2-{1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-1H-indazol-3-yl}-acetamide | 436161-16-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 2-{1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-1H-indazol-3-yl}-acetamide
• 英文别名: 2-[1-[3-[Tert-butyl(dimethyl)silyl]oxypropyl]indazol-3-yl]acetamide
• CAS: 436161-16-9
• 化学式: C₁₈H₂₉N₃O₂Si
• 分子量: 347.533
• InChiKey: RAWVGYFMGUAQMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-{1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-1H-indazol-3-yl}-acetamide 在 吡啶 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.67h， 生成 3-[1-[3-[(methylsulfonyl)oxy]propyl]-1H-indazol-3-yl]-4-[1-(2-naphthalenyl)-1H-indol-3-yl]-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β:  Synthesis, Biological Activity, and Cardiovascular Safety

  摘要：

  Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3 beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-beta II (IC50 = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.

  DOI：

  10.1021/jm049478u
• 作为产物：
  描述：

  吲唑-3-乙酸 在 1-羟基苯并三唑 、 caesium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-{1-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-1H-indazol-3-yl}-acetamide
  参考文献：
  名称：

  Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β:  Synthesis, Biological Activity, and Cardiovascular Safety

  摘要：

  Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3 beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-beta II (IC50 = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.

  DOI：

  10.1021/jm049478u

文献信息

• [EN] SUBSTITUTED PYRROLINES AS KINASE INHIBITORS<br/>[FR] PYRROLINES SUBSTITUEES EN TANT QU'INHIBITEURS DE KINASE
  申请人：——

  公开号：WO2003103663A3

  公开（公告）日：2004-07-08
• Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β:  Synthesis, Biological Activity, and Cardiovascular Safety
  作者：Han-Cheng Zhang、Claudia K. Derian、David F. McComsey、Kimberly B. White、Hong Ye、Leonard R. Hecker、Jian Li、Michael F. Addo、Diane Croll、Annette J. Eckardt、Charles E. Smith、Quan Li、Wai-Man Cheung、Bruce R. Conway、Stuart Emanuel、Keith T. Demarest、Patricia Andrade-Gordon、Bruce P. Damiano、Bruce E. Maryanoff

  DOI：10.1021/jm049478u

  日期：2005.3.1

  Novel indolylindazolylmaleimides were synthesized and examined for kinase inhibition. We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC isozymes and GSK-3 beta. In a cell-based functional assay, 8f and 8i effectively blocked IL-8 release induced by PKC-beta II (IC50 = 20-25 nM). In cardiovascular safety assessment, representative lead compounds bound to the hERG channel with high affinity, potently inhibited ion current in a patch-clamp experiment, and caused a dose-dependent increase of QT(c) in guinea pigs.