2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindoline-1,3-dione | 1394868-09-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindoline-1,3-dione
• 英文别名: 2-[4-(Bromomethyl)-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindole-1,3-dione；2-[4-(bromomethyl)-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindole-1,3-dione
• CAS: 1394868-09-7
• 化学式: C₂₆H₁₄BrClFNO₃S
• 分子量: 554.823
• InChiKey: KKCIYTYTEXGYBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindoline-1,3-dione 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 {2-amino-4-[(4-(phenyl)piperazin-1-yl)methyl]-5-(4-fluorophenyl)thiophen-3-yl}-(4-chlorophenyl)methanone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-Amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-Modification on Allosteric Enhancer Activity at the A₁ Adenosine Receptor

  摘要：

  We have recently reported a detailed structure activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A(1) adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments.

  DOI：

  10.1021/jm3007504
• 作为产物：
  描述：

  4-氟苯硼酸 在 N-溴代丁二酰亚胺(NBS) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 cesium fluoride 、 过氧化苯甲酰 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 8.5h， 生成 2-[4-bromomethyl-3-(4-chlorobenzoyl)-5-(4-fluorophenyl)thiophen-2-yl]isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2-Amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-Modification on Allosteric Enhancer Activity at the A₁ Adenosine Receptor

  摘要：

  We have recently reported a detailed structure activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A(1) adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments.

  DOI：

  10.1021/jm3007504

文献信息

• Synthesis and biological evaluation of a new series of 2-amino-3-aroyl thiophene derivatives as agonist allosteric modulators of the A 1 adenosine receptor. A position-dependent effect study
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Carlota Lopez-Cara、Olga Cruz-Lopez、Allan R. Moorman、Arnault Massink、Adriaan P. IJzerman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1016/j.ejmech.2015.06.041

  日期：2015.8

  The 2-amino-3-(p-chlorobenzoyl)thiophene scaffold has been widely employed as a pharmacophore for the identification of small molecules acting as allosteric modulators at the adenosine A(1) receptor. A new series of 2-amino-3-(p-chlorobenzoyl)-4-benzy1-5-arylthiophene derivatives, characterized by the absence as well as the presence of electron-releasing or electron-withdrawing groups on the phenyl ring at the 4- and 5-positions of the thiophene ring, were identified as positive allosteric enhancers at the adenosine A1 receptor in binding (saturation, competition and dissociation kinetics) and functional assays. To better understand the positional requirements of substituents on the 2-amino-3-(p-chlorobenzoyl)thiophene core, the corresponding regioisomeric 4-aryl-5-benzylthiophene analogues were synthesized and found to possess reduced allosteric enhancer activity. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Synthesis and Biological Evaluation of 2-Amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-Modification on Allosteric Enhancer Activity at the A₁ Adenosine Receptor
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Olga Cruz-Lopez、Maria Kimatrai Salvador、Delia Preti、Mojgan Aghazadeh Tabrizi、Allan R. Moorman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1021/jm3007504

  日期：2012.9.13

  We have recently reported a detailed structure activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A(1) adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments.