7-Phenylaminothieno[3,2-b]pyridine-6-carbonitrile 21

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 7-Phenylaminothieno[3,2-b]pyridine-6-carbonitrile 21
• 英文别名: 7-(2,4-dichloro-5-methoxyanilino)-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]phenyl]thieno[3,2-b]pyridine-6-carbonitrile
• 化学式: C₂₈H₂₇Cl₂N₅OS
• 分子量: 552.527
• InChiKey: REVUKULBOQJYPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对溴苯乙酸 在 4-二甲氨基吡啶 、 正丁基锂 、 硼酸三异丙酯 、 dimethyl sulfide borane 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 7-Phenylaminothieno[3,2-b]pyridine-6-carbonitrile 21
  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

文献信息

• Synthesis and Src Kinase Inhibitory Activity of 2-Phenyl- and 2-Thienyl-7-phenylaminothieno[3,2-<i>b</i>]pyridine-6-carbonitriles
  作者：Diane H. Boschelli、Biqi Wu、Ana Carolina Barrios Sosa、Haris Durutlic、Joan J. Chen、Yan Wang、Jennifer M. Golas、Judy Lucas、Frank Boschelli

  DOI：10.1021/jm050175p

  日期：2005.6.1

  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.