N,N-二乙基-2-甲基-3-(2-苯基喹啉-4-基)丙酰胺 | 105279-00-3

• 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
• 中文名称: N,N-二乙基-2-甲基-3-(2-苯基喹啉-4-基)丙酰胺
• 英文名称: N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide
• 英文别名: N,N-Diethyl-alpha-methyl-2-phenyl-4-quinolinepropanamide
• CAS: 105279-00-3
• 化学式: C₂₃H₂₆N₂O
• 分子量: 346.472
• InChiKey: HKFDSBSINIWQPC-UHFFFAOYSA-N

物化性质

• 沸点：
  523.2±38.0 °C(Predicted)
• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N,N-二乙基-2-甲基-3-(2-苯基喹啉-4-基)丙酰胺 在 Lux, 12, O₂/A₃, 50:50 作用下， 生成 (R)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide 、 PK 14068
  参考文献：
  名称：

  Development of N-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

  摘要：

  Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat K-i = 0.10 nM; human TSPO genotypes K-i = 1.4 nM; clogD = 4.18).

  DOI：

  10.1021/jm5007947
• 作为产物：
  描述：

  N,N-二乙基丙酰胺 在 正丁基锂 、 silver trifluoromethanesulfonate 、 N,N-二异丙基乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 正己烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 17.0h， 生成 N,N-二乙基-2-甲基-3-(2-苯基喹啉-4-基)丙酰胺
  参考文献：
  名称：

  Development of N-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

  摘要：

  Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat K-i = 0.10 nM; human TSPO genotypes K-i = 1.4 nM; clogD = 4.18).

  DOI：

  10.1021/jm5007947

文献信息

• PERIPHERAL BENZODIAZEPINE RECEPTOR LIGANDS
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：EP1077702A1

  公开（公告）日：2001-02-28
• US4788204A
  申请人：——

  公开号：US4788204A

  公开（公告）日：1988-11-29
• US4788199A
  申请人：——

  公开号：US4788199A

  公开（公告）日：1988-11-29
• [EN] PERIPHERAL BENZODIAZEPINE RECEPTOR LIGANDS<br/>[FR] LIGANDS DE RECEPTEURS PERIPHERIQUE DE LA BENZODIAZEPINE
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：WO1999061024A1

  公开（公告）日：1999-12-02

  (EN) Compounds which bind with high affinity to peripheral benzodiazepine receptors are useful as antiinflammatory agents. Such compounds include isoquinoline derivatives, such as PK 11195, and benzodiazepine derivatives such as Ro 5-4864. A method of treating an inflammatory condition in a mammal with such compounds is provided. Pharmaceutical compositions comprising such compounds are described. A method is provided for identifying compounds that are therapeutically effective for treating inflammatory conditions.(FR) L'invention concerne des composés qui se lient avec forte affinité aux récepteurs périphériques de la benzodiazépine utiles comme agents anti-inflammatoires. Ces composés contiennent des dérivés d'isoquinoline, tels que PK 11195 et des dérivés de benzodiazépine, tels que Ro 5-4864. L'invention concerne également un procédé de traitement d'une maladie inflammatoire chez un mammifère à l'aide de ces composés et des compositions pharmaceutiques renfermant ces composés. Fait aussi l'objet de cette invention un procédé d'identification de composés thérapeutiquement efficaces pour le traitement des maladies inflammatoires.
• Development of <i>N</i>-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)
  作者：Chad Brouwer、Kimberly Jenko、Sami S. Zoghbi、Robert B. Innis、Victor W. Pike

  DOI：10.1021/jm5007947

  日期：2014.7.24

  Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat K-i = 0.10 nM; human TSPO genotypes K-i = 1.4 nM; clogD = 4.18).