methyl 3-[(dimethylamino)methyl]-5-methoxy-1H-indole-2-carboxylate | 99276-56-9

• 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: methyl 3-[(dimethylamino)methyl]-5-methoxy-1H-indole-2-carboxylate
• CAS: 99276-56-9
• 化学式: C₁₄H₁₈N₂O₃
• 分子量: 262.309
• InChiKey: MUHRMAIJYNTZKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-[(dimethylamino)methyl]-5-methoxy-1H-indole-2-carboxylate 生成 3-[(dimethylamino)methyl]-5-methoxy-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  TAKAMI, MASAAKI;OKADA, MASAFUMI;TSUDZII, NOBUDZI;XOSOGAI, TAKEHO;OMURA, S+

  摘要：

  DOI：
• 作为产物：
  描述：

  在 氨 作用下， 以 水 为溶剂， 生成 methyl 3-[(dimethylamino)methyl]-5-methoxy-1H-indole-2-carboxylate
  参考文献：
  名称：

  2-[(2,3-Dihydro-1H-indol-1-yl)methyl]melatonin Analogues: A Novel Class of MT₂-Selective Melatonin Receptor Antagonists

  摘要：

  A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT2 receptor accommodating the "out-of-plane" substituent of MT2-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety displayed an excellent binding affinity and selectivity toward the MT2-subtype (MT2, K-i = 1 nM; MT1, K-i = 115 nM), behaving as a competitive antagonist. 5-Me, 5-OMe, 5-Br, 6-NH2, and 6-NO2 substitution of the indoline moiety reduced both MT2 affinity and selectivity, indicating that hydrophobic interactions play a decisive role in binding the out-of-plane substituent. The cyclobutanecarboxamide (6e) showed a biphasic binding pattern at MT2 receptors, indicating the presence of two MT2 binding sites, a high affinity (K-i = 1 pM) and a low affinity (K-i = 148 nM), while MT1 binding affinity was very low (K-i = 1.4 mu M). Functional analysis of 6e revealed it to be an antagonist at MT1 receptors and a partial agonist, at best, at MT2 receptors.

  DOI：

  10.1021/jm800974d

文献信息

• Synthesis and pharmacological evaluation of 1,2,3,4-tetrahydropyrazino[1,2-a]indole and 2-[(phenylmethylamino)methyl]-1H-indole analogues as novel melatoninergic ligands
  作者：Christian Markl、Mohamed I. Attia、Justin Julius、Shalini Sethi、Paula A. Witt-Enderby、Darius P. Zlotos

  DOI：10.1016/j.bmc.2009.04.068

  日期：2009.7

  Two novel series of melatonin-derived compounds have been synthesized and pharmacologically evaluated at the MT1 and MT2 subtypes of melatonin receptors. Compounds 12b-c are non-selective high-affinity MT1 and MT2 receptor ligands (K-i = 7-11 nM). Compound 12b had little intrinsic activity at the MT1 receptor and no intrinsic activity at the MT2 receptor. Compound 20d displayed the highest MT2 binding affinity (K-i = 2 nM) and moderate selectivity toward the MT2 subtype (K-i MT1/MT2 ratio = 8) behaving as MT2 antagonist and MT1 agonist (IC50 = 112 pM). The findings help define SARs around the positions 1 and 2 of melatonin with respect to binding affinity, MT2 selectivity, and intrinsic activity. (C) 2009 Elsevier Ltd. All rights reserved.
• TAKAMI, MASAAKI;OKADA, MASAFUMI;TSUDZII, NOBUDZI;XOSOGAI, TAKEHO;OMURA, S+
  作者：TAKAMI, MASAAKI、OKADA, MASAFUMI、TSUDZII, NOBUDZI、XOSOGAI, TAKEHO、OMURA, S+

  DOI：——

  日期：——
• 2-[(2,3-Dihydro-1<i>H</i>-indol-1-yl)methyl]melatonin Analogues: A Novel Class of MT₂-Selective Melatonin Receptor Antagonists
  作者：Darius P. Zlotos、Mohamed I. Attia、Justin Julius、Shalini Sethi、Paula A. Witt-Enderby

  DOI：10.1021/jm800974d

  日期：2009.2.12

  A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT2 receptor accommodating the "out-of-plane" substituent of MT2-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety displayed an excellent binding affinity and selectivity toward the MT2-subtype (MT2, K-i = 1 nM; MT1, K-i = 115 nM), behaving as a competitive antagonist. 5-Me, 5-OMe, 5-Br, 6-NH2, and 6-NO2 substitution of the indoline moiety reduced both MT2 affinity and selectivity, indicating that hydrophobic interactions play a decisive role in binding the out-of-plane substituent. The cyclobutanecarboxamide (6e) showed a biphasic binding pattern at MT2 receptors, indicating the presence of two MT2 binding sites, a high affinity (K-i = 1 pM) and a low affinity (K-i = 148 nM), while MT1 binding affinity was very low (K-i = 1.4 mu M). Functional analysis of 6e revealed it to be an antagonist at MT1 receptors and a partial agonist, at best, at MT2 receptors.