(3-Thien-2-yl-1,2,4-oxadiazol-5-yl)acetonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (3-Thien-2-yl-1,2,4-oxadiazol-5-yl)acetonitrile
• 英文别名: 2-(3-thiophen-2-yl-1,2,4-oxadiazol-5-yl)acetonitrile
• 化学式: C₈H₅N₃OS
• mdl: MFCD06655310
• 分子量: 191.213
• InChiKey: MIGCJTAXTSPMND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  91
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-Thien-2-yl-1,2,4-oxadiazol-5-yl)acetonitrile 、 3-azidobenzyl alcohol 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 (3-(5-amino-4-(3-(thiophen-2-yl)-1,2,4-oxadiazol-5-yl)-1H-1,2,3-triazol-1-yl)phenyl)methanol
  参考文献：
  名称：

  Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan

  摘要：

  Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving chemoresistance in cancers such as renal cell carcinoma (RCC). Using a cell-based luciferase reporter assay to screen small molecules, we identified a novel inhibitor of miR-21 function. Following structure-activity relationship studies, an optimized lead compound demonstrated cytotoxicity in several cancer cell lines. In a chemoresistant-RCC cell line, inhibition of miR-21 via small molecule treatment rescued the expression of tumor-suppressor proteins and sensitized cells to topotecan-induced apoptosis. This resulted in a > 10-fold improvement in topotecan activity in cell viability and clonogenic assays. Overall, this work reports a novel small molecule inhibitor for perturbing miR-21 function and demonstrates an approach to enhancing the potency of chemotherapeutics specifically for cancers derived from oncomir addiction.

  DOI：

  10.1021/acs.jmedchem.7b01891
• 作为产物：
  描述：

  2-氰基噻吩 在 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 (3-Thien-2-yl-1,2,4-oxadiazol-5-yl)acetonitrile
  参考文献：
  名称：

  Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan

  摘要：

  Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving chemoresistance in cancers such as renal cell carcinoma (RCC). Using a cell-based luciferase reporter assay to screen small molecules, we identified a novel inhibitor of miR-21 function. Following structure-activity relationship studies, an optimized lead compound demonstrated cytotoxicity in several cancer cell lines. In a chemoresistant-RCC cell line, inhibition of miR-21 via small molecule treatment rescued the expression of tumor-suppressor proteins and sensitized cells to topotecan-induced apoptosis. This resulted in a > 10-fold improvement in topotecan activity in cell viability and clonogenic assays. Overall, this work reports a novel small molecule inhibitor for perturbing miR-21 function and demonstrates an approach to enhancing the potency of chemotherapeutics specifically for cancers derived from oncomir addiction.

  DOI：

  10.1021/acs.jmedchem.7b01891