N,N-dimethyl-1,2-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline-5-carboxamide | 143074-96-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N,N-dimethyl-1,2-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline-5-carboxamide
• 英文别名: N,N-dimethyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1-oxobenzo[h]isoquinoline-5-carboxamide
• CAS: 143074-96-8
• 化学式: C₂₁H₂₀N₄O₂
• 分子量: 360.415
• InChiKey: TXOXPIWHAZEUDE-UHFFFAOYSA-N

物化性质

• 沸点：
  726.1±60.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-(氯甲基)-5-甲基-1-(三苯基甲基)-1H-咪唑 在 sodium hydride 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 14.33h， 生成 N,N-dimethyl-1,2-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline-5-carboxamide
  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.