2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetyl chloride | 1026388-93-1

• 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: 2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetyl chloride
• CAS: 1026388-93-1
• 化学式: C₁₂H₁₀ClNO₃
• 分子量: 251.669
• InChiKey: WFOKFPROUZEACN-UHFFFAOYSA-N

物化性质

• 熔点：
  131-133 °C (decomp)
• 沸点：
  460.5±55.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 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：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetyl chloride 在 ammonium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 104.0h， 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：

  5-甲氧基-2-甲基吲哚 、 草酰氯 以 乙醚 为溶剂， 以88%的产率得到2-(5-methoxy-2-methyl-1H-indol-3-yl)-2-oxoacetyl chloride
  参考文献：
  名称：

  生物学上重要的吲哚基喹喔啉的简便合成

  摘要：

  1,2-苯二胺与各种吲哚基醛的缩合，由相应的酰氯在 HSnBu3 存在下制备，提供 (1H-indol-3-yl) 喹喔啉。此外，在对位被强吸电子基团取代的 1,2-苯二胺提供 6-取代的 (1H-indol-3-yl) 喹喔啉。几种生物学上重要的喹喔啉以相同的方式制备。在所有情况下，产量都从好到极好。然而，被弱给电子甲基取代的 1,2-苯二胺得到 (1H-indol-3-yl)quinoxaline 的 6-甲基和 7-甲基异构体的不可分离的混合物。所有化合物均通过 1 H NMR、 13 C NMR 和 IR 光谱进行表征。

  DOI：

  10.3998/ark.5550190.0012.907

文献信息

• [EN] FAAH INHIBITORS<br/>[FR] INHIBITEURS DE FAAH
  申请人：IRONWOOD PHARMACEUTICALS INC

  公开号：WO2012088469A1

  公开（公告）日：2012-06-28

  The present disclosure relates to compounds useful as inhibitors of the enzyme Fatty Acid Amide Hydrolase (FAAH). The disclosure also provides pharmaceutically acceptable compositions comprising the compounds of the disclosure and methods of using the compositions in the treatment or prevention of various disorders. Compounds of the invention are described in Table 1.

  本公开涉及作为脂肪酰胺水解酶（FAAH）抑制剂有用的化合物。该公开还提供包括本公开化合物的药学上可接受的组合物，以及使用这些组合物在治疗或预防各种疾病中的方法。发明的化合物在表1中描述。
• Facile synthesis of biologically important indole based quinoxalines
  作者：Sukanta Kamila、Haribabu Ankati、Edward R. Biehl

  DOI：10.3998/ark.5550190.0012.907

  日期：——

  2-phenylenediamine with a variety of indole based aldehydes, prepared from the corresponding acid chloride in presence of HSnBu3, furnishes (1H-indol-3-yl)quinoxalines. In addition, 1,2-phenylenediamines substituted with a strong electron-withdrawing group at the para position, provides 6-substituted (1H-indol-3-yl)quinoxalines. Several biologically important quinoxalines were prepared in the same way. The

  1,2-苯二胺与各种吲哚基醛的缩合，由相应的酰氯在 HSnBu3 存在下制备，提供 (1H-indol-3-yl) 喹喔啉。此外，在对位被强吸电子基团取代的 1,2-苯二胺提供 6-取代的 (1H-indol-3-yl) 喹喔啉。几种生物学上重要的喹喔啉以相同的方式制备。在所有情况下，产量都从好到极好。然而，被弱给电子甲基取代的 1,2-苯二胺得到 (1H-indol-3-yl)quinoxaline 的 6-甲基和 7-甲基异构体的不可分离的混合物。所有化合物均通过 1 H NMR、 13 C NMR 和 IR 光谱进行表征。
• Copper(I)-Catalyzed Cascade Dearomatization of 2-Substituted Tryptophols with Arylidonium Salts
  作者：Chuan Liu、Wei Zhang、Li-Xin Dai、Shu-Li You

  DOI：10.1021/ol301939w

  日期：2012.9.7

  Copper(I)-catalyzed dearomative arylation and vinylation of 2-substituted tryptophols were realized with a subsequent cyclization reaction. The cascade dearomatization sequence provided versatile furoindoline derivatives with two quaternary carbon centers in good to excellent yields.

  在随后的环化反应中，实现了铜（I）催化的2-取代的三苯酚的脱芳基芳基化和乙烯基化。级联脱芳香化序列提供了具有两个季碳中心的多用途呋喃二氢吲哚衍生物，收率好至极好。
• Towards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties
  作者：Gilberto Spadoni、Annalida Bedini、Silvia Bartolucci、Daniele Pala、Marco Mor、Teresa Riccioni、Franco Borsini、Walter Cabri、Diana Celona、Mauro Marzi、Giorgio Tarzia、Silvia Rivara、Patrizia Minetti

  DOI：10.1016/j.ejmech.2014.04.034

  日期：2014.6

  Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, we explored the hypothesis that two such moieties can co-exist in the same ligand, binding to different pockets. We thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. We further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same molecule.
• Characterization of the 5-HT₇ Receptor. Determination of the Pharmacophore for 5-HT₇ Receptor Agonism and CoMFA-Based Modeling of the Agonist Binding Site
  作者：Erik S. Vermeulen、Anne W. Schmidt、Jeffrey S. Sprouse、Håkan V. Wikström、Cor J. Grol

  DOI：10.1021/jm030826m

  日期：2003.12.1

  On the basis of a set of 20 diverse 5-HT7 receptor agonists, the pharmacophore for 5-HT7 receptor agonism was determined. Additionally two CoMFA models were developed, based on different alignments of the agonists. Both models show good correlations between experimental and predictive pK(i) values and show a high degree of similarity. The CoMFA fields were subsequently used to map the agonist binding site of the model of the 5-HT7 receptor. Important roles in ligand binding are attributed to Asp162 of TM3 (interaction with a protonated nitrogen), and Thr244 of TM5 (interaction with a substituent at an aromatic moiety). Amino acid residues of the aromatic cluster of TM6 are hypothesized to play an important role in ligand binding as pi-pi stacking moieties. Agonists missing a hydrogen-bond-accepting moiety, but possessing an aromatic substituent instead, seem to bind the receptor with high affinity as well by occupying a lipophilic pocket hosted by residues of TM5 and TM6.