6-acetylamino-7-chloro-2-(5-methyl-1-triphenylmethylimidazol-4-ylmethyl)-1,2-dihydroisoquinolin-1-one | 142678-66-8

• 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: 6-acetylamino-7-chloro-2-(5-methyl-1-triphenylmethylimidazol-4-ylmethyl)-1,2-dihydroisoquinolin-1-one
• 英文别名: N-[7-chloro-2-[(5-methyl-1-tritylimidazol-4-yl)methyl]-1-oxoisoquinolin-6-yl]acetamide
• CAS: 142678-66-8
• 化学式: C₃₅H₂₉ClN₄O₂
• 分子量: 573.094
• InChiKey: OXAJDKRMLXUVGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetylamino-7-chloro-2-(5-methyl-1-triphenylmethylimidazol-4-ylmethyl)-1,2-dihydroisoquinolin-1-one 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 6-amino-7-chloro-1,2-dihydro-2-<<5(4)-methyl-4(5)-imidazolyl>methyl>-1-oxoisoquinoline dihydrochloride
  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：

  4-(氯甲基)-5-甲基-1-(三苯基甲基)-1H-咪唑 、 6-乙酰氨基-7-氯-1,2-二氢异喹啉-1-酮 以 dimethylformamide [DMF] 为溶剂， 生成 6-acetylamino-7-chloro-2-(5-methyl-1-triphenylmethylimidazol-4-ylmethyl)-1,2-dihydroisoquinolin-1-one
  参考文献：
  名称：

  Isoquinolinone derivative

  摘要：

  该式的异喹啉酮衍生物：其中R¹为氢、C1-4烷基、C1-4烷氧基或式：-NR⁴R⁵其中R⁴为氢、卤素、C1-4烷基或C2-4烷酰基，而R⁵为氢、C1-4烷基或苄基；R²为氢或C1-4烷基；R³为氢或C1-4烷基；l为1、2、3或4；m为1或2；n为1或2；---为单键或双键。其无毒酸加合物盐和水合物具有5-HT3受体的拮抗活性，可用于预防和/或治疗5-HT作用于5-HT3受体引起的疾病（特别是由抗癌剂给药引起的呕吐）。

  公开号：

  EP0482939A1

文献信息

• Isoquinolinone derivative
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0482939A1

  公开（公告）日：1992-04-29

  Isoquinolinone derivatives of the formula: wherein R¹ is hydrogen, C1-4 alkyl, C1-4 alkoxy or a group of formula:         -NR⁴R⁵ wherein R⁴ is hydrogen, halogen, C1-4 alkyl or C2-4 alkanoyl and R⁵ is hydrogen, C1-4 alkyl or benzyl; R² is hydrogen or C1-4 alkyl; R³ is hydrogen or C1-4 alkyl; l is 1, 2, 3 or 4; m is 1 or 2; n is 1 or 2 and --- is a single bond or double bond and non-toxic acid addition salts thereof and hydrates thereof possess an antagonistic activity against 5-HT3 receptor, and are useful for the prevention and/or treatment of diseases induced when 5-HT acts on 5-HT3 receptors (especially vomiting induced by the administration of an anti-cancer agent).

  该式的异喹啉酮衍生物：其中R¹为氢、C1-4烷基、C1-4烷氧基或式：-NR⁴R⁵其中R⁴为氢、卤素、C1-4烷基或C2-4烷酰基，而R⁵为氢、C1-4烷基或苄基；R²为氢或C1-4烷基；R³为氢或C1-4烷基；l为1、2、3或4；m为1或2；n为1或2；---为单键或双键。其无毒酸加合物盐和水合物具有5-HT3受体的拮抗活性，可用于预防和/或治疗5-HT作用于5-HT3受体引起的疾病（特别是由抗癌剂给药引起的呕吐）。
• 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.