5-(tert-butyldimethylsilanyloxy)-1-phenylsulfonyl-1H-indole | 896137-70-5

• 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: 5-(tert-butyldimethylsilanyloxy)-1-phenylsulfonyl-1H-indole
• 英文别名: 5-(tert-butyldimethylsilyloxy)-1-(phenylsulfonyl)-1H-indole；[1-(Benzenesulfonyl)indol-5-yl]oxy-tert-butyl-dimethylsilane
• CAS: 896137-70-5
• 化学式: C₂₀H₂₅NO₃SSi
• 分子量: 387.575
• InChiKey: VGRYBYYJNKLWRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.26
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(tert-butyldimethylsilanyloxy)-1-phenylsulfonyl-1H-indole 在 sodium hydroxide 、 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.0h， 生成 (4-Chloro-1H-indol-2-yl)-(5-hydroxy-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：

  5-苄氧基吲哚 在 palladium on activated charcoal ammonium formate 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 8.0h， 生成 5-(tert-butyldimethylsilanyloxy)-1-phenylsulfonyl-1H-indole
  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

文献信息

• Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones
  作者：Thomas Beckers、Andreas Sellmer、Emerich Eichhorn、Herwig Pongratz、Christoph Schächtele、Frank Totzke、Gerhard Kelter、Rebekka Krumbach、Heinz-Herbert Fiebig、Frank-D. Böhmer、Siavosh Mahboobi

  DOI：10.1016/j.bmc.2011.11.023

  日期：2012.1

  Several members of the quinazoline class of known tyrosine kinase inhibitors are approved anticancer agents, often showing selectivity for receptors of the HER/ErbB-family. Combining structural elements of this class with the bisindolylmethanone-structure led to a series of novel compounds. These compounds inhibited EGFR in the nanomolar range. Moreover, inhibition of EGFR autophosphorylation in intact A431 cells was shown, with IC50 values ranging form 0.3-1 mu M for compound 42, and 0.1-0.3 mu M for 45. In a panel of 42 human tumor cell lines the sensitivity profile of the novel compounds was shown to be similar to that of the quinazoline class of tyrosine kinase inhibitors lapatinib and erlotinib (Tarceva (R)). (C) 2011 Elsevier Ltd. All rights reserved.
• Novel Bis(1<i>H</i>-indol-2-yl)methanones as Potent Inhibitors of FLT3 and Platelet-Derived Growth Factor Receptor Tyrosine Kinase
  作者：Siavosh Mahboobi、Andrea Uecker、Andreas Sellmer、Christophe Cénac、Heymo Höcher、Herwig Pongratz、Emerich Eichhorn、Harald Hufsky、Antje Trümpler、Marit Sicker、Florian Heidel、Thomas Fischer、Carol Stocking、Sigurd Elz、Frank-D. Böhmer、Stefan Dove

  DOI：10.1021/jm058033i

  日期：2006.6.1

  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.