2-(4-Methylpiperazin-1-yl)quinolin-4-amine | 1403606-41-6

• 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: 2-(4-Methylpiperazin-1-yl)quinolin-4-amine
• CAS: 1403606-41-6
• 化学式: C₁₄H₁₈N₄
• 分子量: 242.324
• InChiKey: GRQDDYOXJKSBNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  45.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 、 4-氨基-2-溴喹啉 以 四氢呋喃 为溶剂， 反应 1.5h， 以100 mg的产率得到2-(4-Methylpiperazin-1-yl)quinolin-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

• Quinoline compounds for use in mch receptor related disorders
  申请人：Frimurer Michael Thomas

  公开号：US20060111357A1

  公开（公告）日：2006-05-25

  The present invention relates to the use of quinoline compounds for the preparation of a pharmaceutical and/or a cosmetic composition for the treatment, prophylaxis and/or diagnosis of a condition caused by or involving a melanin-concentrating hormone. The invention also relates to novel quinoline compounds per se. The quinoline compounds have been found to interact with a melanin-concentrating hormone receptor, a MCH receptor. The compounds have modulating activity on the MCH receptor such as e.g. antagonistic, agonistic or allosteric activity and are useful for medicinal or cosmetic purposes such as, e.g. in the treatment or prevention of feeding disorders like obesity, metabolic syndrome, Type II diabetes, bulimia, etc. or in the treatment or prevention of depression.

  本发明涉及使用喹啉化合物制备用于治疗、预防和/或诊断由或涉及黑色素浓缩激素引起的疾病的药物和/或化妆品组合物。本发明还涉及新型喹啉化合物本身。已发现喹啉化合物与黑色素浓缩激素受体（MCH受体）相互作用。该化合物对MCH受体具有调节活性，例如拮抗、激动或异构活性，并可用于药用或化妆品用途，例如治疗或预防饮食障碍，如肥胖症、代谢综合征、2型糖尿病、贪食症等，或治疗或预防抑郁症。
• 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.