3-[4-(4-phenylpiperazino)butyl ]indole-5-carboxylic acid | 689736-05-8

• 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: 3-[4-(4-phenylpiperazino)butyl ]indole-5-carboxylic acid
• 英文别名: 3-[4-(4-Phenyl-piperazin-1-yl)-butyl]-1H-indole-5-carboxylic acid；3-[4-(4-phenylpiperazin-1-yl)butyl]-1H-indole-5-carboxylic acid
• CAS: 689736-05-8
• 化学式: C₂₃H₂₇N₃O₂
• 分子量: 377.486
• InChiKey: XWAGQFOILGMJLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[4-(4-phenylpiperazino)butyl ]indole-5-carboxylic acid 、 N-甲基吗啉 、 叔丁胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以3-[4-(4-phenylpiperazino)butyl]indole-5-carboxylic acid N-tert-butylamide is obtained的产率得到3-[4-(4-phenylpiperazino)butyl]indole-5-carboxylic acid N-tert-butylamide
  参考文献：
  名称：

  Indole derivatives

  摘要：

  式I中的吲哚衍生物##STR1##其中Ind、Q和Ar的定义如此，以及它们的盐，在中枢神经系统上具有活性。

  公开号：

  US05418237A1
• 作为产物：
  描述：

  1-phenylpiperazine hydrochloride 在 sodium hydroxide 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 9.0h， 生成 3-[4-(4-phenylpiperazino)butyl ]indole-5-carboxylic acid
  参考文献：
  名称：

  Indolebutylamines as Selective 5-HT_1A Agonists

  摘要：

  A series of new 1-[4-(indol-3-yl)butyl]-4-arylpiperazines was prepared to identify highly selective and potent 5-HT1A agonists as potential pharmacological tools in studies of mood disorders. The combination of structural elements (indole-alkyl-amine and aryl-piperazine) known to introduce 5-HT1A receptor affinity and the proper selection of substituents (R on the indole moiety and R' on the aryl moiety) led to compounds with high receptor specificity and affinity. In particular, the introduction of the methyl ether or the unsubstituted carboxamide as substituents in position 5 of the indole (R) guaranteed serotonergic 5-HT1A affinity compared to the unsubstituted analogue. Para-substituted arylpiperazines (R') decreased dopaminergic D-2 binding and increased selectivity for the 5-HT1A receptor. Agonistic 5-HT1A receptor activity was confirmed in vivo in the ultrasonic vocalization test, and the results suggest that the introduction of the carboxamide residue leads to better bioavailability than the corresponding methyl ether. 3-{4-[4-(4-Carbamoylphenyl)piperazin-1-yl}butyl}-1H-indole-5-carboxamide 54 was identified as a highly selective 5-HT1A receptor agonist [GTPgammaS, ED50 = 4.7 nM] with nanomolar 5-HT1A affinity [IC50 = 0.9 nM] and selectivity [D-2, IC50 > 850 nM]. 3-{4-[4-(4-Methoxyphenyl)piperazin-1-yl]butyl}-1H-indole-5-carboxamide 45 is one of the most potent and selective 5-HT1A agonists known [5-HT1A, IC50 = 0.09 nM; D-2, IC50 = 140 nM].

  DOI：

  10.1021/jm040792y

文献信息

• Indole derivatives
  申请人：Merck Patent Gesellschaft mit Beschrankter Haftung

  公开号：US05418237A1

  公开（公告）日：1995-05-23

  Indole derivatives of formula I ##STR1## wherein Ind, Q and Ar are as defined herein, and their salts, are active on the central nervous system.

  式I中的吲哚衍生物##STR1##其中Ind、Q和Ar的定义如此，以及它们的盐，在中枢神经系统上具有活性。
• Indolderivate
  申请人：MERCK PATENT GmbH

  公开号：EP0496222B1

  公开（公告）日：1998-09-09
• US5418237A
  申请人：——

  公开号：US5418237A

  公开（公告）日：1995-05-23
• Indolebutylamines as Selective 5-HT_1A Agonists
  作者：Timo Heinrich、Henning Böttcher、Gerd D. Bartoszyk、Hartmut E. Greiner、Christoph A. Seyfried、Christoph van Amsterdam

  DOI：10.1021/jm040792y

  日期：2004.9.1

  A series of new 1-[4-(indol-3-yl)butyl]-4-arylpiperazines was prepared to identify highly selective and potent 5-HT1A agonists as potential pharmacological tools in studies of mood disorders. The combination of structural elements (indole-alkyl-amine and aryl-piperazine) known to introduce 5-HT1A receptor affinity and the proper selection of substituents (R on the indole moiety and R' on the aryl moiety) led to compounds with high receptor specificity and affinity. In particular, the introduction of the methyl ether or the unsubstituted carboxamide as substituents in position 5 of the indole (R) guaranteed serotonergic 5-HT1A affinity compared to the unsubstituted analogue. Para-substituted arylpiperazines (R') decreased dopaminergic D-2 binding and increased selectivity for the 5-HT1A receptor. Agonistic 5-HT1A receptor activity was confirmed in vivo in the ultrasonic vocalization test, and the results suggest that the introduction of the carboxamide residue leads to better bioavailability than the corresponding methyl ether. 3-4-[4-(4-Carbamoylphenyl)piperazin-1-yl}butyl}-1H-indole-5-carboxamide 54 was identified as a highly selective 5-HT1A receptor agonist [GTPgammaS, ED50 = 4.7 nM] with nanomolar 5-HT1A affinity [IC50 = 0.9 nM] and selectivity [D-2, IC50 > 850 nM]. 3-4-[4-(4-Methoxyphenyl)piperazin-1-yl]butyl}-1H-indole-5-carboxamide 45 is one of the most potent and selective 5-HT1A agonists known [5-HT1A, IC50 = 0.09 nM; D-2, IC50 = 140 nM].