5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)isoxazole-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)isoxazole-3-carboxamide
• 英文别名: 5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)-1,2-oxazole-3-carboxamide
• 化学式: C₁₇H₁₅N₃O₃
• 分子量: 309.324
• InChiKey: UXHPJTUAFYTVJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)isoxazole-3-carboxamide 、 2-甲基苄溴 以 乙腈 为溶剂， 以80%的产率得到3-((5-(4-methoxyphenyl)isoxazole-3-carboxamido)methyl)-1-(2-methylbenzyl)pyridin-1-ium bromide
  参考文献：
  名称：

  Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

  摘要：

  A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC50 = 5.96 mu M) and compound 5j also from the same series of compounds containing phenyl group connected to isoxazole ring demonstrated the most promising inhibitory activity against BChE (IC50, = 0.32 mu M). Also, kinetic study demonstrated competitive inhibition mode for both AChE and BChE inhibitory activity. Docking study was also performed for those compounds and desired interactions with those active site amino acid residues were confirmed through hydrogen bonding as well as pi-pi and pi-anion interactions. In addition, the most potent compounds were tested against BACE1 and their neuroprotectivity on A beta-treated neurotoxicity in PC12 cells which depicted negligible activity. It should be noted that most of the synthesized compounds from both categories 5a-i and 5j-q showed a significant selectivity toward BChE. However, series 5j-q were more active toward AChE than series 5a-i.

  DOI：

  10.1016/j.bioorg.2019.103192
• 作为产物：
  描述：

  5-(4-甲氧苯基)异噻唑-3-羧酸 、 3-氨甲基吡啶 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 24.5h， 生成 5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)isoxazole-3-carboxamide
  参考文献：
  名称：

  Novel N-benzylpyridinium moiety linked to arylisoxazole derivatives as selective butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

  摘要：

  A novel series of N-benzylpyridinium moiety linked to arylisoxazole ring were designed, synthesized, and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Synthesized compounds were classified into two series of 5a-i and 5j-q considering the position of positively charged nitrogen of pyridinium moiety (3- or 4- position, respectively) connected to isoxazole carboxamide group. Among the synthesized compounds, compound 5n from the second series of compounds possessing 2,4-dichloroaryl group connected to isoxazole ring was found to be the most potent AChE inhibitor (IC50 = 5.96 mu M) and compound 5j also from the same series of compounds containing phenyl group connected to isoxazole ring demonstrated the most promising inhibitory activity against BChE (IC50, = 0.32 mu M). Also, kinetic study demonstrated competitive inhibition mode for both AChE and BChE inhibitory activity. Docking study was also performed for those compounds and desired interactions with those active site amino acid residues were confirmed through hydrogen bonding as well as pi-pi and pi-anion interactions. In addition, the most potent compounds were tested against BACE1 and their neuroprotectivity on A beta-treated neurotoxicity in PC12 cells which depicted negligible activity. It should be noted that most of the synthesized compounds from both categories 5a-i and 5j-q showed a significant selectivity toward BChE. However, series 5j-q were more active toward AChE than series 5a-i.

  DOI：

  10.1016/j.bioorg.2019.103192