7-chloro-1,4-dihydro-3(2H)-isoquinolinone | 113124-88-2

• 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: 7-chloro-1,4-dihydro-3(2H)-isoquinolinone
• 英文别名: 7-chloro-1,2,3,4-tetrahydroisoquinolin-3-one；7-Chloro-1,2-dihydroisoquinolin-3(4H)-one；7-chloro-2,4-dihydro-1H-isoquinolin-3-one
• CAS: 113124-88-2
• 化学式: C₉H₈ClNO
• 分子量: 181.622
• InChiKey: KVEBPBCIPKTOAR-UHFFFAOYSA-N

物化性质

• 沸点：
  399.6±42.0 °C(Predicted)
• 密度：
  1.290±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  7-chloro-1,4-dihydro-3(2H)-isoquinolinone 在 劳森试剂 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以47%的产率得到7-chloro-1,2,3,4-tetrahydroisoquinolin-3-thione
  参考文献：
  名称：

  “Methylene Bridge” to 5-HT₃ Receptor Antagonists: Conformationally Constrained Phenylguanidines

  摘要：

  Arylguanidines, depending upon their aromatic substitution pattern, display varying actions at 5-HT3 receptors (e.g., partial agonist, agonist, superagonist). Here, we demonstrate that conformational constraint of these agents as dihydroquinazolines (such as A6CDQ; 1) results in their conversion to 5-HT3 receptor antagonists. We examined the structure activity relationships of 1. Replacement/removal of any of the guanidinium nitrogen atoms of 1 resulted in decreased affinity. All three nitrogen atoms of 1 are necessary for optimal binding affinity at 5-HT3 receptors. Introduction of substituents as small as an N2-methyl group abolishes affinity. The results are consistent with homology modeling/docking studies and binding data from site-directed mutagenesis studies. Introducing a "methylene bridge" to the arylguanidine structure, regardless of its functional activity, results in a 5-HT3 receptor antagonist.

  DOI：

  10.1021/acschemneuro.8b00431
• 作为产物：
  描述：

  N,N'-methylenebis(4-chlorophenylacetamide) 在 焦磷酸 作用下， 反应 1.0h， 以87%的产率得到7-chloro-1,4-dihydro-3(2H)-isoquinolinone
  参考文献：
  名称：

  Studies on the Synthesis of Benzolactam Rings. II. Synthesis of 1,4-Dihydro-3(2H)-iaoquinolinone Derivatives

  摘要：

  DOI：

  10.3987/r-1987-09-2385

文献信息

• Studies on the Synthesis of Benzolactam Rings. II. Synthesis of 1,4-Dihydro-3(2H)-iaoquinolinone Derivatives
  作者：Yasuko Kamochi、Yasuo Watanabe

  DOI：10.3987/r-1987-09-2385

  日期：——
• “Methylene Bridge” to 5-HT₃ Receptor Antagonists: Conformationally Constrained Phenylguanidines
  作者：Ahmed S. Abdelkhalek、Genevieve S. Alley、Osama I. Alwassil、Shailesh Khatri、Philip D. Mosier、Heather L. Nyce、Michael M. White、Marvin K. Schulte、Małgorzata Dukat

  DOI：10.1021/acschemneuro.8b00431

  日期：2019.3.20

  Arylguanidines, depending upon their aromatic substitution pattern, display varying actions at 5-HT3 receptors (e.g., partial agonist, agonist, superagonist). Here, we demonstrate that conformational constraint of these agents as dihydroquinazolines (such as A6CDQ; 1) results in their conversion to 5-HT3 receptor antagonists. We examined the structure activity relationships of 1. Replacement/removal of any of the guanidinium nitrogen atoms of 1 resulted in decreased affinity. All three nitrogen atoms of 1 are necessary for optimal binding affinity at 5-HT3 receptors. Introduction of substituents as small as an N2-methyl group abolishes affinity. The results are consistent with homology modeling/docking studies and binding data from site-directed mutagenesis studies. Introducing a "methylene bridge" to the arylguanidine structure, regardless of its functional activity, results in a 5-HT3 receptor antagonist.