N-(adamantan-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide | 1314230-81-3

• 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
• 英文名称: N-(adamantan-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide
• 英文别名: N-(1-adamantyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide；RS-015；N-(1-adamantyl)-8-methoxy-4-oxo-1H-quinoline-3-carboxamide
• CAS: 1314230-81-3
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: LACXQCASFRBULF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(adamantan-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide 在 potassium fluoride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 生成 N-(1-adamantyl)-1-(2-(2-fluoroethoxy)ethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  发现氟化的4-氧代喹啉衍生物作为潜在的PET放射性示踪剂，用于成像CB2受体。

  摘要：

  2型大麻素受体（CB2）是内源性大麻素系统的一部分，由于其在神经炎性/神经退行性疾病中的重要作用，近年来受到越来越多的关注。最近，我们报道了碳11标记的4-氧代-喹啉衍生物，命名为RS-016，作为使用PET成像CB2的有希望的放射性示踪剂。在这项研究中，设计，合成和药理学评估了三种新颖的RS-016氟化类似物。我们努力的结果导致鉴定出N-（1-金刚烷基）-1-（2-（2-氟乙氧基）乙基）-8-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酰胺（RS -126）作为评估CB2 PET配体的最有力候选者。[18 F] RS-126以> / = 99％的放射化学纯度获得，在放射合成结束时平均比放射性为98 GBq / mumol。[18 F] RS-126的logD7.4值为1.99，在大鼠和人类血浆中在120分钟内在体外稳定，而在注射后10分钟在大鼠血浆中发现55％的完整母体化合物在体内。用CB

  DOI：

  10.1111/jnc.13716
• 作为产物：
  描述：

  8-甲氧基-4-氧代-1,4-二氢喹啉-3-甲酸乙酯 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 N-(adamantan-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  4-oxo-1,4-dihydroquinoline-3-carboxamide as selective ligand for cannabinoid receptor 2 for diagnosis and therapy

  摘要：

  本发明涉及新化合物，其选择性地结合大麻素2受体。此外，该发明涉及利用所述化合物确定大麻素受体2（CB2）选择性受体的定位和密度，优选在中枢神经系统（CNS）、外周神经系统（PNS）、心脏、肝脏、胃肠道、脾脏、胰腺、肾脏、睾丸、卵巢和/或前列腺。此外，该发明涉及利用所述化合物在CB2受体相关疾病的诊断、预防和/或治疗中的应用。

  公开号：

  EP2966062A1

文献信息

• Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 4. Identification of New Potent and Selective Ligands for the Cannabinoid Type 2 Receptor with Diverse Substitution Patterns and Antihyperalgesic Effects in Mice
  作者：Serena Pasquini、Maria De Rosa、Valentina Pedani、Claudia Mugnaini、Francesca Guida、Livio Luongo、Maria De Chiaro、Sabatino Maione、Stefania Dragoni、Maria Frosini、Alessia Ligresti、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm200476p

  日期：2011.8.11

  Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Talcing advantage of previous findings on structure-activity/selectivity relationships for a class of 4-quinolone-3-carboxamides, further structural modifications of the heterocyclic scaffold were explored, leading to the discovery of the 8-methoxy derivative 4a endowed with the highest affinity and selectivity ever reported for a CB2 ligand. The compound, evaluated in vivo in the formalin test, behaved as an inverse agonist by reducing at a dose of 6 mg/kg the second phase of the formalin-induced nocifensive response in mice.
• 4-OXO-1, 4-DIHYDROQUINOLINE-3-CARBOXAMIDE AS SELECTIVE LIGAND FOR CANNABINOID RECEPTOR 2 FOR DIAGNOSIS AND THERAPY
  申请人：ETH ZURICH

