2-{5-bromo-3-(4-chloro-benzoyl)-4-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-thiophen-2-yl}-isoindole-1,3-dione | 1059604-03-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-{5-bromo-3-(4-chloro-benzoyl)-4-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-thiophen-2-yl}-isoindole-1,3-dione
• 英文别名: 2-{5-bromo-3-(4-chlorobenzoyl)-4-[(4-(4-fluorophenyl)piperazin-1-yl)methyl]thiophen-2-yl}isoindoline-1,3-dione
• CAS: 1059604-03-3
• 化学式: C₃₀H₂₂BrClFN₃O₃S
• 分子量: 638.944
• InChiKey: VQCPFRMMDFELDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.66
• 重原子数：
  40.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  60.93
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-{5-bromo-3-(4-chloro-benzoyl)-4-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-thiophen-2-yl}-isoindole-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以52%的产率得到[2-Amino-5-bromo-4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]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-[5-bromo-4-bromomethyl-3-(4-chloro-benzoyl)-thiophen-2-yl]-isoindole-1,3-dione 、 1-(4-氟苯基)哌嗪 在 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以78%的产率得到2-{5-bromo-3-(4-chloro-benzoyl)-4-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-thiophen-2-yl}-isoindole-1,3-dione
  参考文献：
  名称：

  2-氨基-3-（4-氯苯甲酰基）-4- [N-（取代）哌嗪-1-基]噻吩作为A1腺苷受体有效变构增强剂的合成及生物学评估。

  摘要：

  描述了一系列2-氨基-3-（4-氯苯甲酰基）-4- [4-（烷基/芳基）哌嗪基-基]噻吩衍生物作为A 1-腺苷受体的变构增强剂的合成和评价。连接到哌嗪的苯环上取代基的性质似乎对变构增强剂活性产生根本影响，其中4-氯苯基8f和4-三氟甲基8j衍生物是结合中最活泼的化合物（饱和和置换实验）和功能性cAMP研究。

  DOI：

  10.1021/jm800586p

文献信息

• Synthesis and Biological Evaluation of Novel Allosteric Enhancers of the A₁ Adenosine Receptor Based on 2-Amino-3-(4′-Chlorobenzoyl)-4-Substituted-5-Arylethynyl Thiophene
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Adriaan P. IJzerman、Arnault Massink、Olga Cruz-Lopez、Luisa Carlota Lopez-Cara、Giulia Saponaro、Delia Preti、Mojgan Aghazadeh Tabrizi、Stefania Baraldi、Allan R. Moorman、Fabrizio Vincenzi、Pier Andrea Borea、Katia Varani

  DOI：10.1021/jm5008853

  日期：2014.9.25

  A Sonogashira coupling strategy was employed to synthesize a new series of allosteric modulators for the A(1) adenosine receptor based on the 2-amino-3-(p-chlorobenzoyl)-4-substituted thiophene skeleton, with a two-carbon (rigid or flexible) linker between the S-position of the thiophene ring and a (hetero)aryl or alkyl moiety. Among the compounds characterized by the presence of a common phenylacetylene moiety at the S-position of the thiophene ring, the neopentyl substitution at the 4-position supported a strong activity. In the series of 4-neopentyl derivatives, the presence of an acetylene spacer at the S-position of the thiophene is optimal for activity, whereas reduction of the acetylene to an ethyl moiety decreased activity, both in functional and binding assays. Derivatives 4e, 4g-h, 4j, 4l, and 4m were the most promising compounds in binding (saturation and competition) and functional cAMP studies, being able to potentiate agonist [H-3]CCPA binding to the A(1) receptor, with 4e as the best compound of the series. The latter compound also retarded the dissociation of another radiolabeled agonist, [H-3]NECA, from the receptor.