7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid [2-(4-hydroxyphenyl)ethyl]amide

• 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: 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid [2-(4-hydroxyphenyl)ethyl]amide
• 英文别名: N-[2-(4-hydroxyphenyl)ethyl]-7-methoxy-2-oxo-8-pentoxy-1H-quinoline-3-carboxamide
• 化学式: C₂₄H₂₈N₂O₅
• 分子量: 424.497
• InChiKey: AIRPNQJNJIBMOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid [2-(4-hydroxyphenyl)ethyl]amide 、 [11C]methyl triflate 在 sodium hydroxide 作用下， 以 水 、 乙腈 为溶剂， 生成 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid [2-(4-[(11)C]methoxyphenyl)ethyl]amide
  参考文献：
  名称：

  碳-11-标记的喹啉衍生物作为大麻素CB2受体成像的新候选PET放射性配体的合成及体外生物学评价

  摘要：

  最近有人提出将大麻素作为潜在的抗肿瘤药物的新家族，并且认为大麻素受体2（CB2）在肿瘤细胞中过表达。这项研究旨在利用生物医学成像技术正电子发射断层扫描（PET）开发用于癌症中CB2受体成像的新型放射性配体。碳11标记的2-氧喹啉和2-氯喹啉衍生物[ 11 C] 6a - d和[ 11 C] 9a - d是通过使用[ 11 C] CH对相应的前体进行O- [ 11 C]甲基化制备的3OTf在基本条件下并通过简化的固相萃取（SPE）方法进行分离，以[ 11 C] CO 2为基础，以40％至50％的放射化学收率进行了分离，并将衰变校正为轰击结束（EOB）。EOB的总合成时间为15–20分钟，放射化学纯度> 99％，合成结束时的比活（EOS）为111–185 GBq /μmol。放射性配体结合试验表明，化合物6f，6b和9f表现出强大的体外结合亲和力，纳摩尔摩尔K i值，对CB2的选择性至少100-2000倍。

  DOI：

  10.1016/j.bmc.2010.02.011
• 作为产物：
  描述：

  7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 3.0h， 生成 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid [2-(4-hydroxyphenyl)ethyl]amide
  参考文献：
  名称：

  Synthesis and SAR Studies of 2-Oxoquinoline Derivatives as CB2 Receptor Inverse Agonists

  摘要：

  The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.

  DOI：

  10.1021/jm050879z

文献信息

• Synthesis and SAR Studies of 2-Oxoquinoline Derivatives as CB2 Receptor Inverse Agonists
  作者：Katri H. Raitio、Juha R. Savinainen、Jouko Vepsäläinen、Jarmo T. Laitinen、Antti Poso、Tomi Järvinen、Tapio Nevalainen

  DOI：10.1021/jm050879z

  日期：2006.3.1

  The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and effective CB2 receptor inverse agonists. A series of aromatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid 6 was synthesized, and the CB2 receptor activities of the compounds were determined by a [S-35]GTP(gamma)S-binding assay using membranes of CHO cells stably transfected with the human CB2 receptor. As a result, all the compounds were defined as full CB2 receptor inverse agonists, and additionally, except for two 3,4-dihydroxyphenylalkylamides, they were found to be equally potent as SR144528.
• Synthesis and in vitro biological evaluation of carbon-11-labeled quinoline derivatives as new candidate PET radioligands for cannabinoid CB2 receptor imaging
  作者：Mingzhang Gao、Min Wang、Kathy D. Miller、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1016/j.bmc.2010.02.011

  日期：2010.3

  family of potential antitumor agents, and cannabinoid receptor 2 (CB2) is believed to be over-expressed in tumor cells. This study was designed to develop new radioligands for imaging of CB2 receptor in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled 2-oxoquinoline and 2-chloroquinoline derivatives, [11C]6a–d and [11C]9a–d, were prepared by O-[11C]methylation

  最近有人提出将大麻素作为潜在的抗肿瘤药物的新家族，并且认为大麻素受体2（CB2）在肿瘤细胞中过表达。这项研究旨在利用生物医学成像技术正电子发射断层扫描（PET）开发用于癌症中CB2受体成像的新型放射性配体。碳11标记的2-氧喹啉和2-氯喹啉衍生物[ 11 C] 6a - d和[ 11 C] 9a - d是通过使用[ 11 C] CH对相应的前体进行O- [ 11 C]甲基化制备的3OTf在基本条件下并通过简化的固相萃取（SPE）方法进行分离，以[ 11 C] CO 2为基础，以40％至50％的放射化学收率进行了分离，并将衰变校正为轰击结束（EOB）。EOB的总合成时间为15–20分钟，放射化学纯度> 99％，合成结束时的比活（EOS）为111–185 GBq /μmol。放射性配体结合试验表明，化合物6f，6b和9f表现出强大的体外结合亲和力，纳摩尔摩尔K i值，对CB2的选择性至少100-2000倍。