1,2-dihydro-5-methyl-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline | 133897-55-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1,2-dihydro-5-methyl-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline
• 英文别名: 5-methyl-2-[(5-methyl-1H-imidazol-4-yl)methyl]benzo[h]isoquinolin-1-one
• CAS: 133897-55-9
• 化学式: C₁₉H₁₇N₃O
• 分子量: 303.363
• InChiKey: KMBZUPVQJOKXHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  2

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 1,2-dihydro-5-methyl-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxobenzisoquinoline
  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 benzisoquinoline derivatives
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0405784A1

  公开（公告）日：1991-01-02

  Benzisoquinoline derivatives of the formula: wherein R¹ is hydrogen, C1-4 alkyl, C1-4 alkoxy, hydroxy or halogen; R³ is hydrogen or C1-4 alkyl; R⁴ is hydrogen or C1-6 alkyl; l is 1-6; m is 1 or 2: n is 1-3 and non-toxic acid addition salts or hydrates thereof possess antagonistic activity against 5-HT₃ receptor, and therefore are useful for the prevention and/or treatment of diseases which are induced when 5-HT acts on 5-HT₃ receptors (especially vomiting induced by the administration of anti-­cancer agents).

  式中的苯并异喹啉衍生物： 其中 R¹ 是氢、C1-4 烷基、C1-4 烷氧基、羟基或卤素； R³ 是氢或 C1-4 烷基 R⁴ 是氢或 C1-6 烷基； l 是 1-6； m 是 1 或 2： n 是 1-3 及其无毒酸加成盐或水合物具有拮抗 5-HT₃ 受体的活性，因此可用于预防和/或治疗 5-HT 作用于 5-HT₃ 受体时诱发的疾病（尤其是服用抗癌药物诱发的呕吐）。
• 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.