N-cycloheptyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide | 1375112-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-cycloheptyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide
• 英文别名: N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-2-oxopyridine-3-carboxamide；N-cyclohepthyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide；N-cycloheptyl-1-[(4-fluorophenyl)methyl]-2-oxopyridine-3-carboxamide
• CAS: 1375112-57-4
• 化学式: C₂₀H₂₃FN₂O₂
• 分子量: 342.413
• InChiKey: CTOOWHZBGXSIAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-cycloheptyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide 在 copper(l) iodide 、 溴 、 lithium bromide 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 18.0h， 生成 5-bromo-N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-2-oxo-4-phenylpyridine-3-carboxamide
  参考文献：
  名称：

  Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system

  摘要：

  The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (K-i = 23.1 nM, partial agonist) and CB2R (K-i = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC50 = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC50 = 2.5 mu M). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC50 values (0.28-0.62 mu M). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.019
• 作为产物：
  描述：

  2-羟基烟酸 在 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.5h， 生成 N-cycloheptyl-1-(p-fluorobenzyl)-1,2-dihydro-2-oxo-pyridine-3-carboxamide
  参考文献：
  名称：

  Polypharmacological profile of 1,2-dihydro-2-oxo-pyridine-3-carboxamides in the endocannabinoid system

  摘要：

  The endocannabinoid system (ECS) represents one of the major neuromodulatory systems involved in different physiological and pathological processes. Multi-target compounds exert their activities by acting via multiple mechanisms of action and represent a promising pharmacological modulation of the ECS. In this work we report 4-substituted and 4,5-disubstituted 1,2-dihydro-2-oxo-pyridine-3-carboxamide derivatives with a broad spectrum of affinity and functional activity towards both cannabinoid receptors and additional effects on the main components of the ECS. In particular compound B3 showed high affinity for CB1R (K-i = 23.1 nM, partial agonist) and CB2R (K-i = 6.9 nM, inverse agonist) and also significant inhibitory activity (IC50 = 70 nM) on FAAH with moderate inhibition of ABHD12 (IC50 = 2.5 mu M). Compounds B4, B5 and B6 that act as full agonists at CB1R and as partial agonists (B5 and B6) or antagonist (B4) at CB2R, exhibited an additional multi-target property by inhibiting anandamide uptake with sub-micromolar IC50 values (0.28-0.62 mu M). The best derivatives showed cytotoxic activity on U937 lymphoblastoid cells. Finally, molecular docking analysis carried out on the three-dimensional structures of CB1R and CB2R and of FAAH allowed to rationalize the structure-activity relationships of this series of compounds. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.019

文献信息

• Rational design, synthesis and anti-proliferative properties of new CB2 selective cannabinoid receptor ligands: An investigation of the 1,8-naphthyridin-2(1H)-one scaffold
  作者：Clementina Manera、Giuseppe Saccomanni、Anna Maria Malfitano、Simone Bertini、Francesca Castelli、Chiara Laezza、Alessia Ligresti、Valentina Lucchesi、Tiziano Tuccinardi、Flavio Rizzolio、Maurizio Bifulco、Vincenzo Di Marzo、Antonio Giordano、Marco Macchia、Adriano Martinelli

  DOI：10.1016/j.ejmech.2012.03.031

  日期：2012.6

  heterocyclic derivatives, characterized by different central cores, were synthesized and tested for their affinity toward the human CB1 and CB2 cannabinoid receptors. The obtained results suggest that the new series of quinolin-2(1H)-on-3-carboxamides, 4-hydroxy-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamides and 1,2-dihydro-2-oxopyridine-3-carboxamides represent novel scaffolds very suitable for the development

  由于该受体在几种生理病理过程中的潜在作用，其CB2受体配体正变得越来越有吸引力。使用我们先前描述的一系列1,8-萘啶-2（1 H）-on-3-羧酰胺类作为先导类，合成了几种具有不同中心核的氮杂环衍生物，并测试了它们对人CB1的亲和力和CB2大麻素受体。获得的结果表明，新系列的喹啉2（1 H-on-3-羧酰胺，4-羟基-2-氧代-1,2-二氢-1,8-萘吡啶-3-羧酰胺和1,2-二氢-2-氧吡啶-3-羧酰胺代表非常合适的新型支架用于开发有前途的CB2配体。此外，新合成的CB2配体抑制了几种癌细胞的增殖。特别地，已证明在DU-145细胞系中这些配体发挥CB2介导的抗增殖作用并降低CB2受体表达水平。