5-methoxy-2-methylindole-3-glyoxylamide | 124224-49-3

• 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: 5-methoxy-2-methylindole-3-glyoxylamide
• 英文别名: 2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetamide
• CAS: 124224-49-3
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: BHZSBKBTDTYQKI-UHFFFAOYSA-N

物化性质

• 沸点：
  488.2±55.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-methylindole-3-glyoxylamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 96.0h， 生成 5-methoxy-2-methyltryptamine
  参考文献：
  名称：

  5-HT1 and 5-HT2 binding profiles of the serotonergic agents .alpha.-methylserotonin and 2-methylserotonin

  摘要：

  alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT; 2) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT; 3) are considered to be 5-HT2-selective and 5-HT3-selective agents, respectively. These agents were synthesized and examined at serotonin (5-HT) binding sites because there is relatively little documentation as to their selectivity and because they have not been previously examined at the newly discovered 5-HT1D and 5-HT1E sites. As previously reported, 2-Me-5-HT possesses a low affinity (Ki greater than 500 nM) for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2 sites; this agent also displays a low affinity for 5-HT1D (Ki = 1220 nM) and 5-HT1E (Ki greater than 10,000 nM) sites. However, alpha-Me-5-HT displays little selectivity for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D sites (Ki = 42, 85, 150, and 150 nM, respectively) and a very low affinity for 5-HT1E (Ki greater than 10,000 nM) sites. Depending upon the radioligand used to label the sites, alpha-Me-5-HT displays either a low affinity (Ki = 880 nM with [3H]ketanserin) or a high affinity (Ki = 3 nM with [3H]DOB) for 5-HT2 sites. These results suggest that alpha-Me-5-HT is not as selective as previously considered and that caution should be used when employing this agent in pharmacological studies because it may act as mixed 5-HT1/5-HT2 agonist.

  DOI：

  10.1021/jm00164a046
• 作为产物：
  描述：

  methyl 2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetate 在 氨 作用下， 以 水 为溶剂， 反应 24.0h， 生成 5-methoxy-2-methylindole-3-glyoxylamide
  参考文献：
  名称：

  Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties

  摘要：

  A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl) amino]methyl}furan-2-yl)phenol (1, 5-HT6R K-i = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R K-j= 25, 5-HT2AR K-i = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with procognitive properties. (C) 2019 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111857

文献信息

• 5-HT1 and 5-HT2 binding profiles of the serotonergic agents .alpha.-methylserotonin and 2-methylserotonin
  作者：Abd M. Ismaiel、Milt Titeler、Keith J. Miller、Thomas S. Smith、Richard A. Glennon

  DOI：10.1021/jm00164a046

  日期：1990.2

  alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT; 2) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT; 3) are considered to be 5-HT2-selective and 5-HT3-selective agents, respectively. These agents were synthesized and examined at serotonin (5-HT) binding sites because there is relatively little documentation as to their selectivity and because they have not been previously examined at the newly discovered 5-HT1D and 5-HT1E sites. As previously reported, 2-Me-5-HT possesses a low affinity (Ki greater than 500 nM) for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2 sites; this agent also displays a low affinity for 5-HT1D (Ki = 1220 nM) and 5-HT1E (Ki greater than 10,000 nM) sites. However, alpha-Me-5-HT displays little selectivity for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D sites (Ki = 42, 85, 150, and 150 nM, respectively) and a very low affinity for 5-HT1E (Ki greater than 10,000 nM) sites. Depending upon the radioligand used to label the sites, alpha-Me-5-HT displays either a low affinity (Ki = 880 nM with [3H]ketanserin) or a high affinity (Ki = 3 nM with [3H]DOB) for 5-HT2 sites. These results suggest that alpha-Me-5-HT is not as selective as previously considered and that caution should be used when employing this agent in pharmacological studies because it may act as mixed 5-HT1/5-HT2 agonist.
• Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties
  作者：Jakub Staroń、Rafał Kurczab、Dawid Warszycki、Grzegorz Satała、Martyna Krawczyk、Ryszard Bugno、Tomasz Lenda、Piotr Popik、Adam S. Hogendorf、Agata Hogendorf、Krzysztof Dubiel、Mikołaj Matłoka、Rafał Moszczyński-Pętkowski、Jerzy Pieczykolan、Maciej Wieczorek、Paweł Zajdel、Andrzej J. Bojarski

  DOI：10.1016/j.ejmech.2019.111857

  日期：2020.1

  A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-[(2-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl) amino]methyl}furan-2-yl)phenol (1, 5-HT6R K-i = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-[(2-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R K-j= 25, 5-HT2AR K-i = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with procognitive properties. (C) 2019 The Authors. Published by Elsevier Masson SAS.