N-butyl-2-picolinoylhydrazinecarbothioamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-butyl-2-picolinoylhydrazinecarbothioamide
• 英文别名: 1-Butyl-3-(pyridine-2-carbonylamino)thiourea
• 化学式: C₁₁H₁₆N₄OS
• 分子量: 252.34
• InChiKey: HSQRSMNGUSTQHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  98.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-butyl-2-picolinoylhydrazinecarbothioamide 在 硫酸 作用下， 以 乙醇 为溶剂， 以29%的产率得到N-butyl-5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides

  摘要：

  Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer's disease, diabetic retinopathy, atherosclerosis, beta-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure-activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2 alpha and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.

  DOI：

  10.1007/s00044-019-02442-1
• 作为产物：
  描述：

  2-吡啶甲酸乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 N-butyl-2-picolinoylhydrazinecarbothioamide
  参考文献：
  名称：

  Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides

  摘要：

  Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer's disease, diabetic retinopathy, atherosclerosis, beta-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure-activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2 alpha and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.

  DOI：

  10.1007/s00044-019-02442-1

文献信息

• Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides
  作者：Hoon Choi、Wheesahng Yun、Jung-hun Lee、Seoul Jang、Sang Won Park、Dong Hwan Kim、Kyoung Pyo Seon、Jung-mi Hyun、Kwiwan Jeong、Jin-mo Ku、Tae-gyu Nam

  DOI：10.1007/s00044-019-02442-1

  日期：2019.12

  Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer's disease, diabetic retinopathy, atherosclerosis, beta-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure-activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2 alpha and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.