6-chloro-3,4-dihydroquinazoline

• 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: 6-chloro-3,4-dihydroquinazoline
• 英文别名: 6-Chloro-1,4-dihydroquinazoline；6-chloro-1,4-dihydroquinazoline
• 化学式: C₈H₇ClN₂
• 分子量: 166.61
• InChiKey: ZGVJZGFYCDEPOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  24.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-chloro-3,4-dihydroquinazoline 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以83%的产率得到6-chloro-3,4-dihydroquinazoline hydrochloride
  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：

  2-氨基-5-氯苯腈 在 lithium aluminium tetrahydride 、 硫酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6-chloro-3,4-dihydroquinazoline
  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

文献信息

• “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.