N-[4-[4-([2.2]paracyclophan-4-yl)piperazin-1-yl]butyl]benzo-[b]thiophenyl-2-carboxamide | 1250265-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[4-[4-([2.2]paracyclophan-4-yl)piperazin-1-yl]butyl]benzo-[b]thiophenyl-2-carboxamide
• 英文别名: N-[4-[4-(5-tricyclo[8.2.2.24,7]hexadeca-1(13),4,6,10(14),11,15-hexaenyl)piperazin-1-yl]butyl]-1-benzothiophene-2-carboxamide
• CAS: 1250265-86-1
• 化学式: C₃₃H₃₇N₃OS
• 分子量: 523.742
• InChiKey: HIGILHVUMICSAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯并噻吩-2-羧酸 、 4-[4-([2.2]paracyclophan-4-yl)piperazin-1-yl]butylamine 在 碳酸氢钠 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到N-[4-[4-([2.2]paracyclophan-4-yl)piperazin-1-yl]butyl]benzo-[b]thiophenyl-2-carboxamide
  参考文献：
  名称：

  Bioisosteric Replacement Leading to Biologically Active [2.2]Paracyclophanes with Altered Binding Profiles for Aminergic G-Protein-Coupled Receptors

  摘要：

  Exploring the chemical diversity space of GPCR ligands, we recently discovered [2.2]paracyclophanes as valuable atypical bioisosteres for secondary affinity and selectivity generating moieties. In find out if such an exchange also works for structural moieties that simulate the endogenous neurotransmitter, pi 1 or pi 2 or both systems pi 1 and pi 2 of three representative privileged structures of types 1, 2. and 3 were replaced by a [2.2]paracyclophane unit. Contributions of the respective functionalities to the binding at of a panel of relevant monoaminergic GPCRs were systematically examined. The study led to the paracyclophanylpiperazine 3a displaying excellent D-3 affinity (K-i = 1.6 nM) and a strongly attenuated binding to D-4, 5-HT1 and alpha(1). Whereas functional experiments showed neutral D-3 antagonist properties, mutagenesis studies indicated a binding mode that is similar to its lead compounds of type 3.

  DOI：

  10.1021/jm100899z

文献信息

• Bioisosteric Replacement Leading to Biologically Active [2.2]Paracyclophanes with Altered Binding Profiles for Aminergic G-Protein-Coupled Receptors
  作者：Marika Skultety、Harald Hübner、Stefan Löber、Peter Gmeiner

  DOI：10.1021/jm100899z

  日期：2010.10.14

  Exploring the chemical diversity space of GPCR ligands, we recently discovered [2.2]paracyclophanes as valuable atypical bioisosteres for secondary affinity and selectivity generating moieties. In find out if such an exchange also works for structural moieties that simulate the endogenous neurotransmitter, pi 1 or pi 2 or both systems pi 1 and pi 2 of three representative privileged structures of types 1, 2. and 3 were replaced by a [2.2]paracyclophane unit. Contributions of the respective functionalities to the binding at of a panel of relevant monoaminergic GPCRs were systematically examined. The study led to the paracyclophanylpiperazine 3a displaying excellent D-3 affinity (K-i = 1.6 nM) and a strongly attenuated binding to D-4, 5-HT1 and alpha(1). Whereas functional experiments showed neutral D-3 antagonist properties, mutagenesis studies indicated a binding mode that is similar to its lead compounds of type 3.