N-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-amine | 1225129-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-amine
• CAS: 1225129-87-2
• 化学式: C₁₄H₁₉N₅
• 分子量: 257.338
• InChiKey: VMMHKLBVXJNMEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,4-二氯喹唑啉 在 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 6.5h， 生成 N-methyl-2-(4-methylpiperazin-1-yl)quinazolin-4-amine
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of Highly Potent 5-HT₃ Receptor Ligands

  摘要：

  The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [H-3]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pK(i) > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.

  DOI：

  10.1021/jm300801u

文献信息

• Aminoquinoline Derivatives and Uses Thereof
  申请人：The McLean Hospital Corporation

  公开号：US20220008418A1

  公开（公告）日：2022-01-13

  Described herein are aminoquinoline and aminoacridine based hybrids, pharmaceutical compositions and medicaments that include such aminoquinoline and aminoacridine based hybrids, and methods of using such compounds for diagnosing and/or treating infections, neurodegerative diseases or disorders, inflammation, inflammation associated diseases and disorders, and/or diseases or disorders that are treatable with dopamine agonists such as the restless leg syndrome.
• US9567316B2
  申请人：——

  公开号：US9567316B2

  公开（公告）日：2017-02-14
• Design, Synthesis, and Structure–Activity Relationships of Highly Potent 5-HT₃ Receptor Ligands
  作者：Mark H. P. Verheij、Andrew J. Thompson、Jacqueline E. van Muijlwijk-Koezen、Sarah C. R. Lummis、Rob Leurs、Iwan J. P. de Esch

  DOI：10.1021/jm300801u

  日期：2012.10.25

  The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [H-3]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pK(i) > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand-receptor binding mode prediction using homology modeling and in silico docking approaches.