N'-(1-benzylpiperidin-4-ylidene)benzohydrazide | 52313-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N'-(1-benzylpiperidin-4-ylidene)benzohydrazide
• 英文别名: 1-benzyl-piperidin-4-one benzoylhydrazone；N-[(1-benzylpiperidin-4-ylidene)amino]benzamide
• CAS: 52313-53-8
• 化学式: C₁₉H₂₁N₃O
• mdl: MFCD01072256
• 分子量: 307.395
• InChiKey: JEFNDTXEEJIKII-UHFFFAOYSA-N

物化性质

• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.263
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N'-(1-benzylpiperidin-4-ylidene)benzohydrazide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 benzo[2'-(1-benzyl-4-piperidyl)]hydrazide
  参考文献：
  名称：

  Discovery of Potent and Selective Inhibitors of the Mammalian Target of Rapamycin (mTOR) Kinase

  摘要：

  The mammalian target of rapamycin (mTOR) is a central regulator of cell growth, metabolism, and angiogenesis and an emerging target in cancer research. High throughput screening (HTS) of our compound collection led to the identification of 3-(4-morpholin-4-yl-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol (5a), a modestly potent and nonselective inhibitor of mTOR and phosphoinositide 3-kinase (PI3K). Optimization of compound 5a, employing an mTOR homology model based on an X-ray crystal structure of closely related PI3K gamma led to the discovery of 6-(1H-indol-5-yl)-4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine (5u), a potent and selective mTOR inhibitor (mTOR IC50 = 9 nM; PI3K alpha IC50 = 1962 nM). Compound 5u selectively inhibited cellular biomarker of mTORCl (P-S6K, P-4EBP1) and mTORC2 (P-AKT S473) over the biomarker of PI3K/PDK1 (P-AKT T308) and did not inhibit PI3K-related kinases (PIKKs) in cellular assays. These pyrazolopyrimidines represent an exciting new series of mTOR-selective inhibitors with potential for development for cancer therapy.

  DOI：

  10.1021/jm9012642
• 作为产物：
  描述：

  苯甲酸 在 硫酸 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 N'-(1-benzylpiperidin-4-ylidene)benzohydrazide
  参考文献：
  名称：

  具有吡啶和N-苄基哌啶片段的新型铜螯合乙酰胆碱酯酶抑制剂的设计，合成和生物学评估。

  摘要：

  胆碱能耗竭是AD患者中残疾和痴呆的直接原因。AChE是胆碱能疾病的经典和关键靶标。在这项工作中，开发了一些新的结合乙酰吡啶，酰基hydr和N-苄基哌啶片段的AChE抑制剂。优化命中结构以产生具有针对AChE的IC 50值为6.62 nM的化合物21，而几乎对BChE没有抑制作用。ADMET预测和PAMPA渗透性评估显示出良好的类药物性质。具有中间烷基链取代的较高活性表明抑制剂与AChE的新结合方式。这一发现为结合机制提供了新的见解，并有助于发现新型的高活性AChE抑制剂。

  DOI：

  10.1016/j.bioorg.2019.103322

文献信息

• Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine and N-benzylpiperidine fragments
  作者：Yeheng Zhou、Wei Sun、Jiale Peng、Hui Yan、Li Zhang、Xingyong Liu、Zhili Zuo

  DOI：10.1016/j.bioorg.2019.103322

  日期：2019.12

  new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain

  胆碱能耗竭是AD患者中残疾和痴呆的直接原因。AChE是胆碱能疾病的经典和关键靶标。在这项工作中，开发了一些新的结合乙酰吡啶，酰基hydr和N-苄基哌啶片段的AChE抑制剂。优化命中结构以产生具有针对AChE的IC 50值为6.62 nM的化合物21，而几乎对BChE没有抑制作用。ADMET预测和PAMPA渗透性评估显示出良好的类药物性质。具有中间烷基链取代的较高活性表明抑制剂与AChE的新结合方式。这一发现为结合机制提供了新的见解，并有助于发现新型的高活性AChE抑制剂。
• Discovery of Potent and Selective Inhibitors of the Mammalian Target of Rapamycin (mTOR) Kinase
  作者：Pawel Nowak、Derek C. Cole、Natasja Brooijmans、Matthew G. Bursavich、Kevin J. Curran、John W. Ellingboe、James J. Gibbons、Irwin Hollander、YongBo Hu、Joshua Kaplan、David J. Malwitz、Lourdes Toral-Barza、Jeroen C. Verheijen、Arie Zask、Wei-Guo Zhang、Ker Yu

  DOI：10.1021/jm9012642

  日期：2009.11.26

  The mammalian target of rapamycin (mTOR) is a central regulator of cell growth, metabolism, and angiogenesis and an emerging target in cancer research. High throughput screening (HTS) of our compound collection led to the identification of 3-(4-morpholin-4-yl-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol (5a), a modestly potent and nonselective inhibitor of mTOR and phosphoinositide 3-kinase (PI3K). Optimization of compound 5a, employing an mTOR homology model based on an X-ray crystal structure of closely related PI3K gamma led to the discovery of 6-(1H-indol-5-yl)-4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine (5u), a potent and selective mTOR inhibitor (mTOR IC50 = 9 nM; PI3K alpha IC50 = 1962 nM). Compound 5u selectively inhibited cellular biomarker of mTORCl (P-S6K, P-4EBP1) and mTORC2 (P-AKT S473) over the biomarker of PI3K/PDK1 (P-AKT T308) and did not inhibit PI3K-related kinases (PIKKs) in cellular assays. These pyrazolopyrimidines represent an exciting new series of mTOR-selective inhibitors with potential for development for cancer therapy.