(S)-(+)-2-ethyl-5-methoxy-3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole | 1012918-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-(+)-2-ethyl-5-methoxy-3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole
• 英文别名: 2-ethyl-5-methoxy-3-[[(2S)-1-methylpyrrolidin-2-yl]methyl]-1H-indole
• CAS: 1012918-27-2
• 化学式: C₁₇H₂₄N₂O
• 分子量: 272.39
• InChiKey: QTHPJXRRABGKDJ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  28.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  S-3-[[N-(benzyloxycarbonyl)pyrrolidin-2-yl]carbonyl]-2-ethyl-5-methoxy-1H-indole 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 (S)-(+)-2-ethyl-5-methoxy-3-[(1-methylpyrrolidin-2-yl)methyl]-1H-indole
  参考文献：
  名称：

  Binding of Serotonin and N₁-Benzenesulfonyltryptamine-Related Analogs at Human 5-HT₆ Serotonin Receptors: Receptor Modeling Studies

  摘要：

  A population of 100 graphics models of the human 5-HT6 serotonin receptor was constructed based on the structure of bovine rhodopsin. The endogenous tryptamine-based agonist serotonin (5-HT; 1) and the benzenesulfonyl-containing tryptamine-derived 5-HT6 receptor antagonist MS-245 (4a) were automatically docked with each of the 100 receptor models using a genetic algorithm approach. Similar studies were conducted with the more selective 5-HT6 receptor agonist EMDT (5) and optical isomers of EMDT-related analog 8, as well as with optical isomers of MS-245 (4a)-related and benzenesulfonyl-containing pyrrolidine 6 and aminotetralin 7. Although associated with the same general aromatic/hydrophobic binding cluster, 5-HT (1) and MS-245 (4a) were found to preferentially bind with distinct receptor conformations, and did so with different binding orientations (i.e., poses). A 5-HT pose/model was found to be common to EMDT (5) and its analogs, whereas that identified for MS-245 (4a) was found common to benzenesulfonyl-containing compounds. Specific amino acid residues were identified that can participate in binding, and evaluation of a sulfenamide analog of MS-245 indicates for the first time that the presence of the sulfonyl oxygen atoms enhances receptor affinity. The results indicate that the presence or absence of an N-1-benzenesulfonyl group is a major determinant of the manner in which tryptamine-related agents bind at 5-HT6 serotonin receptors.

  DOI：

  10.1021/jm070910s

文献信息

• Binding of Serotonin and N₁-Benzenesulfonyltryptamine-Related Analogs at Human 5-HT₆ Serotonin Receptors: Receptor Modeling Studies
  作者：Małgorzata Dukat、Philip D. Mosier、Renata Kolanos、Bryan L. Roth、Richard A. Glennon

  DOI：10.1021/jm070910s

  日期：2008.2.1

  A population of 100 graphics models of the human 5-HT6 serotonin receptor was constructed based on the structure of bovine rhodopsin. The endogenous tryptamine-based agonist serotonin (5-HT; 1) and the benzenesulfonyl-containing tryptamine-derived 5-HT6 receptor antagonist MS-245 (4a) were automatically docked with each of the 100 receptor models using a genetic algorithm approach. Similar studies were conducted with the more selective 5-HT6 receptor agonist EMDT (5) and optical isomers of EMDT-related analog 8, as well as with optical isomers of MS-245 (4a)-related and benzenesulfonyl-containing pyrrolidine 6 and aminotetralin 7. Although associated with the same general aromatic/hydrophobic binding cluster, 5-HT (1) and MS-245 (4a) were found to preferentially bind with distinct receptor conformations, and did so with different binding orientations (i.e., poses). A 5-HT pose/model was found to be common to EMDT (5) and its analogs, whereas that identified for MS-245 (4a) was found common to benzenesulfonyl-containing compounds. Specific amino acid residues were identified that can participate in binding, and evaluation of a sulfenamide analog of MS-245 indicates for the first time that the presence of the sulfonyl oxygen atoms enhances receptor affinity. The results indicate that the presence or absence of an N-1-benzenesulfonyl group is a major determinant of the manner in which tryptamine-related agents bind at 5-HT6 serotonin receptors.