N-Methyl-N-4-piperidinyl-benzeneacetamide | 868764-37-8

• 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-Methyl-N-4-piperidinyl-benzeneacetamide
• 英文别名: N-methyl-2-phenyl-N-piperidin-4-ylacetamide
• CAS: 868764-37-8
• 化学式: C₁₄H₂₀N₂O
• 分子量: 232.326
• InChiKey: IQUSNBBJHGNARO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-bromopropyl)-2H-benzo[b][1,4]oxazin-3(4H)-one 、 N-Methyl-N-4-piperidinyl-benzeneacetamide 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-methyl-N-{1-[3-(3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propyl]-piperidin-4-yl}-2-phenyl-acetamide
  参考文献：
  名称：

  Discovery of N-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An Allosteric Muscarinic M₁ Receptor Agonist with Unprecedented Selectivity and Procognitive Potential

  摘要：

  The discovery and structure activity relationship (SAR) of a series of allosteric muscarinic M, receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M-1 receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.

  DOI：

  10.1021/jm100697g
• 作为产物：
  描述：

  tert-butyl 4-(N-methyl-2-phenylacetamido)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-Methyl-N-4-piperidinyl-benzeneacetamide
  参考文献：
  名称：

  新型GPR119激动剂的发现，优化和体内评估

  摘要：

  GPR119越来越被视为治疗II型糖尿病和代谢综合征其他成分的有吸引力的靶标。在一项旨在开发GPR119受体激动剂的计划中，我们鉴定了具有降低hERG抑制作用的有效化合物，具有良好的药代动力学特性以及在体内具有出色的降糖效果的化合物。但是，在GPR119敲除（KO）小鼠模型中进行的进一步分析显示，其生物学效应并不完全是由于GPR119激动作用，这突出了转基因动物在药物发现计划中的价值。

  DOI：

  10.1016/j.bmcl.2011.10.033

文献信息

• Discovery of <i>N</i>-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An Allosteric Muscarinic M₁ Receptor Agonist with Unprecedented Selectivity and Procognitive Potential
  作者：Anette G. Sams、Morten Hentzer、Gitte K. Mikkelsen、Krestian Larsen、Christoffer Bundgaard、Niels Plath、Claus T. Christoffersen、Benny Bang-Andersen

  DOI：10.1021/jm100697g

  日期：2010.9.9

  The discovery and structure activity relationship (SAR) of a series of allosteric muscarinic M, receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M-1 receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.
• Discovery, optimisation and in vivo evaluation of novel GPR119 agonists
  作者：Katy J. Brocklehurst、Anders Broo、Roger J. Butlin、Hayley S. Brown、David S. Clarke、Öjvind Davidsson、Kristin Goldberg、Sam D. Groombridge、Elizabeth E. Kelly、Andrew Leach、Darren McKerrecher、Charles O’Donnell、Simon Poucher、Paul Schofield、James S. Scott、Joanne Teague、Leanne Westgate、Matt J.M. Wood

  DOI：10.1016/j.bmcl.2011.10.033

  日期：2011.12

  GPR119 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. During a programme aimed at developing agonists of the GPR119 receptor, we identified compounds that were potent with reduced hERG liabilities, that had good pharmacokinetic properties and that displayed excellent glucose-lowering effects in vivo. However, further

  GPR119越来越被视为治疗II型糖尿病和代谢综合征其他成分的有吸引力的靶标。在一项旨在开发GPR119受体激动剂的计划中，我们鉴定了具有降低hERG抑制作用的有效化合物，具有良好的药代动力学特性以及在体内具有出色的降糖效果的化合物。但是，在GPR119敲除（KO）小鼠模型中进行的进一步分析显示，其生物学效应并不完全是由于GPR119激动作用，这突出了转基因动物在药物发现计划中的价值。