5-bromo-N-(5-(1-cyanocyclobutyl)-2-hydroxyphenyl)-2-hydroxybenzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-N-(5-(1-cyanocyclobutyl)-2-hydroxyphenyl)-2-hydroxybenzenesulfonamide
• 英文别名: 5-bromo-N-[5-(1-cyanocyclobutyl)-2-hydroxyphenyl]-2-hydroxybenzene-1-sulfonamide；5-bromo-N-[5-(1-cyanocyclobutyl)-2-hydroxyphenyl]-2-hydroxybenzenesulfonamide
• 化学式: C₁₇H₁₅BrN₂O₄S
• 分子量: 423.287
• InChiKey: DMCFTKWJTBOJFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对羟基苯乙腈 在 吡啶 、 硫酸 、 5%-palladium/activated carbon 、 氢气 、 硝酸 、 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 乙腈 、 mineral oil 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 50.0h， 生成 5-bromo-N-(5-(1-cyanocyclobutyl)-2-hydroxyphenyl)-2-hydroxybenzenesulfonamide
  参考文献：
  名称：

  Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5–MYC Protein–Protein Interaction

  摘要：

  The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small-molecule inhibitors of this interaction with potent in vitro binding affinity and report structurally related negative controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors and anticipate that the molecules disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.

  DOI：

  10.1021/acs.jmedchem.9b01411