7-氟-4-氧代-1-戊基-1,4-二氢喹啉-3-羧酸乙酯 | 1048039-27-5

• 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
• 中文名称: 7-氟-4-氧代-1-戊基-1,4-二氢喹啉-3-羧酸乙酯
• 英文名称: ethyl 7-fluoro-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxylate
• CAS: 1048039-27-5
• 化学式: C₁₇H₂₀FNO₃
• 分子量: 305.349
• InChiKey: XKOWZODLYZQYMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  48.3
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  7-氟-4-氧代-1-戊基-1,4-二氢喹啉-3-羧酸乙酯 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 7.0h， 以94%的产率得到7-fluoro-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure−Activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed with Analgesic Activity in Vivo

  摘要：

  Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the ran, e from 55.9 to 0.8 nM and CB1 affinity in the range from > 10 000 to 5.3 nM, with selectivity indeces [K-i(CB1)/K-i(CB2)] varying from > 2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.

  DOI：

  10.1021/jm800552f
• 作为产物：
  描述：

  ethyl 2-(2,4-difluorobenzoyl)-3-(dimethylamino)acrylate 、 1-氨基戊烷 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.42h， 以89%的产率得到7-氟-4-氧代-1-戊基-1,4-二氢喹啉-3-羧酸乙酯
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure−Activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed with Analgesic Activity in Vivo

  摘要：

  Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the ran, e from 55.9 to 0.8 nM and CB1 affinity in the range from > 10 000 to 5.3 nM, with selectivity indeces [K-i(CB1)/K-i(CB2)] varying from > 2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.

  DOI：

  10.1021/jm800552f

文献信息

• Investigations on the 4-quinolone-3-carboxylic acid motif. 6. Synthesis and pharmacological evaluation of 7-substituted quinolone-3-carboxamide derivatives as high affinity ligands for cannabinoid receptors
  作者：Serena Pasquini、Maria De Rosa、Alessia Ligresti、Claudia Mugnaini、Antonella Brizzi、Nicola P. Caradonna、Maria Grazia Cascio、Daniele Bolognini、Roger G. Pertwee、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1016/j.ejmech.2012.09.035

  日期：2012.12

  synthesized and evaluated for their binding ability to cannabinoid type 1 (CB1) and type 2 (CB2) receptors. Most of the compounds showed affinity for one or both cannabinoid receptors at nanomolar concentration, with Ki(CB1) and Ki(CB2) values ranging from 2.45 to >10,000 nM and from 0.09 to 957 nM, respectively. The N-(3,4-dichlorobenzyl)amide derivatives 27 and 40 displayed relatively low affinity, but high

  在我们对4-喹诺酮-3-羧酰胺作为大麻素配体的结构-活性关系的研究中，合成了一系列新化合物，其特征是在7位为氟或苯硫基，在N1和羧酰胺氮上具有不同的取代基，并对其进行了评估。与1型大麻素（CB1）和2型大麻素（CB2）受体的结合能力。大多数化合物在纳摩尔浓度下均显示对一种或两种大麻素受体具有亲和力，其K i（CB1）和K i（CB2）值分别为2.45至> 10,000 nM和0.09至957 nM。所述ñ - （3,4-二氯苄基）酰胺衍生物27和40显示出相对较低的亲和力，但对CB1受体的选择性高。在[ 35 S]GTPγS分析中，化合物4和40分别为CB2和CB1配体充当部分激动剂。它们显示出极低的通过（MDCK-MDR1）细胞的渗透性，因此可能代表了可能的铅结构，可用于进一步优化寻找无法穿越血脑屏障的大麻素配体。