N-(4-acetamidobenzyl)-2,4-dihydroxy-N-(4-(piperidine-1-carbonyl)phenyl)benzamide

• 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: N-(4-acetamidobenzyl)-2,4-dihydroxy-N-(4-(piperidine-1-carbonyl)phenyl)benzamide
• 英文别名: N-(4-acetamidobenzyl)-2,4-dihydroxy-N-(4-(piperidin-1-carbonyl)phenyl)benzamide；N-[(4-acetamidophenyl)methyl]-2,4-dihydroxy-N-[4-(piperidine-1-carbonyl)phenyl]benzamide
• 化学式: C₂₈H₂₉N₃O₅
• 分子量: 487.555
• InChiKey: JMHRNFVHLLHMMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二羟基苯甲酸 在 N-甲基吗啉 、 草酰氯 、 硫酸 、 palladium on activated charcoal 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 N-(4-acetamidobenzyl)-2,4-dihydroxy-N-(4-(piperidine-1-carbonyl)phenyl)benzamide
  参考文献：
  名称：

  Identification of Novel Resorcinol Amide Derivatives as Potent and Specific Pyruvate Dehydrogenase Kinase (PDHK) Inhibitors

  摘要：

  Pyruvate dehydrogenase kinases (PDHKs) promote abnormal respiration in cancer cells. Studies with novel resorcinol amide derivatives based on VER-246608 (6) led to the identification of 19n and 19t containing five-membered heteroaromatic rings as unique structural features. These substances possess single-digit nanomolar activities against PDHKs. 19t exhibits higher potencies against PDHK1/2/4 than does 6 and inhibits only PDHKs among 366 kinases. Moreover, 19g, 19l, and 19s were found to be isotype-selective PDHK inhibitors. Molecular dynamics simulations provide a better understanding of how the heteroaromatic rings affect the activities of 19n and 19t on PDHK1/2/3/4. Moreover, 19n possesses a much higher antiproliferative activity against cancer cells than does 6. We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, 19n induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis, and displays a synergistic effect on satraplatin suppression of cancer cell proliferation.

  DOI：

  10.1021/acs.jmedchem.9b00565