2-(3-{2-[N-(tert-butoxycarbonyl)amino]ethyl}-1H-indol-5-yloxy)-N-(4-aminophenyl)acetamide | 162646-77-7

• 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-(3-{2-[N-(tert-butoxycarbonyl)amino]ethyl}-1H-indol-5-yloxy)-N-(4-aminophenyl)acetamide
• 英文别名: tert-butyl N-[2-[5-[2-(4-aminoanilino)-2-oxoethoxy]-1H-indol-3-yl]ethyl]carbamate
• CAS: 162646-77-7
• 化学式: C₂₃H₂₈N₄O₄
• 分子量: 424.5
• InChiKey: IPIQPNQLSSXSNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  119
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3-{2-[N-(tert-butoxycarbonyl)amino]ethyl}-1H-indol-5-yloxy)-N-(4-aminophenyl)acetamide 在 potassium carbonate 、 caesium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 丁酮 为溶剂， 生成 N-(4-{2-[3-(2-Amino-ethyl)-1H-indol-5-yloxy]-acetylamino}-phenyl)-2-[8-(4-methyl-piperazin-1-yl)-naphthalen-2-yloxy]-acetamide
  参考文献：
  名称：

  Dimers of 5HT 1 ligands preferentially bind to 5HT1b1d receptor subtypes

  摘要：

  New dimers of known 5HT(1) ligands (5HT, 1-NP or 8-OH-DPAT) have, been prepared and evaluated at human cloned 5HT(1B), 5HT(1D) and 5HT(1A) receptors. Binding experiments show that all these dimers have better affinities at 5HT(1B/1D) receptors than their corresponding monomeric ligands. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5HT(1B) receptor show that hetero-bivalent ligands [combining an agonist (5HT) with an antagonist (I-NP)] behave as partial agonists while the intrinsic activity of bivalent antagonists (combining two I-NP residues) was found to be spacer dependent. Surprisingly enough, the dimer of 8-OH-DPAT 6 binds to 5HT(1A), 5HT(1B) and 5HT(1D) receptors with similar high affinity, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00222-4
• 作为产物：
  描述：

  2-(3-{2-[N-(tert-butoxycarbonyl)amino]ethyl}-1H-indol-5-yloxy)-N-(4-nitrophenyl)acetamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以99%的产率得到2-(3-{2-[N-(tert-butoxycarbonyl)amino]ethyl}-1H-indol-5-yloxy)-N-(4-aminophenyl)acetamide
  参考文献：
  名称：

  Synthesis, binding affinity and intrinsic activity of new anilide derivatives of serotonin at human 5-HT1D receptors

  摘要：

  The design and synthesis of a new series of anilide derivatives of serotonin is described. Binding affinity and intrinsic activity were evaluated at cloned human 5-HT1D alpha, 5-HT1D beta and 5-HT1A receptors. Modification of the terminal substituent on the aromatic moiety (R(1)) was investigated and optimal affinity, activity and selectivity for 5-HT1D versus 5-HT1A receptors were obtained for the sulfonamide derivatives 9 and 10. Functional activity was also assessed in the New Zealand white rabbit saphenous vein contraction model, in which most of the compounds behaved as full agonists. Further structural modifications are also described, eg, replacement of the oxygen for carbon atom at the 5-position of the tryptamine moiety or terminal N-dimethylation.

  DOI：

  10.1016/s0223-5234(97)87539-3

文献信息

• Synthesis, binding affinity and intrinsic activity of new anilide derivatives of serotonin at human 5-HT1D receptors
  作者：M Perez、N Ayerbe、C Fourrier、I Sigogneau、PJ Pauwels、C Palmier、GW John、JP Valentin、S Halazy

  DOI：10.1016/s0223-5234(97)87539-3

  日期：1997.1

  The design and synthesis of a new series of anilide derivatives of serotonin is described. Binding affinity and intrinsic activity were evaluated at cloned human 5-HT1D alpha, 5-HT1D beta and 5-HT1A receptors. Modification of the terminal substituent on the aromatic moiety (R(1)) was investigated and optimal affinity, activity and selectivity for 5-HT1D versus 5-HT1A receptors were obtained for the sulfonamide derivatives 9 and 10. Functional activity was also assessed in the New Zealand white rabbit saphenous vein contraction model, in which most of the compounds behaved as full agonists. Further structural modifications are also described, eg, replacement of the oxygen for carbon atom at the 5-position of the tryptamine moiety or terminal N-dimethylation.
• Dimers of 5HT 1 ligands preferentially bind to 5HT1b1d receptor subtypes
  作者：Michel Perez、Catherine Jorand-Lebrun、Petrus J. Pauwels、Isabelle Pallard、Serge Halazy

  DOI：10.1016/s0960-894x(98)00222-4

  日期：1998.6

  New dimers of known 5HT(1) ligands (5HT, 1-NP or 8-OH-DPAT) have, been prepared and evaluated at human cloned 5HT(1B), 5HT(1D) and 5HT(1A) receptors. Binding experiments show that all these dimers have better affinities at 5HT(1B/1D) receptors than their corresponding monomeric ligands. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5HT(1B) receptor show that hetero-bivalent ligands [combining an agonist (5HT) with an antagonist (I-NP)] behave as partial agonists while the intrinsic activity of bivalent antagonists (combining two I-NP residues) was found to be spacer dependent. Surprisingly enough, the dimer of 8-OH-DPAT 6 binds to 5HT(1A), 5HT(1B) and 5HT(1D) receptors with similar high affinity, (C) 1998 Elsevier Science Ltd. All rights reserved.