N-{4-[3-(Benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenyl}-2-[4-({4-[3-(benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenylcarbamoyl}-methyl)-piperazin-1-yl]-acetamide | 106191-50-8

• 英文名称: N-{4-[3-(Benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenyl}-2-[4-({4-[3-(benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenylcarbamoyl}-methyl)-piperazin-1-yl]-acetamide
• CAS: 106191-50-8；106191-52-0
• 化学式: C₄₆H₆₂N₆O₆
• 分子量: 795.035
• InChiKey: OAEFUUYSPRIPMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.18
• 重原子数：
  58.0
• 可旋转键数：
  22.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  130.08
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-{4-[3-(Benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenyl}-2-[4-({4-[3-(benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenylcarbamoyl}-methyl)-piperazin-1-yl]-acetamide 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以26%的产率得到N-[4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-2-(4-{[4-(2-hydroxy-3-isopropylamino-propoxy)-phenylcarbamoyl]-methyl}-piperazin-1-yl)-acetamide
  参考文献：
  名称：

  .beta.-Adrenoceptor antagonist activity of bivalent ligands. 1. Diamide analogs of practolol.

  摘要：

  Two series of bivalent ligands (P-X-P) containing the (R,S)-3-[(4-aminoaryl)oxy]-1-(isopropylamino)propan-2-ol pharmacophore and a connecting alpha,omega-dicarbonylpoly(methylene) [X = -OC(CH2)nCO-] or alpha,omega-N,N'-bis(carbonylmethylene) polymethylenediamine [X = -OCCH2NH(CH2)nNHCH2CO-] spanner were synthesized and evaluated for beta-adrenoceptor antagonist activity in rat heart and lung membrane preparations. The target compounds were obtained as a mixture of stereoisomers in modest yields by using a three to four step sequence beginning with N-benzylpractolol. The results from the competitive binding studies indicated that binding affinity increased by a factor of up to 160 by increasing the length of the group spanning the pharmacophore moieties. Modest increases in cardioselectivity were also obtained. The data suggest that further increases in spanner length and lipophilicity and optical resolution may improve the potential of a labeled bivalent beta 1-adrenoceptor antagonist to function as a myocardial imaging agent.

  DOI：

  10.1021/jm00387a025
• 作为产物：
  描述：

  3-[(对乙酰氨基)苯氧基]-1,2-环氧丙烷 在 盐酸 、 sodium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 甲醇 、 乙醚 、 乙醇 为溶剂， 反应 15.0h， 生成 N-{4-[3-(Benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenyl}-2-[4-({4-[3-(benzyl-isopropyl-amino)-2-hydroxy-propoxy]-phenylcarbamoyl}-methyl)-piperazin-1-yl]-acetamide
  参考文献：
  名称：

  .beta.-Adrenoceptor antagonist activity of bivalent ligands. 1. Diamide analogs of practolol.

  摘要：

  Two series of bivalent ligands (P-X-P) containing the (R,S)-3-[(4-aminoaryl)oxy]-1-(isopropylamino)propan-2-ol pharmacophore and a connecting alpha,omega-dicarbonylpoly(methylene) [X = -OC(CH2)nCO-] or alpha,omega-N,N'-bis(carbonylmethylene) polymethylenediamine [X = -OCCH2NH(CH2)nNHCH2CO-] spanner were synthesized and evaluated for beta-adrenoceptor antagonist activity in rat heart and lung membrane preparations. The target compounds were obtained as a mixture of stereoisomers in modest yields by using a three to four step sequence beginning with N-benzylpractolol. The results from the competitive binding studies indicated that binding affinity increased by a factor of up to 160 by increasing the length of the group spanning the pharmacophore moieties. Modest increases in cardioselectivity were also obtained. The data suggest that further increases in spanner length and lipophilicity and optical resolution may improve the potential of a labeled bivalent beta 1-adrenoceptor antagonist to function as a myocardial imaging agent.

  DOI：

  10.1021/jm00387a025