl)acrylate | 1257642-03-7

• 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)-3-bromopropyl-3-(3-methoxy-4-hydroxyphenyl)acrylate
• 英文别名: (E)-3-bromopropyl 3-(4-hydroxy-3-methoxyphenyl)acrylate；3-bromopropyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate
• CAS: 1257642-03-7
• 化学式: C₁₃H₁₅BrO₄
• 分子量: 315.164
• InChiKey: FBZHYYRQTSJRNH-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-bromopropyl-3-(3-methoxy-4-hydroxyphenyl)acrylate 在 吡啶 、 silver nitrate 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 (E)-3-(nitrooxy)propyl 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 、 1,3-二溴丙烷 在 三乙胺 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以82%的产率得到(E)-3-bromopropyl-3-(3-methoxy-4-hydroxyphenyl)acrylate
  参考文献：
  名称：

  苯二酚-小ber碱杂种：阿尔茨海默氏病的多功能药物

  摘要：

  我们设计并合成了一系列杂化分子，以通过使小ber碱与苯二醇，褪黑激素和阿魏酸反应来鉴定新型的阿尔茨海默氏病（AD）多功能候选药物。对产品进行以下评估：（i）抑制多种胆碱酯酶（ChEs）的能力；（ii）预防淀粉样β（Aβ）聚集的能力；（iii）抗氧化活性。与先导化合物小ber碱相比，所有衍生物都是更好的抗氧化剂，并在更大程度上抑制了Aβ聚集。尤其是其中的两种杂种，有可能成为AD治疗的优秀候选药物：小ber碱-邻苯二酚杂种（化合物8）是乙酰胆碱酯酶（AChE）的抑制剂，比未结合的小ber碱（IC 50）好得多。：0.123对0.374μM）；小ber碱-对苯二酚杂化物（化合物12）显示出高的抗氧化活性，可以抑制AChE（IC 50为0.460μM），并且具有最大的抑制Aβ聚集的能力。

  DOI：

  10.1016/j.bmc.2011.09.040

文献信息

• Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents
  作者：Xuliang Wang、Yang Li、Qian Zhao、Zhenli Min、Chao Zhang、Yisheng Lai、Hui Ji、Sixun Peng、Yihua Zhang

  DOI：10.1039/c1ob05478c

  日期：——

  Novel nitric oxide (NO) releasing derivatives (7a–7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitroplatelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.

  新设计的硝酸氧化（NO）释放型衍生物（7a–7l）的3-n-丁基亚硝酸酯（NBP）被合成。化合物7e在体外抑制了腺苷二磷酸（ADP）、血栓素（TH）和花生四烯酸（AA）诱导的血小板聚集，优于NBP和阿司匹林，释放适量的NO，相对于NBP提高了水溶性。此外，7e在大鼠中表现出比NBP和阿司匹林更强的抗血栓活性，并保护小鼠免受胶原蛋白和肾上腺素诱导的血栓形成。因此，NO释放型NBP衍生物具有强大的抗血小板聚集和抗血栓活性。我们的发现可能有助于设计用于治疗与血栓形成相关的缺血性中风的新型治疗药物。
• 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.
• 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.
• Benzenediol-berberine hybrids: Multifunctional agents for Alzheimer’s disease
  作者：Huailei Jiang、Xu Wang、Ling Huang、Zonghua Luo、Tao Su、Ke Ding、Xingshu Li

  DOI：10.1016/j.bmc.2011.09.040

  日期：2011.12

  We designed and synthesized a series of hybrid molecules, in an effort to identify novel multifunctional drug candidates for Alzheimer’s disease (AD), by reacting berberine with benzenediol, melatonin, and ferulic acid. The products were evaluated for: (i) the ability to inhibit multiple cholinesterases (ChEs); (ii) the capacity to prevent amyloid β (Aβ) aggregation; and (iii) antioxidant activity

  我们设计并合成了一系列杂化分子，以通过使小ber碱与苯二醇，褪黑激素和阿魏酸反应来鉴定新型的阿尔茨海默氏病（AD）多功能候选药物。对产品进行以下评估：（i）抑制多种胆碱酯酶（ChEs）的能力；（ii）预防淀粉样β（Aβ）聚集的能力；（iii）抗氧化活性。与先导化合物小ber碱相比，所有衍生物都是更好的抗氧化剂，并在更大程度上抑制了Aβ聚集。尤其是其中的两种杂种，有可能成为AD治疗的优秀候选药物：小ber碱-邻苯二酚杂种（化合物8）是乙酰胆碱酯酶（AChE）的抑制剂，比未结合的小ber碱（IC 50）好得多。：0.123对0.374μM）；小ber碱-对苯二酚杂化物（化合物12）显示出高的抗氧化活性，可以抑制AChE（IC 50为0.460μM），并且具有最大的抑制Aβ聚集的能力。