2,2-dimethyl-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanoic acid | 1343498-64-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2,2-dimethyl-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanoic acid
• 英文别名: 2,2-dimethyl-5-[4-[(E)-2-phenylethenyl]phenoxy]pentanoic acid
• CAS: 1343498-64-5
• 化学式: C₂₁H₂₄O₃
• 分子量: 324.42
• InChiKey: VGNDLTSULCNHGL-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲基磺酰胺 、 2,2-dimethyl-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以44%的产率得到2,2-dimethyl-N-(methylsulfonyl)-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanamide
  参考文献：
  名称：

  磺酰亚胺和酰胺衍生物作为新型PPARα拮抗剂：合成，抗增殖活性和对接研究。

  摘要：

  进行了激动剂-拮抗剂转换策略以发现新型的PPARα拮抗剂。已开发出带有磺酰亚胺或酰胺官能团的贝特类的苯二氮杂烯基衍生物。合成了第二系列的化合物，用酰胺或脲部分取代了苯基二氮烯基部分。通过反式激活试验筛选最终化合物，在亚微摩尔浓度下显示出良好的PPARα拮抗作用和选择性。在表达PPARα的癌细胞模型中进行测试时，选定的衍生物会诱导对细胞活力的显着影响。值得注意的是，3c，3d和10e在两种副神经节瘤细胞系中均表现出显着的抗增殖作用，其CC50低于商业PPARα拮抗剂GW6471，并且对正常成纤维细胞的毒性可忽略不计。

  DOI：

  10.1021/acsmedchemlett.9b00666
• 作为产物：
  描述：

  ethyl 2,2-dimethyl-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanoate 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以80%的产率得到2,2-dimethyl-5-{4-[(E)-2-phenylvinyl]phenoxy}pentanoic acid
  参考文献：
  名称：

  Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism

  摘要：

  A new series of gemfibrozil analogues conjugated with alpha-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPAR alpha agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPAR alpha receptor and were also screened for their activity on PPAR alpha-regulated gene CPT1A. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.022

文献信息

• Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism
  作者：Barbara De Filippis、Antonella Giancristofaro、Alessandra Ammazzalorso、Alessandra D’Angelo、Marialuigia Fantacuzzi、Letizia Giampietro、Cristina Maccallini、Michele Petruzzelli、Rosa Amoroso

  DOI：10.1016/j.ejmech.2011.08.022

  日期：2011.10

  A new series of gemfibrozil analogues conjugated with alpha-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPAR alpha agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPAR alpha receptor and were also screened for their activity on PPAR alpha-regulated gene CPT1A. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Sulfonimide and Amide Derivatives as Novel PPARα Antagonists: Synthesis, Antiproliferative Activity, and Docking Studies
  作者：Alessandra Ammazzalorso、Isabella Bruno、Rosalba Florio、Laura De Lellis、Antonio Laghezza、Carmen Cerchia、Barbara De Filippis、Marialuigia Fantacuzzi、Letizia Giampietro、Cristina Maccallini、Paolo Tortorella、Serena Veschi、Fulvio Loiodice、Antonio Lavecchia、Alessandro Cama、Rosa Amoroso

  DOI：10.1021/acsmedchemlett.9b00666

  日期：2020.5.14

  An agonist-antagonist switching strategy was performed to discover novel PPARα antagonists. Phenyldiazenyl derivatives of fibrates were developed, bearing sulfonimide or amide functional groups. A second series of compounds was synthesized, replacing the phenyldiazenyl moiety with amide or urea portions. Final compounds were screened by transactivation assay, showing good PPARα antagonism and selectivity

  进行了激动剂-拮抗剂转换策略以发现新型的PPARα拮抗剂。已开发出带有磺酰亚胺或酰胺官能团的贝特类的苯二氮杂烯基衍生物。合成了第二系列的化合物，用酰胺或脲部分取代了苯基二氮烯基部分。通过反式激活试验筛选最终化合物，在亚微摩尔浓度下显示出良好的PPARα拮抗作用和选择性。在表达PPARα的癌细胞模型中进行测试时，选定的衍生物会诱导对细胞活力的显着影响。值得注意的是，3c，3d和10e在两种副神经节瘤细胞系中均表现出显着的抗增殖作用，其CC50低于商业PPARα拮抗剂GW6471，并且对正常成纤维细胞的毒性可忽略不计。