4-(4-(3,4-dichlorophenyl)-5-mercapto-4H-1,2,4-triazol-3-yl)phenol | 1436433-85-0

• 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-(4-(3,4-dichlorophenyl)-5-mercapto-4H-1,2,4-triazol-3-yl)phenol
• CAS: 1436433-85-0
• 化学式: C₁₄H₉Cl₂N₃OS
• 分子量: 338.217
• InChiKey: ITLZLPFZUNLEEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.61
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.84
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(4-(3,4-dichlorophenyl)-5-mercapto-4H-1,2,4-triazol-3-yl)phenol 、 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-hydroxyphenyl)-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：

  3,4-dichloroaniline 在 potassium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.92h， 生成 4-(4-(3,4-dichlorophenyl)-5-mercapto-4H-1,2,4-triazol-3-yl)phenol
  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

• Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids
  作者：Tomasz Plech、Barbara Kaproń、Agata Paneth、Urszula Kosikowska、Anna Malm、Aleksandra Strzelczyk、Paweł Stączek、Łukasz Świątek、Barbara Rajtar、Małgorzata Polz-Dacewicz

  DOI：10.3390/molecules20046254

  日期：——

  We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.

  我们合成并研究了一系列 1,2,4-噁唑-环丙沙星杂合物的抗菌活性、毒性和对细菌II型拓扑异构酶的亲和力。这些化合物中有不少在抗击革兰氏阳性和革兰氏阴性细菌方面表现出比环丙沙星更强的活性。通过 MTT 试验评估得到的衍生物的毒性浓度远高于产生抗菌效果所需的浓度。最后，酶学研究结果表明，所分析的化合物在主要和次要分子靶标方面表现出与环丙沙星不同的偏好。