6-bromo-N-(4-methylcyclohexyl)-1-(2-morpholinoethyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-bromo-N-(4-methylcyclohexyl)-1-(2-morpholinoethyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide
• 英文别名: 6-bromo-N-(4-methylcyclohexyl)-1-(2-morpholin-4-ylethyl)-2-oxo-1,8-naphthyridine-3-carboxamide
• 化学式: C₂₂H₂₉BrN₄O₃
• 分子量: 477.401
• InChiKey: FWNMCSJUCLCGGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  74.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-bromo-N-(4-methylcyclohexyl)-1-(2-morpholinoethyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide 、 三正丁基2-吡啶基锌 在 四(三苯基膦)钯 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以9 mg的产率得到N-(4-methylcyclohexyl)-1-(2-morpholinoethyl)-2-oxo-6-(pyridin-2-yl)-1,2-dihydro-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  [EN] CANNABINOID RECEPTOR TYPE 2 (CB2) MODULATORS AND USES THEREOF
  [FR] MODULATEURS DE RÉCEPTEUR CANNABINOÏDE DE TYPE 2 (CB2) ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2021226206A3
• 作为产物：
  描述：

  2-氨基-5-溴烟醛 在 哌啶 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 生成 6-bromo-N-(4-methylcyclohexyl)-1-(2-morpholinoethyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  [EN] CANNABINOID RECEPTOR TYPE 2 (CB2) MODULATORS AND USES THEREOF
  [FR] MODULATEURS DE RÉCEPTEUR CANNABINOÏDE DE TYPE 2 (CB2) ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2021226206A3

文献信息

• Development of selective, fluorescent cannabinoid type 2 receptor ligands based on a 1,8-naphthyridin-2-(1<i>H</i>)-one-3-carboxamide scaffold
  作者：Anna G. Cooper、Caitlin R. M. Oyagawa、Jamie J. Manning、Sameek Singh、Sarah Hook、Natasha L. Grimsey、Michelle Glass、Joel D. A. Tyndall、Andrea J. Vernall

  DOI：10.1039/c8md00448j

  日期：——

  Cannabinoid type 2 (CB2) receptor has been implicated in several diseases and conditions, however no CB2 receptor selective drugs have made it to market. The aim of this study was to develop fluorescent ligands as CB2 receptor tools, to enable an increased understanding of CB2 receptor expression and signalling and thereby accelerate drug discovery. Fluorescent ligands have been successfully developed

  2 型大麻素 (CB 2 ) 受体与多种疾病和病症有关，但尚未有 CB 2受体选择性药物上市。本研究的目的是开发荧光配体作为 CB 2受体工具，以加深对 CB 2受体表达和信号传导的了解，从而加速药物发现。已成功开发出针对其他受体的荧光配体，但尚未报道针对 CB 2受体具有足够的亚型选择性或成像特性的荧光配体。开发了一系列 1,8-萘啶-2-(1 H )-one-3-甲酰胺，其 N1 和 C3 位上附加有连接基和荧光团。分子模型表明，C3顺式环己醇连接的化合物将接头引出跨膜螺旋 1 和 7 之间的 CB 2受体。在此，我们报告荧光配体32 (hCB 2 p K = 6.33 ± 0.02) 是亲和力最高的配体之一，报道了选择性CB 2受体荧光配体。尽管32对 CB 2受体的特异性标记较差，但具有该接头的萘啶支架对于 CB 2受体工具的未来开发仍然非常有希望。
• CB2-Selective Cannabinoid Receptor Ligands: Synthesis, Pharmacological Evaluation, and Molecular Modeling Investigation of 1,8-Naphthyridin-2(1<i>H</i>)-one-3-carboxamides
  作者：Valentina Lucchesi、Dow P. Hurst、Derek M. Shore、Simone Bertini、Brandie M. Ehrmann、Marco Allarà、Lyle Lawrence、Alessia Ligresti、Filippo Minutolo、Giuseppe Saccomanni、Haleli Sharir、Marco Macchia、Vincenzo Di Marzo、Mary E. Abood、Patricia H. Reggio、Clementina Manera

  DOI：10.1021/jm500807e

  日期：2014.11.13

  We have recently identified 1,8-naphthyridin-2(1H)-one-3-carboxamide as a new scaffold very suitable for the development of new CB2 receptor potent and selective ligands. In this paper we describe a number of additional derivatives in which the same central scaffold has been variously functionalized in position 1 or 6. All new compounds showed high selectivity and affinity in the nanomolar range for the CB2 receptor. Furthermore, we found that their functional activity is controlled by the presence of the substituents at position C-6 of the naphthyridine scaffold. In fact, the introduction of substituents in this position determined a functionality switch from agonist to antagonists/inverse agonists. Finally, docking studies showed that the difference between the pharmacology of these ligands may be in the ability/inability to block the Toggle Switch W6.48(258) (chi 1 g+ -> trans) transition