[1-(3-methylbenzyl)piperidin-4-ylmethyl]amine | 838814-74-7

• 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: [1-(3-methylbenzyl)piperidin-4-ylmethyl]amine
• 英文别名: {1-[(3-Methylphenyl)methyl]piperidin-4-yl}methanamine；[1-[(3-methylphenyl)methyl]piperidin-4-yl]methanamine
• CAS: 838814-74-7
• 化学式: C₁₄H₂₂N₂
• mdl: MFCD06008186
• 分子量: 218.342
• InChiKey: FIVPCSYIBIUCNE-UHFFFAOYSA-N

物化性质

• 沸点：
  321.2±17.0 °C(Predicted)
• 密度：
  1.006±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [1-(3-methylbenzyl)piperidin-4-ylmethyl]amine 在 盐酸 、 1-羟基-1H-苯并三唑铵盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 2-{[1-(3-methylbenzyl)piperidin-4-yl]methyl}-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide
  参考文献：
  名称：

  Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

  摘要：

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00680
• 作为产物：
  描述：

  哌啶-4-甲酰胺 在 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 生成 [1-(3-methylbenzyl)piperidin-4-ylmethyl]amine
  参考文献：
  名称：

  设计，合成，体外和体内评估苄基哌啶连接的1，3-二甲基苯并咪唑啉酮类化合物作为抗阿尔茨海默氏病的胆碱酯酶抑制剂。

  摘要：

  胆碱酯酶抑制剂在阿尔茨海默氏病（AD）患者的治疗中起着重要作用。在此，我们报告了导致一系列新的1,3-二甲基苯并咪唑啉酮衍生物的药物化学作用。在合成的化合物中，15b和15j对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）表现出亚微摩尔IC50值（15b，eeAChE IC50 = 0.39±0.11 µM； 15j，eqBChE IC50 = 0.16±0.04 µM）。动力学和分子建模研究表明15b和15j以竞争的方式发挥作用。图15b和15j显示了对H 2 O 2诱导的对PC12细胞的氧化损伤的神经保护作用。在体外DPPH分析中确定的抗氧化活性进一步支持了该效果。莫里斯水迷宫测试证实了两种化合物在东induced碱诱导的小鼠模型中的记忆改善作用。此外，15b和15j的肝毒性低于他克林。总之，这些数据表明15b和15j是有希望的抗AD多功能剂。

  DOI：

  10.1080/14756366.2019.1699553

文献信息

• Amidoacridine derivatives useful as selective inhibitors of ubiquitin specific protease 7
  申请人：Hybrigenics S.A.

  公开号：EP2357176A1

  公开（公告）日：2011-08-17

  The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.

  本发明涉及发现新的选择性泛素特异性蛋白酶抑制剂、它们的制备过程及其治疗用途。
• Novel Selective Inhibitors of Ubiquitin Specific Protease 7, the Pharmaceutical Compositions Thereof and Their Therapeutic Applications
  申请人：Lopez Roman

  公开号：US20110177105A1

  公开（公告）日：2011-07-21

  The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.

  本发明涉及发现新的选择性抑制泛素特异性蛋白酶的化合物，以及它们的制备方法和治疗用途。
• NOVEL SELECTIVE INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 7, THE PHARMACEUTICAL COMPOSITIONS THEREOF AND THEIR THERAPEUTIC APPLICATIONS
  申请人：Lopez Roman

  公开号：US20130023521A1

  公开（公告）日：2013-01-24

  The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.

  本发明涉及新型选择性泛素特异性蛋白酶抑制剂的发现，它们的制备过程及其治疗用途。
• AMIDOACRIDINE DERIVATIVES USEFUL AS SELECTIVE INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 7
  申请人：Hybrigenics S.A.

  公开号：EP2523938A1

  公开（公告）日：2012-11-21
• NOVEL AGENTS OF CALCIUM ION CHANNEL MODULATORS
  申请人：Wu Jay Jie-Qiang

  公开号：US20110065703A1

  公开（公告）日：2011-03-17

  The present invention includes a group of chemical compounds useful as modulators of calcium ion (Ca 2+ ) channels, especially for T-type, N-Type and L-type channels. The present invention also includes pharmaceutical compositions comprising these calcium ion channel modulating agents and methods of using these calcium ion channel modulating agents for the treatment diseases and conditions associated with the calcium ion channels.