4-(5-(1-(2-(benzo[d]thiazol-2-yl)hydrazono)ethyl)furan-2-yl)benzoic acid | 1445799-99-4

• 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: 4-(5-(1-(2-(benzo[d]thiazol-2-yl)hydrazono)ethyl)furan-2-yl)benzoic acid
• 英文别名: 4-[5-[N-(1,3-benzothiazol-2-ylamino)-C-methylcarbonimidoyl]furan-2-yl]benzoic acid
• CAS: 1445799-99-4
• 化学式: C₂₀H₁₅N₃O₃S
• 分子量: 377.423
• InChiKey: GRQTWRLIEGCBGG-UHFFFAOYSA-N

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：

  4-(5-acetylfuran-2-yl)benzoic acid 、 2-肼基苯并噻唑 以 乙醇 为溶剂， 以58%的产率得到4-(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

文献信息

• Discovery of Potent and Selective Benzothiazole Hydrazone Inhibitors of Bcl-X_L
  作者：Brad E. Sleebs、Wilhemus J. A. Kersten、Sanji Kulasegaram、George Nikolakopoulos、Effie Hatzis、Rebecca M. Moss、John P. Parisot、Hong Yang、Peter E. Czabotar、W. Douglas Fairlie、Erinna F. Lee、Jerry M. Adams、Lin Chen、Mark F. van Delft、Kym N. Lowes、Andrew Wei、David C.S. Huang、Peter M. Colman、Ian P. Street、Jonathan B. Baell、Keith Watson、Guillaume Lessene

  DOI：10.1021/jm400556w

  日期：2013.7.11

  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.