(4-methoxy-1-phenylsulfonyl-1H-indol-2-yl)-(1-phenylsulfonyl-1H-indol-2-yl)methanol | 896137-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-methoxy-1-phenylsulfonyl-1H-indol-2-yl)-(1-phenylsulfonyl-1H-indol-2-yl)methanol
• 英文别名: [1-(Benzenesulfonyl)indol-2-yl]-[1-(benzenesulfonyl)-4-methoxyindol-2-yl]methanol
• CAS: 896137-81-8
• 化学式: C₃₀H₂₄N₂O₆S₂
• 分子量: 572.662
• InChiKey: RKHGPRIKTIUZJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-methoxy-1-phenylsulfonyl-1H-indol-2-yl)-(1-phenylsulfonyl-1H-indol-2-yl)methanol 在 重铬酸吡啶 、 三氟乙酸吡啶 作用下， 以 二氯甲烷 为溶剂， 以58%的产率得到(1-phenylsulfonyl-1H-indol-2-yl)-(4-methoxy-1-phenylsulfonyl-1H-indol-2-yl)methanone
  参考文献：
  名称：

  Novel Bis(1H-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl) methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC50 values of 0.06 and 0.04 mu M, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40- fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

  DOI：

  10.1021/jm058033i
• 作为产物：
  描述：

  N-苯磺酸吲哚 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 为溶剂， 反应 3.0h， 生成 (4-methoxy-1-phenylsulfonyl-1H-indol-2-yl)-(1-phenylsulfonyl-1H-indol-2-yl)methanol
  参考文献：
  名称：

  Novel Bis(1H-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl) methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC50 values of 0.06 and 0.04 mu M, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40- fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.

  DOI：

  10.1021/jm058033i