  公开号：US20170174632A1

  公开（公告）日：2017-06-22

  The present invention is directed to new compounds selectively binding the cannabinoid 2 receptor. In addition, the invention relates to the use of said compounds for determining cannabinoid receptor 2 (CB2)-selective receptor localization and density, preferably in the central nervous system (CNS), the peripheral nervous system (PNS), heart, liver, gastrointestinal tract, spleen, pancreas, kidney, testis, ovary and/or the prostate. Moreover, the invention pertains to the use of said compounds in the diagnosis, prophylaxis and/or therapy of CB2 receptor-related diseases.
• [EN] 4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXAMIDE AS SELECTIVE LIGAND FOR CANNABINOID RECEPTOR 2 FOR DIAGNOSIS AND THERAPY<br/>[FR] 4-OXO-1,4-DIHYDROQUINOLÉINE-3-CARBOXAMIDE UTILISÉ COMME LIGAND SÉLECTIF POUR LE RÉCEPTEUR DE CANNABINOÏDES 2 POUR LE DIAGNOSTIC ET LA THERAPIE
  申请人：ETH ZUERICH

  公开号：WO2016005419A1

  公开（公告）日：2016-01-14

  The present invention is directed to new compounds of formula (I) selectively binding the cannabinoid 2 receptor. In addition, the invention relates to the use of said compounds for determining cannabinoid receptor 2 (CB2)-selective receptor localization and density, preferably in the central nervous system (CNS), the peripheral nervous system (PNS), heart, liver, gastrointestinal tract, spleen, pancreas, kidney, testis, ovary and/or the prostate. Moreover, the invention pertains to the use of said compounds in the diagnosis, prophylaxis and/or therapy of CB2 receptor-related diseases.
• Discovery of a fluorinated 4-oxo-quinoline derivative as a potential positron emission tomography radiotracer for imaging cannabinoid receptor type 2
  作者：Roger Slavik、Adrienne Müller Herde、Ahmed Haider、Stefanie D. Krämer、Markus Weber、Roger Schibli、Simon M. Ametamey、Linjing Mu

  DOI：10.1111/jnc.13716

  日期：2016.9

  over 120 min, whereas 55% intact parent compound was found in vivo in rat blood plasma at 10 min post injection. In vitro autoradiographic studies with CB2-positive rat spleen tissue revealed high and blockable binding which was confirmed in in vivo displacement experiments with rats by dynamic PET imaging. Ex vivo biodistribution studies confirmed accumulation of [18 F]RS-126 in rat spleen with a specificity

  2型大麻素受体（CB2）是内源性大麻素系统的一部分，由于其在神经炎性/神经退行性疾病中的重要作用，近年来受到越来越多的关注。最近，我们报道了碳11标记的4-氧代-喹啉衍生物，命名为RS-016，作为使用PET成像CB2的有希望的放射性示踪剂。在这项研究中，设计，合成和药理学评估了三种新颖的RS-016氟化类似物。我们努力的结果导致鉴定出N-（1-金刚烷基）-1-（2-（2-氟乙氧基）乙基）-8-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酰胺（RS -126）作为评估CB2 PET配体的最有力候选者。[18 F] RS-126以> / = 99％的放射化学纯度获得，在放射合成结束时平均比放射性为98 GBq / mumol。[18 F] RS-126的logD7.4值为1.99，在大鼠和人类血浆中在120分钟内在体外稳定，而在注射后10分钟在大鼠血浆中发现55％的完整母体化合物在体内。用CB
• 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective ligand for cannabinoid receptor 2 for diagnosis and therapy
  申请人：ETH Zurich

  公开号：EP2966062A1

  公开（公告）日：2016-01-13

  The present invention is directed to new compounds selectively binding the cannabinoid 2 receptor. In addition, the invention relates to the use of said compounds for determining cannabinoid receptor 2 (CB2)-selective receptor localization and density, preferably in the central nervous system (CNS), the peripheral nervous system (PNS), heart, liver, gastrointestinal tract, spleen, pancreas, kidney, testis, ovary and/or the prostate. Moreover, the invention pertains to the use of said compounds in the diagnosis, prophylaxis and/or therapy of CB2 receptor-related diseases.

  本发明涉及新化合物，其选择性地结合大麻素2受体。此外，该发明涉及利用所述化合物确定大麻素受体2（CB2）选择性受体的定位和密度，优选在中枢神经系统（CNS）、外周神经系统（PNS）、心脏、肝脏、胃肠道、脾脏、胰腺、肾脏、睾丸、卵巢和/或前列腺。此外，该发明涉及利用所述化合物在CB2受体相关疾病的诊断、预防和/或治疗中的应用。