(+/-)-2-[1-(2-chloroacetoxy)pentyl]benzoic acid | 1107060-38-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (+/-)-2-[1-(2-chloroacetoxy)pentyl]benzoic acid
• 英文别名: 2-[1-(2-Chloroacetyl)oxypentyl]benzoic acid
• CAS: 1107060-38-7
• 化学式: C₁₄H₁₇ClO₄
• 分子量: 284.74
• InChiKey: MXQMRJZGBMHIEO-UHFFFAOYSA-N

物化性质

• 熔点：
  67-68 °C(Solv: hexane (110-54-3))
• 沸点：
  407.7±30.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-2-[1-(2-chloroacetoxy)pentyl]benzoic acid 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 生成 (+/-)-4-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)butyl 2-(1-(2-(diethylamino) acetoxy)pentyl)benzoate
  参考文献：
  名称：

  设计，合成和生物评价3-正丁基邻苯二甲酸酯的硫化氢释放衍生物作为潜在的抗血小板和抗血栓形成剂。

  摘要：

  在本研究中，设计，合成和生物学评估了一系列的3-正丁基邻苯二甲酸酯（NBP）释放出硫化氢（H2S）的衍生物（8a-g和9a-f）。最有希望的化合物8e在体外显着抑制二磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板凝集，优于NBP，盐酸噻氯匹定和阿司匹林。此外，8e可以在体外缓慢产生中等水平的H2S，这可能有益于改善心血管和脑循环。最重要的是，8e保护了小鼠免受胶原蛋白和肾上腺素诱导的血栓形成，并且在大鼠中显示出比NBP和阿司匹林更大的抗血栓形成活性。总体而言，8e值得进一步研究以治疗血栓形成相关的缺血性中风。

  DOI：

  10.1039/c4ob00830h
• 作为产物：
  描述：

  3-丁基-1(3H)-异苯并呋喃酮 在 4-二甲氨基吡啶 、 水 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 (+/-)-2-[1-(2-chloroacetoxy)pentyl]benzoic acid
  参考文献：
  名称：

  Design, synthesis and evaluation of nitric oxide releasing derivatives of 3-n-butylphthalide as antiplatelet and antithrombotic agents

  摘要：

  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。

  DOI：

  10.1039/c1ob05478c

文献信息

• 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。
• Synthesis and evaluation of nitric oxide-releasing derivatives of 3-n-butylphthalide as anti-platelet agents
  作者：Yang Li、Xuliang Wang、Rong Fu、Wenying Yu、Xiaoli Wang、Yisheng Lai、Sixun Peng、Yihua Zhang

  DOI：10.1016/j.bmcl.2011.05.082

  日期：2011.7

  Most ischemic stroke results from brain blood vessel blockage by platelet-mediated thrombus, and antiplatelet therapy has been demonstrated clinical benefits in the treatment of this disease. In the present work, novel nitric oxide (NO)-releasing derivatives of an anti-ischemic stroke drug 3-n-butylphthalide (NBP) were synthesized. Compounds 7a and 7c exhibited more potent anti-platelet activity than NBP and aspirin, and released a moderate amount of NO, which is beneficial in improving cardiovascular and cerebral circulation. These findings provide an alternative approach to the development of drugs more potent than NBP for the intervention of ischemic stroke. (C) 2011 Elsevier Ltd. All rights reserved.
• Design and synthesis of the ring-opened derivative of 3-n-butylphthalide-ferulic acid-glucose trihybrids as potential anti-ischemic agents
  作者：Jianbing Wu、Wei Yin、Yinqiu Zhang、Hui Ye、Yunman Li、Jide Tian、Zhangjian Huang、Yihua Zhang

  DOI：10.1016/j.cclet.2020.02.031

  日期：2020.7

  To improve aqueous solubility and anti-ischemic activity of 3-n-butylphthalide (NBP), we designed and synthesized the ring-opened derivative of NBP-ferulic acid-glucose trihybrids (S1-S8). These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, S2 was 30-fold more water-soluble, and over 10-fold more potent in inhibition of platelet aggregation, as well as reduced ROS generation and protected primary neuronal cells from OGD/R-induced damage, in comparison with NBP. Additionally, S2 was more active than its three moieties alone or in combination, suggesting that the activity of S2 may be attributed to the synergistic effects of these moieties. Importantly, in vivo studies indicated that S2 not only possessed good pharmacokinetic profile, but also improved NBP distribution in rodent brain, suggesting that the glucose moiety in S2 may be recognized by glucose transporter 1 (GLUT1) on blood-brain barrier (BBB), promoting it to penetrate through BBB. Our findings suggest that S2 may be a promising candidate for the intervention of ischemic stroke, warranting further study. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
• Design, synthesis, and evaluation of n-butylphthalide and ligustrazine hybrids as potent neuroprotective agents for the treatment of ischemic stroke in vitro and in vivo
  作者：Yi Jia、Haiyan Xiao、Xiaolin Wang、Ying Liu、Jiaxin Wang、Haochen Xie、Hai Shang、Guibo Sun、Yu Tian

  DOI：10.1016/j.bioorg.2023.106961

  日期：2024.1