4-((1H-indol-5-yl)methyl)morpholine | 412043-48-2

• 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: 4-((1H-indol-5-yl)methyl)morpholine
• 英文别名: 4-(1H-indol-5-ylmethyl)morpholine
• CAS: 412043-48-2
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: HVUNVAQCFZYESC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  28.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-((1H-indol-5-yl)methyl)morpholine 在 sodium methylate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 51.0h， 生成 5-morpholinomethyl-1-(4-pentynoyl)-3-(1-benzyl-1,2,5,6-tetrahydropyridin-4-yl)indole
  参考文献：
  名称：

  Substituted Pentacyclic Carbazolones as Novel Muscarinic Allosteric Agents:  Synthesis and Structure−Affinity and Cooperativity Relationships

  摘要：

  Two series of pentacyclic carbazolones, 22 and 23, have been synthesized utilizing a facile intramolecular Diels-Alder reaction and are allosteric modulators at muscarinic acetylcholine receptors. Their affinities and cooperativities with acetylcholine and the antagonist N-methylscopolamine (NMS) at M-1-M-4 receptors have been analyzed and compared. All of the synthesized compounds are negatively cooperative with acetylcholine. In contrast, the majority of the compounds exhibit positive cooperativity with NMS, particularly at M-2 and M-4 receptors. The subtype selectivity, in terms of affinity, was in general M-2 > M-1 > M-4 > M-3. The largest increases in affinity produced by a single substitution of the core structure were given by the 1-OMe (22b) and 1-Cl (22d) derivatives. The position of the N in the ring did not appear to be important for binding affinity or cooperativity. Two compounds 22y and 23i, both trisubstituted analogues, were the most potent compounds synthesized, with dissociation constants of 30-100 nM for the M-2 NMS-liganded and unliganded receptor, respectively. The results indicate that the allosteric site, like the primary binding site, is capable of high-affinity interactions with molecules of relatively low molecular weight.

  DOI：

  10.1021/jm010946z
• 作为产物：
  描述：

  (1H-indol-5-yl)(morpholino)methanone 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以63%的产率得到4-((1H-indol-5-yl)methyl)morpholine
  参考文献：
  名称：

  Substituted Pentacyclic Carbazolones as Novel Muscarinic Allosteric Agents:  Synthesis and Structure−Affinity and Cooperativity Relationships

  摘要：

  Two series of pentacyclic carbazolones, 22 and 23, have been synthesized utilizing a facile intramolecular Diels-Alder reaction and are allosteric modulators at muscarinic acetylcholine receptors. Their affinities and cooperativities with acetylcholine and the antagonist N-methylscopolamine (NMS) at M-1-M-4 receptors have been analyzed and compared. All of the synthesized compounds are negatively cooperative with acetylcholine. In contrast, the majority of the compounds exhibit positive cooperativity with NMS, particularly at M-2 and M-4 receptors. The subtype selectivity, in terms of affinity, was in general M-2 > M-1 > M-4 > M-3. The largest increases in affinity produced by a single substitution of the core structure were given by the 1-OMe (22b) and 1-Cl (22d) derivatives. The position of the N in the ring did not appear to be important for binding affinity or cooperativity. Two compounds 22y and 23i, both trisubstituted analogues, were the most potent compounds synthesized, with dissociation constants of 30-100 nM for the M-2 NMS-liganded and unliganded receptor, respectively. The results indicate that the allosteric site, like the primary binding site, is capable of high-affinity interactions with molecules of relatively low molecular weight.

  DOI：

  10.1021/jm010946z

文献信息

• Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors
  作者：Giuseppe Giannini、Mauro Marzi、Maria Di Marzo、Gianfranco Battistuzzi、Riccardo Pezzi、Tiziana Brunetti、Walter Cabri、Loredana Vesci、Claudio Pisano

  DOI：10.1016/j.bmcl.2009.03.101

  日期：2009.5

  In order to gather further knowledge about the structural requirements on histone deacetylase inhibitors (HDACi), starting from the schematic model of the common pharmacophore that characterizes this class of molecules (surface recognition CAP group-connection unit-linker region-Zinc Binding Group), we designed and synthesized a series of hydroxamic acids containing a bis-(indolyl) methane moiety. HDAC inhibition pro. le and antiproliferative activity were evaluated. (C) 2009 Elsevier Ltd. All rights reserved.
• Substituted Pentacyclic Carbazolones as Novel Muscarinic Allosteric Agents:  Synthesis and Structure−Affinity and Cooperativity Relationships
  作者：Parviz Gharagozloo、Sebastian Lazareno、Masao Miyauchi、Angela Popham、Nigel J. M. Birdsall

  DOI：10.1021/jm010946z

  日期：2002.3.1

  Two series of pentacyclic carbazolones, 22 and 23, have been synthesized utilizing a facile intramolecular Diels-Alder reaction and are allosteric modulators at muscarinic acetylcholine receptors. Their affinities and cooperativities with acetylcholine and the antagonist N-methylscopolamine (NMS) at M-1-M-4 receptors have been analyzed and compared. All of the synthesized compounds are negatively cooperative with acetylcholine. In contrast, the majority of the compounds exhibit positive cooperativity with NMS, particularly at M-2 and M-4 receptors. The subtype selectivity, in terms of affinity, was in general M-2 > M-1 > M-4 > M-3. The largest increases in affinity produced by a single substitution of the core structure were given by the 1-OMe (22b) and 1-Cl (22d) derivatives. The position of the N in the ring did not appear to be important for binding affinity or cooperativity. Two compounds 22y and 23i, both trisubstituted analogues, were the most potent compounds synthesized, with dissociation constants of 30-100 nM for the M-2 NMS-liganded and unliganded receptor, respectively. The results indicate that the allosteric site, like the primary binding site, is capable of high-affinity interactions with molecules of relatively low molecular weight.