(2-amino-7-(trifluoromethyl)-8H-indeno[2,1-b]thiophen-3-yl)(4-chlorophenyl)methanone | 1245739-93-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-amino-7-(trifluoromethyl)-8H-indeno[2,1-b]thiophen-3-yl)(4-chlorophenyl)methanone
• 英文别名: [2-amino-5-(trifluoromethyl)-4H-indeno[2,1-b]thiophen-1-yl]-(4-chlorophenyl)methanone
• CAS: 1245739-93-8
• 化学式: C₁₉H₁₁ClF₃NOS
• 分子量: 393.817
• InChiKey: KVDMBLZANUOBIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)-1-茚酮 、 对氯苯乙酰腈 在 苯甲酸 、 β-丙氨酸 、 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以17%的产率得到(2-amino-7-(trifluoromethyl)-8H-indeno[2,1-b]thiophen-3-yl)(4-chlorophenyl)methanone
  参考文献：
  名称：

  Effects of Conformational Restriction of 2-Amino-3-benzoylthiophenes on A₁ Adenosine Receptor Modulation

  摘要：

  2-Amino-3-benzoylthiophenes (2A3BTs) have been widely reported to act as allosteric enhancers (A Es) at the A(1) adenosine receptor (A(1)AR). Herein we describe the synthesis of a series of 1-aminoindeno[1,2-c]thiophen-8-ones and a series of (2-aminoindeno[2,1-b]thiophen-3-yl)(phenyl)methanones as conformationally rigid analogues of the 2A3BTs. These compounds were screened using a functional assay of A(1)AR-mediated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in intact Chinese hamster ovary (CHO) cells to identify both potential agonistic effects as well as the ability to allosterically modulate the activity of the orthosteric agonist, N-6-(R-phenylisopropyl)adenosine (R-PIA). All of the 1-aminoindeno[1,2-c]thiophen-8-ones (14a-c and 17a-f) proved either to be inactive or behaved as antagonists in the functional assay. However, the (2-aminoindeno[2, 1-b]thiophen-3-yl)(phenyl)methanones with para-chloro substitution (compounds 25b, 25d, and 25f) did significantly augment the R-PIA response, indicating a positive allosteric effect.

  DOI：

  10.1021/jm1008538

文献信息

• Effects of Conformational Restriction of 2-Amino-3-benzoylthiophenes on A₁ Adenosine Receptor Modulation
  作者：Luigi Aurelio、Celine Valant、Bernard L. Flynn、Patrick M. Sexton、Jonathan M. White、Arthur Christopoulos、Peter J. Scammells

  DOI：10.1021/jm1008538

  日期：2010.9.23

  2-Amino-3-benzoylthiophenes (2A3BTs) have been widely reported to act as allosteric enhancers (A Es) at the A(1) adenosine receptor (A(1)AR). Herein we describe the synthesis of a series of 1-aminoindeno[1,2-c]thiophen-8-ones and a series of (2-aminoindeno[2,1-b]thiophen-3-yl)(phenyl)methanones as conformationally rigid analogues of the 2A3BTs. These compounds were screened using a functional assay of A(1)AR-mediated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in intact Chinese hamster ovary (CHO) cells to identify both potential agonistic effects as well as the ability to allosterically modulate the activity of the orthosteric agonist, N-6-(R-phenylisopropyl)adenosine (R-PIA). All of the 1-aminoindeno[1,2-c]thiophen-8-ones (14a-c and 17a-f) proved either to be inactive or behaved as antagonists in the functional assay. However, the (2-aminoindeno[2, 1-b]thiophen-3-yl)(phenyl)methanones with para-chloro substitution (compounds 25b, 25d, and 25f) did significantly augment the R-PIA response, indicating a positive allosteric effect.