4,4'-[octane-1,8-diylbis(1H-1,2,3-triazol-1,4-diylpropan-3,1-diyloxy)]bis[N-[4-[indan-2-yl(propyl)amino]butyl]-3-methoxybenzamide] | 1346263-85-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 4,4'-[octane-1,8-diylbis(1H-1,2,3-triazol-1,4-diylpropan-3,1-diyloxy)]bis[N-[4-[indan-2-yl(propyl)amino]butyl]-3-methoxybenzamide]
• 英文别名: N-[4-[2,3-dihydro-1H-inden-2-yl(propyl)amino]butyl]-4-[3-[1-[8-[4-[3-[4-[4-[2,3-dihydro-1H-inden-2-yl(propyl)amino]butylcarbamoyl]-2-methoxyphenoxy]propyl]triazol-1-yl]octyl]triazol-4-yl]propoxy]-3-methoxybenzamide
• CAS: 1346263-85-1
• 化学式: C₆₆H₉₂N₁₀O₆
• 分子量: 1121.52
• InChiKey: KBPAXMUQBHLMMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.1
• 重原子数：
  82
• 可旋转键数：
  39
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1,8-diazidooctane 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.17h， 生成 4,4'-[octane-1,8-diylbis(1H-1,2,3-triazol-1,4-diylpropan-3,1-diyloxy)]bis[N-[4-[indan-2-yl(propyl)amino]butyl]-3-methoxybenzamide]
  参考文献：
  名称：

  Development of a Bivalent Dopamine D₂ Receptor Agonist

  摘要：

  Bivalent D-2 agonists may function as useful molecular probes for the discovery of novel neurological therapeutics. On the basis of our recently developed bivalent dopamine D-2 receptor antagonists of type 1, the bivalent agonist 2 was synthesized when a spacer built from 22 atoms was employed. Compared to the monovalent control compound 6 containing a capped spacer, the bis-aminoindane derivative 2 revealed substantial steepening of the competition curve, indicating a bivalent binding mode. Dimer-specific Hill slopes were not a result of varying functional properties because both the dopaminergic 2 and the monovalent control agent 6 proved to be D-2 agonists substantially inhibiting cAMP accumulation and inducing D-2 receptor internalization. Investigation of the heterobivalent ligands 8 and 9, containing an agonist and a phenylpiperazine-based antagonist pharmacophore, revealed moderate steepening of the displacement curves and antagonist to very weak partial agonist properties.

  DOI：

  10.1021/jm2009919

文献信息

• Development of a Bivalent Dopamine D₂ Receptor Agonist
  作者：Julia Kühhorn、Angela Götz、Harald Hübner、Dawn Thompson、Jennifer Whistler、Peter Gmeiner

  DOI：10.1021/jm2009919

  日期：2011.11.24

  Bivalent D-2 agonists may function as useful molecular probes for the discovery of novel neurological therapeutics. On the basis of our recently developed bivalent dopamine D-2 receptor antagonists of type 1, the bivalent agonist 2 was synthesized when a spacer built from 22 atoms was employed. Compared to the monovalent control compound 6 containing a capped spacer, the bis-aminoindane derivative 2 revealed substantial steepening of the competition curve, indicating a bivalent binding mode. Dimer-specific Hill slopes were not a result of varying functional properties because both the dopaminergic 2 and the monovalent control agent 6 proved to be D-2 agonists substantially inhibiting cAMP accumulation and inducing D-2 receptor internalization. Investigation of the heterobivalent ligands 8 and 9, containing an agonist and a phenylpiperazine-based antagonist pharmacophore, revealed moderate steepening of the displacement curves and antagonist to very weak partial agonist properties.