3,4-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-4-oxoquinazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3,4-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-4-oxoquinazoline
• 英文别名: 3-[(5-methyl-1H-imidazol-4-yl)methyl]quinazolin-4-one
• 化学式: C₁₃H₁₂N₄O
• 分子量: 240.264
• InChiKey: JHRLCGQLWWZOHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-羟基喹唑啉 、 5-(氯甲基)-4-甲基-1H-咪唑盐酸盐 在 sodium hydride 作用下， 生成 3,4-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-4-oxoquinazoline
  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.