2-(4-乙酰氧基-2-氟-联苯-4-基)-丙酸甲酯 | 215175-84-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-乙酰氧基-2-氟-联苯-4-基)-丙酸甲酯
• 中文别名: 2-（4'-乙酰氧基-2-氟联苯-4-基）-丙酸甲酯；2-[[[3-(三氟甲基)苯基]氨基]苯甲酸8-羟基-3,6-二氧杂辛酯
• 英文名称: methyl 2-(4'-acetoxy-2-fluorobiphenyl-4-yl)propanoate
• 英文别名: 2-(4'-Acetoxy-2-fluoro-biphenyl-4-YL)-propionic acid methyl ester；methyl 2-[4-(4-acetyloxyphenyl)-3-fluorophenyl]propanoate
• CAS: 215175-84-1
• 化学式: C₁₈H₁₇FO₄
• 分子量: 316.329
• InChiKey: PPSZEZRRJWMPME-UHFFFAOYSA-N

物化性质

• 沸点：
  401.2±45.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、可溶于二氯甲烷、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-乙酰氧基-2-氟-联苯-4-基)-丙酸甲酯 在 lithium hydroxide monohydrate 、 硫酸 、 水 、 potassium carbonate 、 silver nitrate 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 59.5h， 生成 6-{2'-fluoro-4'-[1-oxo-1-(4-(1,2,3,4-tetrahydroacridin-9-ylamino)butylamino)propan-2-yl]biphenyl-4-yloxy}hexyl nitrate
  参考文献：
  名称：

  NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity

  摘要：

  To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target compounds showed selective butyrylcholinesterase (BuChE) inhibitory activity in vitro comparable or higher than tacrine and the tacrine-flurbiprofen hybrid compounds 1a-c, and released moderate amount of NO in vitro. The kinetic study suggests that one of the most active and highest BuChE selective compounds 2d may not only compete with the substrate for the same catalytic active site (CAS) but also interact with a second binding site. Furthermore, 2d and 2l exhibited significant vascular relaxation effect, which is beneficial for the treatment of AD. All the results suggest that 2d and 2l might be promising lead compounds for further research. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.008
• 作为产物：
  描述：

  氟比洛芬 在 aluminum (III) chloride 、 硫酸 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 76.5h， 生成 2-(4-乙酰氧基-2-氟-联苯-4-基)-丙酸甲酯
  参考文献：
  名称：

  设计，合成和评估4'-OH-氟比洛芬-查耳酮杂种作为阿尔茨海默氏病治疗的潜在多功能剂

  摘要：

  设计，合成和评估了一系列4'-OH-氟比洛芬-查耳酮杂种，作为治疗阿尔茨海默氏病的潜在多功能剂。生物学筛选结果表明，这些杂种大多数表现出良好的多功能活性。其中化合物7K和7米表现出对自感应甲最好抑制作用β 1-42聚集（60.0％分别和78.2％，）和Cu 2+诱导的阿β 1-42聚集（52.4％和95.0％，分别）。此外，这两种代表性化合物在体外还表现出良好的抗氧化活性，MAO抑制作用，生物金属螯合能力和抗神经炎活性。。此外，化合物7m表现出适当的血脑屏障通透性。这些多功能特性突显了化合物7k和7m是进一步开发抗AD多功能药物的有希望的候选物。

  DOI：

  10.1016/j.bmc.2018.01.030

文献信息

• Discovery of 4′-OH-flurbiprofen Mannich base derivatives as potential Alzheimer’s disease treatment with multiple inhibitory activities
  作者：Hongyan Liu、Xiaoming Qiang、Qing Song、Wei Li、Yuxi He、Chanyuan Ye、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.bmc.2019.01.040

  日期：2019.3

  A series of 4'-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (65.03% at

  设计，合成和评估了一系列4'-OH氟比洛芬曼尼希碱衍生物，作为治疗阿尔茨海默氏病的潜在多功能剂。生物学筛选结果表明，这些衍生物大多数表现出良好的多功能活性。其中，化合物8n对自诱导的Aβ1-42聚集表现出最佳的抑制作用（在25.0μM时为65.03％）。此外，该代表性化合物在体外还表现出良好的抗氧化活性，生物金属螯合能力和抗神经炎活性。此外，化合物8n显示出适当的血脑屏障渗透性。这些多功能特性突出了化合物8n作为抗AD多功能药物进一步开发的有希望的候选物。
• Isoxazole derivatives
  申请人：Sumitomo Pharmaceutical Company, Limited

  公开号：US06100260A1

  公开（公告）日：2000-08-08

  An isoxazole derivative represented by the formula: ##STR1## or a pharmaceutically acceptable salt thereof useful as a therapeutic drug for auto-immune diseases and inflammatory diseases.

  一种由以下结构表示的异噁唑衍生物：##STR1##或其药用可接受的盐，用作治疗自身免疫疾病和炎症性疾病的药物。
• Design, synthesis and evaluation of tacrine–flurbiprofen–nitrate trihybrids as novel anti-Alzheimer’s disease agents
  作者：Yao Chen、Jianfei Sun、Zhangjian Huang、Hong Liao、Sixun Peng、Jochen Lehmann、Yihua Zhang

  DOI：10.1016/j.bmc.2013.03.005

  日期：2013.5

  To search for multifunctional anti-Alzheimer's disease (AD) agents with good safety, the previously synthesized tacrine-flurbiprofen hybrids 1a and 1b were modified into tacrine-flurbiprofen-nitrate trihybrids 3a-h. These compounds displayed comparable or higher cholinesterase inhibitory activity relative to the bivalent hybrids. Compound 3a was the most potent, which released moderate NO, exerted blood vessel relaxative activity, and showed significant A beta inhibitory effects whereas tacrine and flurbiprofen did not exhibit any Ab inhibitory activity at the same dose. In addition, 3a was active in improving memory impairment in vivo. More importantly, the hepatotoxicity study showed that 3a was much safer than tacrine, suggesting it might be a promising anti-AD agent for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.
• US6100260A
  申请人：——

  公开号：US6100260A

  公开（公告）日：2000-08-08
• NO-donating tacrine derivatives as potential butyrylcholinesterase inhibitors with vasorelaxation activity
  作者：Yao Chen、Jianfei Sun、Zhangjian Huang、Hong Liao、Sixun Peng、Jochen Lehmann、Yihua Zhang

  DOI：10.1016/j.bmcl.2013.04.008

  日期：2013.6

  To search for potent anti-Alzheimer's disease (AD) agents with multifunctional effects, 12 NO-donating tacrine-flurbiprofen hybrid compounds (2a-l) were synthesized and biologically evaluated. It was found that all the new target compounds showed selective butyrylcholinesterase (BuChE) inhibitory activity in vitro comparable or higher than tacrine and the tacrine-flurbiprofen hybrid compounds 1a-c, and released moderate amount of NO in vitro. The kinetic study suggests that one of the most active and highest BuChE selective compounds 2d may not only compete with the substrate for the same catalytic active site (CAS) but also interact with a second binding site. Furthermore, 2d and 2l exhibited significant vascular relaxation effect, which is beneficial for the treatment of AD. All the results suggest that 2d and 2l might be promising lead compounds for further research. (C) 2013 Elsevier Ltd. All rights reserved.