N⁶-<4-(phenylsulfonyl)benzyl>-N⁶-methyl-2-(methylthio)-6-aminobenzindole | 138385-05-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N⁶-<4-(phenylsulfonyl)benzyl>-N⁶-methyl-2-(methylthio)-6-aminobenzindole
• 英文别名: N-[[4-(benzenesulfonyl)phenyl]methyl]-N-methyl-2-methylsulfanylbenzo[cd]indol-6-amine
• CAS: 138385-05-4
• 化学式: C₂₆H₂₂N₂O₂S₂
• 分子量: 458.605
• InChiKey: ZKNIDVMUAMMDSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.06
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.74
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N⁶-<4-(phenylsulfonyl)benzyl>-N⁶-methyl-2-(methylthio)-6-aminobenzindole 在 氨 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以87%的产率得到N⁶-methyl-N⁶-<<4-(phenylsulfonyl)phenyl>methyl>-6-aminobenzindole-2,6-diamine
  参考文献：
  名称：

  Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase

  摘要：

  The X-ray crystal-structure-based design, synthesis, and biological activity of a novel family of benz[cd]indole-containing inhibitors of thymidylate synthase (TS) are described. The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region. Combination of favored substituents for each region led to inhibitors with K(i)'s against the human enyzme in the range of 10-20 nM. Thymidine shift experiments suggested that the cytotoxic properties of the best enzyme inhibitors were due to TS targeting in cells. The inhibitors were synthesized from substitued 6-aminobenz[cd]indol-2(1H)-ones by alkylation with both a simple alkyl group and a substituted benzylic portion. The 2,6-diaminobenz[cd]indoles were prepared from the corresponding lactams by conversion to the thiolactam, alkylation to the methylated thiolactam, and then displacement with a substituted or unsubstituted amine.

  DOI：

  10.1021/jm00082a006
• 作为产物：
  描述：

  1-(苯磺酰基)-4-(溴甲基)苯 在 劳森试剂 、 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.5h， 生成 N⁶-<4-(phenylsulfonyl)benzyl>-N⁶-methyl-2-(methylthio)-6-aminobenzindole
  参考文献：
  名称：

  Crystal-structure-based design and synthesis of benz[cd]indole-containing inhibitors of thymidylate synthase

  摘要：

  The X-ray crystal-structure-based design, synthesis, and biological activity of a novel family of benz[cd]indole-containing inhibitors of thymidylate synthase (TS) are described. The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region. Combination of favored substituents for each region led to inhibitors with K(i)'s against the human enyzme in the range of 10-20 nM. Thymidine shift experiments suggested that the cytotoxic properties of the best enzyme inhibitors were due to TS targeting in cells. The inhibitors were synthesized from substitued 6-aminobenz[cd]indol-2(1H)-ones by alkylation with both a simple alkyl group and a substituted benzylic portion. The 2,6-diaminobenz[cd]indoles were prepared from the corresponding lactams by conversion to the thiolactam, alkylation to the methylated thiolactam, and then displacement with a substituted or unsubstituted amine.

  DOI：

  10.1021/jm00082a006