7-[(2,4-dichloro-5-ethoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile | 855894-30-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 双噻吩和低聚噻吩
• 英文名称: 7-[(2,4-dichloro-5-ethoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile
• 英文别名: 7-(2,4-dichloro-5-ethoxyanilino)-2-(5-formylthiophen-3-yl)thieno[3,2-b]pyridine-6-carbonitrile
• CAS: 855894-30-3
• 化学式: C₂₁H₁₃Cl₂N₃O₂S₂
• 分子量: 474.391
• InChiKey: AJUVTWBJQLPHDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7-[(2,4-dichloro-5-ethoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile 、 N-甲基哌嗪 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以78%的产率得到7-(2,4-Dichloro-5-ethoxy-phenylamino)-2-[5-(4-methyl-piperazin-1-ylmethyl)-thiophen-3-yl]-thieno[3,2-b]pyridine-6-carbonitrile
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of 2-Phenyl- and 2-Thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles

  摘要：

  2-Phenyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles were recently reported to be inhibitors of Src kinase activity. In this study we present structure-activity relationships for additional thieno[3,2-b]pyridine-6-carbonitriles, modifying the substituents on the C-2 phenyl and C-7 phenylamino groups. Derivatives with various aminomethyl and aminoethyl substituents on the para position of the C-2 phenyl group retained the activity of the initial analogues. However, direct attachment of an amino group led to decreased activity. A 2,4-dichloro-5-methoxyphenylamino group at C-7 provided superior inhibition of Src enzymatic activity. Replacement of the C-2 phenyl group with a 3,5-substituted thiophene led to improved Src inhibitory activity compared to the parent compound, but other thiophene isomers were less active. One of the analogues reported here exhibited in vivo activity comparable to that of SKI-606, a related 3-quinolinecarbonitrile currently in clinical trials.

  DOI：

  10.1021/jm050175p
• 作为产物：
  描述：

  2,4-二氯-5-乙氧基苯胺 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 7-[(2,4-dichloro-5-ethoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile
  参考文献：
  名称：

  Synthesis and Src Kinase Inhibitory Activity of 2-Phenyl- and 2-Thienyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles

  摘要：

  2-Phenyl-7-phenylaminothieno[3,2-b]pyridine-6-carbonitriles were recently reported to be inhibitors of Src kinase activity. In this study we present structure-activity relationships for additional thieno[3,2-b]pyridine-6-carbonitriles, modifying the substituents on the C-2 phenyl and C-7 phenylamino groups. Derivatives with various aminomethyl and aminoethyl substituents on the para position of the C-2 phenyl group retained the activity of the initial analogues. However, direct attachment of an amino group led to decreased activity. A 2,4-dichloro-5-methoxyphenylamino group at C-7 provided superior inhibition of Src enzymatic activity. Replacement of the C-2 phenyl group with a 3,5-substituted thiophene led to improved Src inhibitory activity compared to the parent compound, but other thiophene isomers were less active. One of the analogues reported here exhibited in vivo activity comparable to that of SKI-606, a related 3-quinolinecarbonitrile currently in clinical trials.

  DOI：

  10.1021/jm050175p