N-(4-hydroxybutyl)benzo[b]thiophene-2-carboxamide | 956585-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: N-(4-hydroxybutyl)benzo[b]thiophene-2-carboxamide
• 英文别名: benzothiophene-2-carboxylic acid (4-hydroxy-butyl)-amide；N-(4-hydroxybutyl)-1-benzothiophene-2-carboxamide
• CAS: 956585-62-9
• 化学式: C₁₃H₁₅NO₂S
• mdl: MFCD30294392
• 分子量: 249.334
• InChiKey: GIWKPWGRQRUBNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-hydroxybutyl)benzo[b]thiophene-2-carboxamide 、 地氯雷他定 在 N,N-二异丙基乙胺 作用下， 以 various solvent(s) 为溶剂， 反应 3.0h， 生成 N-[4-[4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]butyl]-1-benzothiophene-2-carboxamide
  参考文献：
  名称：

  Hybrid approach for the design of highly affine and selective dopamine D3 receptor ligands using privileged scaffolds of biogenic amine GPCR ligands

  摘要：

  A series of compounds containing privileged scaffolds of the known histamine H-1 receptor antagonists cetirizine, mianserin, ketotifen, loratadine, and bamipine were synthesized for further optimization as ligands for the related biogenic amine binding dopamine D-3 receptor. A pharmacological screening was carried out at dopamine D-2 and D-3 receptors. In the preliminary testing various ligands have shown moderate to high affinities for dopamine D-3 receptors, for example, N-(4-{4-[benzyl(phenyl)amino]piperidin-1-yl} butylnaphthalen-2-carboxamide (19a) (hD(3) K-i = 0.3 nM; hD(2) K-i = 703 nM), leading to a selectivity ratio of 2343. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.08.034
• 作为产物：
  描述：

  苯并噻吩-2-羧酸 、 4-氨基-1-丁醇 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以73%的产率得到N-(4-hydroxybutyl)benzo[b]thiophene-2-carboxamide
  参考文献：
  名称：

  Functionally Selective Dopamine D₂/D₃ Receptor Agonists Comprising an Enyne Moiety

  摘要：

  Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-2-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D-2L- and D-2S-mediated [S-35]GTP gamma S incorporation in the presence of coexpressed G alpha(o) and G alpha(i) subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-2S-promoted G(o) activation over G(i) coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G(o) activation than for G, coupling at the D-2L subtype. Functional selectivity for beta-arrestin recruitment over G(i) activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred beta-arrestin recruitment compared to G(o) coupling.

  DOI：

  10.1021/jm400520c

文献信息

• [EN] MEDICAMENTS<br/>[FR] MÉDICAMENTS
  申请人：MOTAC NEUROSCIENCE LTD

  公开号：WO2009056805A1

  公开（公告）日：2009-05-07

  A compound of formula (I) is described: wherein R1 and R2 are as defined in the text and wherein the compounds are intended for use in treating medical conditions characterized by an imbalance in dopamine receptor activity.

  描述了一种化合物的化学式(I)：其中R1和R2如文本中定义的那样，这些化合物旨在用于治疗以多巴胺受体活性失衡为特征的医疗状况。
• Medicaments
  申请人：Stark Holger

  公开号：US20110046153A1

  公开（公告）日：2011-02-24

  A compound of formal (I) is described: wherein R 1 and R 2 are as defined in the text and wherein the compounds are intended for use in treating medical conditions characterized by an imbalance in dopamine receptor activity.

  描述了一种正式化合物(I)：其中R1和R2如文本中所定义，并且这些化合物旨在用于治疗以多巴胺受体活性失衡为特征的医疗条件。
• [EN] TETRAHYDROBENZOTHIAZOLE DERIVATIVES WITH DOPAMINE RECEPTOR ACTIVITY<br/>[FR] MÉDICAMENTS
  申请人：MOTAC NEUROSCIENCE LTD

  公开号：WO2009056811A3

  公开（公告）日：2009-10-15
• Functionally Selective Dopamine D₂/D₃ Receptor Agonists Comprising an Enyne Moiety
  作者：Christine Hiller、Ralf C. Kling、Frank W. Heinemann、Karsten Meyer、Harald Hübner、Peter Gmeiner

  DOI：10.1021/jm400520c

  日期：2013.6.27

  Dopaminergics of types 1 and 2 incorporating a conjugated enyne as an atypical catechol-simulating moiety were synthesized in enantiomerically pure form and investigated for their metabolic stability. Radioligand binding studies indicated high affinity to D-2-like receptors. The test compounds were evaluated for their ability to differentially activate distinct signaling pathways. Measurement of D-2L- and D-2S-mediated [S-35]GTP gamma S incorporation in the presence of coexpressed G alpha(o) and G alpha(i) subunits showed significantly biased receptor activation for several test compounds. Thus, the 2-azaindolylcarboxamide (S)-2a exhibited substantial functional selectivity for D-2S-promoted G(o) activation over G(i) coupling. The most significant bias was determined for the triazolylalkoxy-substituted benzamide (S)-2c that displayed higher potency for G(o) activation than for G, coupling at the D-2L subtype. Functional selectivity for beta-arrestin recruitment over G(i) activation was observed for the biphenylcarboxamide (R)-1 and the 2-benzothiophenylcarboxamide (S)-2d, whereas the 2-substituted azaindole (S)-2a preferred beta-arrestin recruitment compared to G(o) coupling.
• Hybrid approach for the design of highly affine and selective dopamine D3 receptor ligands using privileged scaffolds of biogenic amine GPCR ligands
  作者：Britta C. Sasse、Ulrich R. Mach、Jukka Leppaenen、Thierry Calmels、Holger Stark

  DOI：10.1016/j.bmc.2007.08.034

  日期：2007.12

  A series of compounds containing privileged scaffolds of the known histamine H-1 receptor antagonists cetirizine, mianserin, ketotifen, loratadine, and bamipine were synthesized for further optimization as ligands for the related biogenic amine binding dopamine D-3 receptor. A pharmacological screening was carried out at dopamine D-2 and D-3 receptors. In the preliminary testing various ligands have shown moderate to high affinities for dopamine D-3 receptors, for example, N-(4-4-[benzyl(phenyl)amino]piperidin-1-yl} butylnaphthalen-2-carboxamide (19a) (hD(3) K-i = 0.3 nM; hD(2) K-i = 703 nM), leading to a selectivity ratio of 2343. (C) 2007 Elsevier Ltd. All rights reserved.