2-[(2,3-dihydro-1H-indol-1-yl)carbonyl]-5-methoxy-1H-indole | 1112054-52-0

• 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-[(2,3-dihydro-1H-indol-1-yl)carbonyl]-5-methoxy-1H-indole
• 英文别名: 2,3-dihydroindol-1-yl-(5-methoxy-1H-indol-2-yl)methanone
• CAS: 1112054-52-0
• 化学式: C₁₈H₁₆N₂O₂
• 分子量: 292.337
• InChiKey: LYAXYXQDFQWTJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(2,3-dihydro-1H-indol-1-yl)carbonyl]-5-methoxy-1H-indole 、 n,n-二甲基亚甲基碘化胺 以 氯仿 为溶剂， 反应 18.0h， 以79%的产率得到1-[2-(2,3-dihydro-1H-indol-1-yl-carbonyl)-5-methoxy-1H-indol-3-yl]-N,N-dimethylmethanamine
  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
• 作为产物：
  描述：

  吲哚啉 、 5-甲氧基吲哚-2-羧酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以87%的产率得到2-[(2,3-dihydro-1H-indol-1-yl)carbonyl]-5-methoxy-1H-indole
  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

• INDOLINES AND TETRAHYDRO-QUINOLINES AS PRODRUGS FOR TUMOUR TREATMENT
  申请人：THE SCHOOL OF PHARMACY, UNIVERSITY OF LONDON

  公开号：EP1408970A1

  公开（公告）日：2004-04-21
• [EN] INDOLINE AND TETRAHYDRO-QUINOLINES AS PRODRUGS FOR TUMOUR TREATMENT<br/>[FR] INDOLINE ET TETRAHYDRO-QUINOLINES COMME PROMEDICAMENTS DESTINES AU TRAITEMENT DE TUMEURS
  申请人：UNIV LONDON PHARMACY

  公开号：WO2002067937A1

  公开（公告）日：2002-09-06

  Compounds of the general formula I or IA or a salt in which X is H, Y is a leaving group, R1 preferably being an aromatic DNA binding subunit are prodrug analogues of duocarmycin. The compounds are expected to be hydroxylated at the carbon atom to which X is joined, by cytochrome P450, in particular by CYP1B1, expressed at high levels in tumours. The prodrug is expected to be activated preferentially in tumour cells, where it will act as a DNA alkylating agent preventing cell division.
• 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.