methyl 6-methoxy-3-(3-methylbenzyl)-1H-indazole-5-carboxylate | 1384440-42-9

• 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: methyl 6-methoxy-3-(3-methylbenzyl)-1H-indazole-5-carboxylate
• CAS: 1384440-42-9
• 化学式: C₁₈H₁₈N₂O₃
• 分子量: 310.353
• InChiKey: KNFMGMPKWJDNNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.26
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  64.21
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 6-methoxy-3-(3-methylbenzyl)-1H-indazole-5-carboxylate 在 氯化亚砜 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 5-(N-苄基-N-乙基氨基羰基)-3-(3-甲基苄基)-6-羟基-1H-吲唑
  参考文献：
  名称：

  Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule inhibitors of Hsp90

  摘要：

  Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe the identification of novel small molecular weight inhibitors of Hsp90 using a fragment based approach. Fragments were selected by docking, tested in a biochemical assay and the confirmed hits were crystallized. Information gained from X-ray structures of these fragments and other chemotypes was used to drive the fragment evolution process. Optimization of these high mu M binders resulted in 3-benzylindazole derivatives with significantly improved affinity and anti-proliferative effects in different human cancer cell lines. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.121
• 作为产物：
  描述：

  1-(5-Bromo-2-fluoro-4-methoxyphenyl)-2-(3-methylphenyl)ethanone 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三乙胺 、 肼 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 100.0 ℃ 、400.01 kPa 条件下， 生成 methyl 6-methoxy-3-(3-methylbenzyl)-1H-indazole-5-carboxylate
  参考文献：
  名称：

  Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule inhibitors of Hsp90

  摘要：

  Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe the identification of novel small molecular weight inhibitors of Hsp90 using a fragment based approach. Fragments were selected by docking, tested in a biochemical assay and the confirmed hits were crystallized. Information gained from X-ray structures of these fragments and other chemotypes was used to drive the fragment evolution process. Optimization of these high mu M binders resulted in 3-benzylindazole derivatives with significantly improved affinity and anti-proliferative effects in different human cancer cell lines. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.121