7-(4-(3,5-dihydroxybenzyl)piperazin-1-yl)-1-(1-methyl-4,10-dihydrobenzo[b]pyrazolo[3,4-e][1,4]diazepin-5(1H)-yl)heptan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 7-(4-(3,5-dihydroxybenzyl)piperazin-1-yl)-1-(1-methyl-4,10-dihydrobenzo[b]pyrazolo[3,4-e][1,4]diazepin-5(1H)-yl)heptan-1-one
• 英文别名: 7-[4-[(3,5-Dihydroxyphenyl)methyl]piperazin-1-yl]-1-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)heptan-1-one；7-[4-[(3,5-dihydroxyphenyl)methyl]piperazin-1-yl]-1-(1-methyl-4,10-dihydropyrazolo[4,3-c][1,5]benzodiazepin-5-yl)heptan-1-one
• 化学式: C₂₉H₃₈N₆O₃
• 分子量: 518.659
• InChiKey: UUHHPKDLEFNZAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  97.1
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  7-溴庚酸 在 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 potassium iodide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 20.0h， 生成 7-(4-(3,5-dihydroxybenzyl)piperazin-1-yl)-1-(1-methyl-4,10-dihydrobenzo[b]pyrazolo[3,4-e][1,4]diazepin-5(1H)-yl)heptan-1-one
  参考文献：
  名称：

  Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1 a receptors

  摘要：

  A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V-1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY -267,464 had higher affinity for the V-1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V-1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V-1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V-1a receptor ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.050

文献信息

• Flexible analogues of WAY-267,464: Synthesis and pharmacology at the human oxytocin and vasopressin 1 a receptors
  作者：William T. Jorgensen、Damien W. Gulliver、Eryn L. Werry、Tristan Reekie、Mark Connor、Michael Kassiou

  DOI：10.1016/j.ejmech.2015.11.050

  日期：2016.1

  A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition radioligand binding assays at human oxytocin (OT) and arginine vasopressin 1a (V-1a) receptors. Physiological activity was determined using whole cell IP1 accumulation assays. Under these conditions, WAY -267,464 had higher affinity for the V-1a receptor compared to the OT receptor (8.5x more selective) with poor functional selectivity (2x selective for OT receptor agonism over V-1a receptor antagonism). Methylation of the resorcinol moiety (3) reversed the OT receptor pharmacological profile, removing agonist activity and inducing antagonist activity, without altering V-1a receptor pharmacology. All flexible tethered derivatives removed OT receptor affinity and activity resulting in the generation of highly selective V-1a receptor ligands. (C) 2015 Elsevier Masson SAS. All rights reserved.