1-ethyl-3-[(5-methoxy-1,2,3,4-tetrahydroquinolin-2-yl)methyl]thiourea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-ethyl-3-[(5-methoxy-1,2,3,4-tetrahydroquinolin-2-yl)methyl]thiourea
• 英文别名: 1-Ethyl-3-[(5-methoxy-1,2,3,4-tetrahydroquinolin-2-yl)methyl]thiourea
• 化学式: C₁₄H₂₁N₃OS
• 分子量: 279.406
• InChiKey: WYVZXVQHHZOFGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-羟基-2-氰基喹啉 在 氨 、 氢气 、 镍 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 20.0~60.0 ℃ 、405.33 kPa 条件下， 反应 31.5h， 生成 1-ethyl-3-[(5-methoxy-1,2,3,4-tetrahydroquinolin-2-yl)methyl]thiourea
  参考文献：
  名称：

  Highly Potent and Selective MT₂ Melatonin Receptor Full Agonists from Conformational Analysis of 1-Benzyl-2-acylaminomethyl-tetrahydroquinolines

  摘要：

  Molecular superposition models guided the design of novel melatonin receptor ligands characterized by a 2-acylaminomethyltetrahydroquinoline scaffold. Starting from the structure of N-anilinoethylamide ligands, the flexible chain was conformationally constrained to reproduce the bioactive conformation of melatonin. Structure activity relationships were investigated, focusing on the substituent at the nitrogen atom, the position of the methoxy group, and the replacement of the amide side chain by urea and thiourea groups. The compounds were tested for binding affinity and intrinsic activity at human MT1, and MT2 receptors. Structural optimization resulted in N-[(1-benzyl-1,2,3,4-tetrahydro-5-methoxyquinolin-2-yl)methyl]propionamide (UCM1014), with picomolar MT2 binding affinity (K-i = 0.001 nM), more than 10000-fold selectivity over the MT1 receptor, and a full agonist profile (GTP gamma S test), being the most potent MT2-selective full agonist reported to date. Molecular dynamics simulations provided a rationale for high binding affinity, stereoselectivity, and agonist behavior of these novel melatonin receptor ligands based on superposition models and conformational preference.

  DOI：

  10.1021/acs.jmedchem.5b01066

文献信息

• Highly Potent and Selective MT₂ Melatonin Receptor Full Agonists from Conformational Analysis of 1-Benzyl-2-acylaminomethyl-tetrahydroquinolines
  作者：Gilberto Spadoni、Annalida Bedini、Simone Lucarini、Michele Mari、Daniel-Henri Caignard、Jean A. Boutin、Philippe Delagrange、Valeria Lucini、Francesco Scaglione、Alessio Lodola、Franca Zanardi、Daniele Pala、Marco Mor、Silvia Rivara

  DOI：10.1021/acs.jmedchem.5b01066

  日期：2015.9.24

  Molecular superposition models guided the design of novel melatonin receptor ligands characterized by a 2-acylaminomethyltetrahydroquinoline scaffold. Starting from the structure of N-anilinoethylamide ligands, the flexible chain was conformationally constrained to reproduce the bioactive conformation of melatonin. Structure activity relationships were investigated, focusing on the substituent at the nitrogen atom, the position of the methoxy group, and the replacement of the amide side chain by urea and thiourea groups. The compounds were tested for binding affinity and intrinsic activity at human MT1, and MT2 receptors. Structural optimization resulted in N-[(1-benzyl-1,2,3,4-tetrahydro-5-methoxyquinolin-2-yl)methyl]propionamide (UCM1014), with picomolar MT2 binding affinity (K-i = 0.001 nM), more than 10000-fold selectivity over the MT1 receptor, and a full agonist profile (GTP gamma S test), being the most potent MT2-selective full agonist reported to date. Molecular dynamics simulations provided a rationale for high binding affinity, stereoselectivity, and agonist behavior of these novel melatonin receptor ligands based on superposition models and conformational preference.