6-(4-(2-(benzothiazol-2-yl)hydrazono)-2,3-dihydro-1,1-dioxide-4H-1-benzothiopyran-4-yl)picolinic acid | 1135871-05-4

• 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)-2,3-dihydro-1,1-dioxide-4H-1-benzothiopyran-4-yl)picolinic acid
• 英文别名: 6-[4-(benzothiazol-2-yl-hydrazono)-2,3-dihydro-1,1-dioxido-benzothiopyran-6-yl]-pyridine-2-carboxylic acid；6-[4-(1,3-Benzothiazol-2-ylhydrazinylidene)-1,1-dioxo-2,3-dihydrothiochromen-6-yl]pyridine-2-carboxylic acid；6-[4-(1,3-benzothiazol-2-ylhydrazinylidene)-1,1-dioxo-2,3-dihydrothiochromen-6-yl]pyridine-2-carboxylic acid
• CAS: 1135871-05-4
• 化学式: C₂₂H₁₆N₄O₄S₂
• 分子量: 464.525
• InChiKey: YPKPNUQEDMJIGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 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：
  158
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl 6-(4-oxothiochroman-6-yl)picolinate 在 甲酸 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 6-(4-(2-(benzothiazol-2-yl)hydrazono)-2,3-dihydro-1,1-dioxide-4H-1-benzothiopyran-4-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

文献信息

• [EN] BENZOTHIAZOLE COMPOUNDS<br/>[FR] COMPOSÉS DE BENZOTHIAZOLE
  申请人：INST MEDICAL W & E HALL

  公开号：WO2009039553A1

  公开（公告）日：2009-04-02

  The present invention relates to benzothiazole compounds that mimic the activity of BH3 only proteins and are capable of binding to and neutralizing pro survival Bcl 2 proteins. The invention also relates to the use of such compounds in the regulation of cell death or cell survival and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death or cell survival.

  本发明涉及模拟BH3-only蛋白活性并能够结合和中和促生存Bcl-2蛋白的苯并噻唑化合物。该发明还涉及利用这类化合物调节细胞死亡或细胞存活，在治疗和/或预防与细胞死亡或细胞存活失调相关的疾病或病况。