4-(3,4-dichlorophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol | 438031-65-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3,4-dichlorophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol
• 英文别名: 4-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-1H-1,2,4-triazole-5-thione
• CAS: 438031-65-3
• 化学式: C₁₅H₁₁Cl₂N₃OS
• mdl: MFCD03478376
• 分子量: 352.244
• InChiKey: JHEAMGYVAVJLSD-UHFFFAOYSA-N

物化性质

• 沸点：
  479.9±55.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.066
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3,4-dichlorophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol 、 溴乙酸 在 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 2-[[4-(3,4-Dichlorophenyl)-5-(4-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]acetic acid
  参考文献：
  名称：

  Discovery of Protein–Protein Interaction Inhibitors of Replication Protein A

  摘要：

  Replication protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity toward DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Toward this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RP inhibitors.

  DOI：

  10.1021/ml400032y
• 作为产物：
  描述：

  N-(3,4-dichlorophenyl)-2-(4-methoxybenzoyl)hydrazine-1-carbothioamide 在 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-(3,4-dichlorophenyl)-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol
  参考文献：
  名称：

  Discovery of Protein–Protein Interaction Inhibitors of Replication Protein A

  摘要：

  Replication protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity toward DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Toward this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RP inhibitors.

  DOI：

  10.1021/ml400032y

文献信息

• Discovery of Protein–Protein Interaction Inhibitors of Replication Protein A
  作者：James D. Patrone、J. Phillip Kennedy、Andreas O. Frank、Michael D. Feldkamp、Bhavatarini Vangamudi、Nicholas F. Pelz、Olivia W. Rossanese、Alex G. Waterson、Walter J. Chazin、Stephen W. Fesik

  DOI：10.1021/ml400032y

  日期：2013.7.11

  Replication protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity toward DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Toward this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RP inhibitors.