5-morpholinomethyl-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole | 412043-47-1

• 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: 5-morpholinomethyl-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole
• 英文别名: 4-[[3-(1-benzyl-3,6-dihydro-2H-pyridin-4-yl)-1H-indol-5-yl]methyl]morpholine
• CAS: 412043-47-1
• 化学式: C₂₅H₂₉N₃O
• 分子量: 387.525
• InChiKey: CYWMIDIUHMZUJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  31.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-pentynoic chloride 、 5-morpholinomethyl-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 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 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 51.0h， 生成 5-morpholinomethyl-3-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-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

文献信息

• 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.