3-methyl-N-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide | 1449478-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-methyl-N-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide
• CAS: 1449478-43-6
• 化学式: C₁₅H₁₅F₃N₄O
• 分子量: 324.306
• InChiKey: FVIMVDHOXSWXJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.95
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-methyl-N-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide 、 碘乙烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以62%的产率得到5-ethyl-3-methyl-N-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide
  参考文献：
  名称：

  Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: Synthesis and neuropharmacology

  摘要：

  We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-alpha), nitric oxide and cannabinoid receptor subtype 1 (CBI). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tertbutyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED50 = 23.8 mg/kg) and partial sciatic nerve injury (ED50 = 29.0 mg/kg) models with CB receptor activity (IC50 = 49.6 nM) and inhibitory effect on TNF-alpha (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.022
• 作为产物：
  描述：

  4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 46.0h， 生成 3-methyl-N-(3-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide
  参考文献：
  名称：

  Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: Synthesis and neuropharmacology

  摘要：

  We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-alpha), nitric oxide and cannabinoid receptor subtype 1 (CBI). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tertbutyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED50 = 23.8 mg/kg) and partial sciatic nerve injury (ED50 = 29.0 mg/kg) models with CB receptor activity (IC50 = 49.6 nM) and inhibitory effect on TNF-alpha (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.05.022