benzo[2'-(1-benzyl-4-piperidyl)]hydrazide | 52313-55-0

• 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: benzo[2'-(1-benzyl-4-piperidyl)]hydrazide
• 英文别名: 4-(2-benzoylhydrazino)-1-benzylpiperidine；Benzo(2'-(1-benzyl-4-piperidyl))hydrazide；N'-(1-benzylpiperidin-4-yl)benzohydrazide
• CAS: 52313-55-0
• 化学式: C₁₉H₂₃N₃O
• 分子量: 309.411
• InChiKey: QEUTZPRLLBCXNK-UHFFFAOYSA-N

物化性质

• 沸点：
  426.0±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  benzo[2'-(1-benzyl-4-piperidyl)]hydrazide 在 sodium tetrahydroborate 、 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以32.4 g的产率得到(1-benzyl-piperidin-4-yl)-hydrazine dihydrochloride
  参考文献：
  名称：

  雷帕霉素哺乳动物靶标的ATP竞争性抑制剂：高强度和选择性吡唑并嘧啶的设计和合成

  摘要：

  雷帕霉素（mTOR）的哺乳动物靶标是生长，存活和代谢的主要调节剂，是经过验证的癌症治疗靶标。雷帕霉素及其类似物（mTOR的变构抑制剂）仅部分抑制一种mTOR蛋白复合物。描述了具有增强抗癌功​​效潜力的ATP竞争性mTOR整体抑制剂。鉴定并完善了导致效价和选择性的结构特征，从而在肿瘤异种移植模型中产生了具有体内功效的化合物。

  DOI：

  10.1021/jm900851f
• 作为产物：
  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

文献信息

• Discovery of 4-Morpholino-6-aryl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidines as Highly Potent and Selective ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin (mTOR): Optimization of the 6-Aryl Substituent
  作者：Jeroen C. Verheijen、David J. Richard、Kevin Curran、Joshua Kaplan、Mark Lefever、Pawel Nowak、David J. Malwitz、Natasja Brooijmans、Lourdes Toral-Barza、Wei-Guo Zhang、Judy Lucas、Irwin Hollander、Semiramis Ayral-Kaloustian、Tarek S. Mansour、Ker Yu、Arie Zask

  DOI：10.1021/jm9013828

  日期：2009.12.24

  6-alkylureidophenyl groups with 1-carbamoylpiperidine substitution resulted in compounds with subnanomolar IC50 against mTOR and greater than 1000-fold selectivity over PI3K-α. In addition, structure based drug design resulted in the preparation of several 6-arylureidophenyl-1H-pyrazolo[3,4-d]pyrimidines, substituted in the 4-position of the arylureido moiety with water solubilizing groups. These compounds

  设计和合成了一系列4-吗啉代-6-芳基-1 H-吡唑并[3,4- d ]嘧啶，它们是雷帕霉素（mTOR）哺乳动物靶标的有效和选择性抑制剂。优化6-芳基取代基导致发现带有6-脲基苯基的抑制剂，这是第一个报道的具有亚纳摩尔抑制浓度的mTOR活性位点抑制剂。本文提供的数据表明，6-芳基脲基苯基取代基可产生有效的mTOR和磷脂酰肌醇3-激酶α（PI3K-α）混合抑制剂，而6-烷基脲基苯基附肢则具有高度选择性的mTOR抑制剂。6-烷基脲基苯基与1-氨基甲酰基哌啶取代的组合产生具有亚纳摩尔级IC 50的化合物对mTOR的抗性和对PI3K-α的选择性大于1000倍。另外，基于结构的药物设计导致制备了几种6-芳基脲基苯基-1H-吡唑并[3，4- d ]嘧啶，其在芳基脲基部分的4-位被水溶性基团取代。这些化合物将有效的mTOR抑制（IC 50 <1 nM）与细胞增殖试验（IC 50 <1 nM）中前所未有的活性结合在一起。
• SULFONYLUREIDOPYRAZOLE DERIVATIVES
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0885890A1

  公开（公告）日：1998-12-23

  A sulfonylureidopyrazole derivative of formula (1) or (2) is disclosed. The derivative has an inhibitory activity on endothelin converting enzyme, and is useful for treating or preventing various cardiac failures, tracheal constrictions, nervous disorders, parasecretion, vascular disorders, various ulcers and the like.

  公开了一种化学式（1）或（2）的磺酰脲吡唑衍生物。该衍生物对内皮素转化酶具有抑制活性，可用于治疗或预防各种心脏衰竭、气管收缩、神经紊乱、副分泌、血管紊乱、各种溃疡等疾病。
• 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.
• ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines
  作者：Arie Zask、Jeroen C. Verheijen、Kevin Curran、Joshua Kaplan、David J. Richard、Pawel Nowak、David J. Malwitz、Natasja Brooijmans、Joel Bard、Kristine Svenson、Judy Lucas、Lourdes Toral-Barza、Wei-Guo Zhang、Irwin Hollander、James J. Gibbons、Robert T. Abraham、Semiramis Ayral-Kaloustian、Tarek S. Mansour、Ker Yu

  DOI：10.1021/jm900851f

  日期：2009.8.27

  The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency

  雷帕霉素（mTOR）的哺乳动物靶标是生长，存活和代谢的主要调节剂，是经过验证的癌症治疗靶标。雷帕霉素及其类似物（mTOR的变构抑制剂）仅部分抑制一种mTOR蛋白复合物。描述了具有增强抗癌功​​效潜力的ATP竞争性mTOR整体抑制剂。鉴定并完善了导致效价和选择性的结构特征，从而在肿瘤异种移植模型中产生了具有体内功效的化合物。