2-(2-Aminoethyl)-1,2,3,4-tetrahydroquinoline | 74274-06-9

• 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: 2-(2-Aminoethyl)-1,2,3,4-tetrahydroquinoline
• 英文别名: 2-(1,2,3,4-Tetrahydroquinolin-2-yl)ethan-1-amine；2-(1,2,3,4-tetrahydroquinolin-2-yl)ethanamine
• CAS: 74274-06-9
• 化学式: C₁₁H₁₆N₂
• mdl: MFCD13184136
• 分子量: 176.261
• InChiKey: UPALUOYFPHOBIF-UHFFFAOYSA-N

物化性质

• 沸点：
  145-147 °C(Press: 1 Torr)
• 密度：
  1.015±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-Aminoethyl)-1,2,3,4-tetrahydroquinoline 在 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.0h， 生成 N-[2-(1-benzyl-1,2,3,4-tetrahydroquinolin-2-yl)ethyl]propionamide
  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
• 作为产物：
  描述：

  2-(cyanomethyl)tetrahydroquinoline 在 氨 、 氢气 、 镍 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 60.0 ℃ 、405.33 kPa 条件下， 反应 6.0h， 生成 2-(2-Aminoethyl)-1,2,3,4-tetrahydroquinoline
  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

• [EN] 4- BROMO - 5 - (2- CHLORO - BENZOYLAMINO) - 1H - PYRAZOLE - 3 - CARBOXYLIC ACID AMIDE DERIVATIVES AND RELATED COMPOUNDS AS BRADYKININ B1 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] DERIVES AMIDES DE L'ACIDE CARBOXYLIQUE DE 4- BROMO - 5 - (2- CHLORO - BENZOYLAMINO) - 1H - PYRAZOLE 3 ET COMPOSES ASSOCIES EN TANT QU'ANTAGONISTES DE RECEPTEUR DE B1 DE LA BRADYKININE POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：ELAN PHARM INC

  公开号：WO2004098589A1

  公开（公告）日：2004-11-18

  Disclosed are compounds of formula I and II that are bradykinin B1 receptor antagonists and are useful for treating diseases, or relieving adverse symptoms associated with disease conditions, in mammals mediated by bradykinin B1 receptor. Certain of the compounds exhibit increased potency and are also expected to exhibit increased duration of action.

  公开的是化合物I和II的结构式，它们是激肽酶B1受体拮抗剂，适用于治疗哺乳动物中由激肽酶B1受体介导的疾病，或缓解与疾病状况相关的不良症状。其中某些化合物表现出增强的效力，并且预计还将表现出延长作用的特性。
• Scovill, John P.; Burckhalter, Joseph H., Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 23 - 27
  作者：Scovill, John P.、Burckhalter, Joseph H.

  DOI：——

  日期：——
• SCOVILL J. P.; BURKHALTER J. H., J. HETEROCYCL. CHEM., 1980, 17, NO 1, 23-27
  作者：SCOVILL J. P.、 BURKHALTER J. H.

  DOI：——

  日期：——
• 4- BROMO - 5 - (2- CHLORO - BENZOYLAMINO) - 1H - PYRAZOLE - 3 - CARBOXYLIC ACID AMIDE DERIVATIVES AND RELATED COMPOUNDS AS BRADYKININ B sb 1 /sb RECEPTOR ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY DISEASES
  申请人：ELAN PHARMACEUTICALS, INC.

  公开号：EP1633348A1

  公开（公告）日：2006-03-15
• 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.