N'-[5-[[bis(prop-2-enyl)amino]methyl]thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide | 332361-12-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N'-[5-[[bis(prop-2-enyl)amino]methyl]thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide
• CAS: 332361-12-3
• 化学式: C₂₁H₂₅ClF₃N₅O₃S₂
• 分子量: 552.041
• InChiKey: QHPGSASRMDJEMF-UHFFFAOYSA-N

物化性质

• 密度：
  1.379±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N'-[5-[[bis(prop-2-enyl)amino]methyl]thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以50%的产率得到N'-[5-(aminomethyl)thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e
• 作为产物：
  描述：

  2,3-二氯-5-三氟甲基吡啶 在 吡啶 、 硫酸 、 一水合肼 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 9.5h， 生成 N'-[5-[[bis(prop-2-enyl)amino]methyl]thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e