2-[(5-Methyl-1-tritylimidazol-4-yl)methyl]-5-nitroisoquinolin-1-one | 143075-63-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 2-[(5-Methyl-1-tritylimidazol-4-yl)methyl]-5-nitroisoquinolin-1-one
• CAS: 143075-63-2
• 化学式: C₃₃H₂₆N₄O₃
• 分子量: 526.594
• InChiKey: HMCHESVEIAYZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(5-Methyl-1-tritylimidazol-4-yl)methyl]-5-nitroisoquinolin-1-one 在 palladium on activated charcoal 、 ammonium formate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以100%的产率得到5-Amino-2-[(5-methyl-1-tritylimidazol-4-yl)methyl]isoquinolin-1-one
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones

  摘要：

  Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopyridine moiety could be a good linking group because of its nicely planar structure. The steric limitations of the aromatic moiety were investigated by X-ray analysis and computer analysis and shown to be optimal when the aromatic moiety was constrained within an arched planar system, which could be successfully replaced by 3-(2-thienyl)-2-oxopyridine function or 6-amino-7-chloro-1-isoquinolinone function without any loss of the activity. Among the synthesized compounds, 42 showed the most potent activity in the inhibition of Bezold-Jarisch reflex in rats. Compounds 44a and 64 were orally active in the protection against cisplatin-induced emesis in dogs or ferrets. Structure-activity relationships are discussed.

  DOI：

  10.1021/jm00096a001
• 作为产物：
  描述：

  5-硝基-1H-异色烯-1-酮 在 氨 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 32.33h， 生成 2-[(5-Methyl-1-tritylimidazol-4-yl)methyl]-5-nitroisoquinolin-1-one
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones

  摘要：

  Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopyridine moiety could be a good linking group because of its nicely planar structure. The steric limitations of the aromatic moiety were investigated by X-ray analysis and computer analysis and shown to be optimal when the aromatic moiety was constrained within an arched planar system, which could be successfully replaced by 3-(2-thienyl)-2-oxopyridine function or 6-amino-7-chloro-1-isoquinolinone function without any loss of the activity. Among the synthesized compounds, 42 showed the most potent activity in the inhibition of Bezold-Jarisch reflex in rats. Compounds 44a and 64 were orally active in the protection against cisplatin-induced emesis in dogs or ferrets. Structure-activity relationships are discussed.

  DOI：

  10.1021/jm00096a001

文献信息

• Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones
  作者：Toshiaki Matsui、Tsuneyuki Sugiura、Hisao Nakai、Sadahiko Iguchi、Satoshi Shigeoka、Hideo Takada、Yoshihiko Odagaki、Yuhki Nagao、Yasuyuki Ushio

  DOI：10.1021/jm00096a001

  日期：1992.9

  Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopyridine moiety could be a good linking group because of its nicely planar structure. The steric limitations of the aromatic moiety were investigated by X-ray analysis and computer analysis and shown to be optimal when the aromatic moiety was constrained within an arched planar system, which could be successfully replaced by 3-(2-thienyl)-2-oxopyridine function or 6-amino-7-chloro-1-isoquinolinone function without any loss of the activity. Among the synthesized compounds, 42 showed the most potent activity in the inhibition of Bezold-Jarisch reflex in rats. Compounds 44a and 64 were orally active in the protection against cisplatin-induced emesis in dogs or ferrets. Structure-activity relationships are discussed.