5-bromo-N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-2-oxo-4-phenylpyridine-3-carboxamide

• 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: 5-bromo-N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-2-oxo-4-phenylpyridine-3-carboxamide
• 英文别名: 5-bromo-N-cycloheptyl-1-[(4-fluorophenyl)methyl]-2-oxo-4-phenylpyridine-3-carboxamide
• 化学式: C₂₆H₂₆BrFN₂O₂
• 分子量: 497.407
• InChiKey: ASMJTPOFWQZVFN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 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：

  4-甲氧基苯硼酸 、 5-bromo-N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-2-oxo-4-phenylpyridine-3-carboxamide 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以70%的产率得到N-cycloheptyl-1,2-dihydro-1-(4-fluorobenzyl)-5-(4-methoxyphenyl)-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 copper(l) iodide 、 溴 、 sodium hydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.5h， 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