6-(4-(2-(benzothiazol-2-yl)hydrazono)thiochroman-6-yl)picolinic acid | 1135871-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 6-(4-(2-(benzothiazol-2-yl)hydrazono)thiochroman-6-yl)picolinic acid
• 英文别名: 6-[4-(benzothiazol-2-yl-hydrazono)-2,3-dihydro-benzothiopyran-6-yl]-pyridine-2-carboxylic acid；6-[4-(1,3-Benzothiazol-2-ylhydrazinylidene)-2,3-dihydrothiochromen-6-yl]pyridine-2-carboxylic acid；6-[4-(1,3-benzothiazol-2-ylhydrazinylidene)-2,3-dihydrothiochromen-6-yl]pyridine-2-carboxylic acid
• CAS: 1135871-01-0
• 化学式: C₂₂H₁₆N₄O₂S₂
• 分子量: 432.527
• InChiKey: ZCEFNUPJBUDIPI-UHFFFAOYSA-N

物化性质

• 沸点：
  701.3±70.0 °C(predicted)
• 密度：
  1.51±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiochroman-4-one 在 bis-triphenylphosphine-palladium(II) chloride 、 四丁基溴化铵 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成 6-(4-(2-(benzothiazol-2-yl)hydrazono)thiochroman-6-yl)picolinic 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