(5-((2,4-dichlorophenyl)thio)-2,4-dihydroxyphenyl)(isoindolin-2-yl)methanone

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (5-((2,4-dichlorophenyl)thio)-2,4-dihydroxyphenyl)(isoindolin-2-yl)methanone
• 英文别名: [5-(2,4-Dichlorophenyl)sulfanyl-2,4-dihydroxyphenyl]-(1,3-dihydroisoindol-2-yl)methanone；[5-(2,4-dichlorophenyl)sulfanyl-2,4-dihydroxyphenyl]-(1,3-dihydroisoindol-2-yl)methanone
• 化学式: C₂₁H₁₅Cl₂NO₃S
• 分子量: 432.327
• InChiKey: RWYPSUVHSWQWRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  86.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以17 mg的产率得到(5-((2,4-dichlorophenyl)thio)-2,4-dihydroxyphenyl)(isoindolin-2-yl)methanone
  参考文献：
  名称：

  Resorcinol-Based Grp94-Selective Inhibitors

  摘要：

  Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum resident of the 90 kDa heat shock protein (Hsp90) family and represents a promising therapeutic target for the treatment of several diseases. Grp94 is the most unique member of the 90 kDa heat shock protein family due to a five amino acid insertion into its primary sequence, which creates hydrophobic subpockets exclusive to Grp94 that can be utilized for selective inhibition. The first resorcinol-based Grp94-selective inhibitor to take advantage of the hydrophobic S2 subpocket has been developed and shown to manifest low nanomolar affinity and similar to 10-fold selectivity for Grp94. Furthermore, these Grp94-selective inhibitors manifest low micromolar GI(50) values against multiple myeloma cells, supporting Grp94 as an emerging target for the treatment of this disease.

  DOI：

  10.1021/acsmedchemlett.7b00193

文献信息

• Resorcinol-Based Grp94-Selective Inhibitors
  作者：Anuj Khandelwal、Vincent M. Crowley、Brian S. J. Blagg

  DOI：10.1021/acsmedchemlett.7b00193

  日期：2017.10.12

  Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum resident of the 90 kDa heat shock protein (Hsp90) family and represents a promising therapeutic target for the treatment of several diseases. Grp94 is the most unique member of the 90 kDa heat shock protein family due to a five amino acid insertion into its primary sequence, which creates hydrophobic subpockets exclusive to Grp94 that can be utilized for selective inhibition. The first resorcinol-based Grp94-selective inhibitor to take advantage of the hydrophobic S2 subpocket has been developed and shown to manifest low nanomolar affinity and similar to 10-fold selectivity for Grp94. Furthermore, these Grp94-selective inhibitors manifest low micromolar GI(50) values against multiple myeloma cells, supporting Grp94 as an emerging target for the treatment of this disease.