4-(4-Methylphenyl)-1-(piperidin-3-ylmethyl)quinolin-2-one | 1426832-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(4-Methylphenyl)-1-(piperidin-3-ylmethyl)quinolin-2-one
• 英文别名: 4-(4-methylphenyl)-1-(piperidin-3-ylmethyl)quinolin-2-one
• CAS: 1426832-11-2
• 化学式: C₂₂H₂₄N₂O
• 分子量: 332.445
• InChiKey: FJCOVBOBUYSQLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-Boc-3-羟甲基哌啶 在 四(三苯基膦)钯 、 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成 4-(4-Methylphenyl)-1-(piperidin-3-ylmethyl)quinolin-2-one
  参考文献：
  名称：

  Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists

  摘要：

  High throughput screening led to the identification of a novel series of quinolone alpha 7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl)quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pK(a). A novel 4-fluoroquinuclidine significantly lowered the pK(a) of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.070

文献信息

• Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists
  作者：Ivar M. McDonald、Robert A. Mate、F. Christopher Zusi、Hong Huang、Debra J. Post-Munson、Meredith A. Ferrante、Lizbeth Gallagher、Robert L. Bertekap、Ronald J. Knox、Barbara J. Robertson、David G. Harden、Daniel G. Morgan、Nicholas J. Lodge、Steven I. Dworetzky、Richard E. Olson、John E. Macor

  DOI：10.1016/j.bmcl.2013.01.070

  日期：2013.3

  High throughput screening led to the identification of a novel series of quinolone alpha 7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl)quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pK(a). A novel 4-fluoroquinuclidine significantly lowered the pK(a) of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay. (C) 2013 Elsevier Ltd. All rights reserved.