3-(5-(1-(2-(benzo[d]thiazol-2-yl)hydrazono)ethyl)furan-2-yl)benzoic acid | 1135868-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-(5-(1-(2-(benzo[d]thiazol-2-yl)hydrazono)ethyl)furan-2-yl)benzoic acid
• 英文别名: 3-[5-[N-(1,3-benzothiazol-2-ylamino)-C-methylcarbonimidoyl]furan-2-yl]benzoic acid
• CAS: 1135868-78-8
• 化学式: C₂₀H₁₅N₃O₃S
• 分子量: 377.423
• InChiKey: VVEBCFHKQVSMJG-UHFFFAOYSA-N

物化性质

• 沸点：
  610.1±65.0 °C(predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.09
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  87.72
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  间氨基苯甲酸 在 盐酸 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 10.08h， 生成 3-(5-(1-(2-(benzo[d]thiazol-2-yl)hydrazono)ethyl)furan-2-yl)benzoic acid
  参考文献：
  名称：

  Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-X_L

  摘要：

  Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-X-L inhibitors originating from a high-throughput screening campaign. Small structural changes to the hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM). This molecular series exhibits drug-like characteristics, low molecular weights (M-w < 450) and unprecedented selectivity for Bcl-X-L. Surface plasmon resonance experiments afford strong evidence of binding affinity within the hydrophobic groove of Bcl-X-L. Biological experiments using engineered Mcl-1 deficient mouse embryonic fibroblasts (MEFs, reliant only on Bcl-X-L, for survival) and Bax/Bak deficient MEFs (insensitive to selective activation of Bcl-2-driven apoptosis) support a mechanism-based induction of apoptosis. This manuscript describes the first series of selective small-molecule inhibitors of Bcl-X-L and provides promising leads for the development of efficacious therapeutics against solid tumors and chemoresistant cancer cell lines.

  DOI：

  10.1021/jm400556w