2-[5-(4-fluorophenyl)-3-(4-chlorobenzoyl)-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindoline-1,3-dione | 1394867-95-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[5-(4-fluorophenyl)-3-(4-chlorobenzoyl)-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindoline-1,3-dione
• 英文别名: 2-[3-(4-Chlorobenzoyl)-5-(4-fluorophenyl)-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindole-1,3-dione；2-[3-(4-chlorobenzoyl)-5-(4-fluorophenyl)-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindole-1,3-dione
• CAS: 1394867-95-8
• 化学式: C₃₆H₂₇ClFN₃O₃S
• 分子量: 636.146
• InChiKey: BMCUBLSZVRYXOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  89.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[5-(4-fluorophenyl)-3-(4-chlorobenzoyl)-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-2-yl]isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以53%的产率得到{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：

  2-[3-(4-chlorobenzoyl)-5-bromo-4-methylthiophen-2-yl]isoindoline-1,3-dione 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 、 三乙胺 、 cesium fluoride 、 过氧化苯甲酰 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 11.5h， 生成 2-[5-(4-fluorophenyl)-3-(4-chlorobenzoyl)-4-[(4-phenylpiperazin-1-yl)methyl]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