(2-amino-4-neopentyl-5-(2-(4-(n-pentyl)phenyl)ethynyl)thiophen-3-yl)(4-chlorophenyl)methanone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: (2-amino-4-neopentyl-5-(2-(4-(n-pentyl)phenyl)ethynyl)thiophen-3-yl)(4-chlorophenyl)methanone
• 英文别名: [2-Amino-4-(2,2-dimethylpropyl)-5-[2-(4-pentylphenyl)ethynyl]thiophen-3-yl]-(4-chlorophenyl)methanone；[2-amino-4-(2,2-dimethylpropyl)-5-[2-(4-pentylphenyl)ethynyl]thiophen-3-yl]-(4-chlorophenyl)methanone
• 化学式: C₂₉H₃₂ClNOS
• 分子量: 478.098
• InChiKey: QXUJIYJSKMBQLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-戊基苯乙炔 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 (2-amino-4-neopentyl-5-(2-(4-(n-pentyl)phenyl)ethynyl)thiophen-3-yl)(4-chlorophenyl)methanone
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm5008853

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.