5-(N-苄基-N-甲基氨基羰基)-3-(3-甲基苄基)-6-羟基-1H-吲唑 | 1001191-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(N-苄基-N-甲基氨基羰基)-3-(3-甲基苄基)-6-羟基-1H-吲唑
• 英文名称: 5-(N-benzyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole
• 英文别名: N-benzyl-6-hydroxy-N-methyl-3-[(3-methylphenyl)methyl]-1H-indazole-5-carboxamide
• CAS: 1001191-80-5
• 化学式: C₂₄H₂₃N₃O₂
• 分子量: 385.466
• InChiKey: JTCGRDMMRLTULM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  69.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴-6-甲氧基-3-(3-甲基苄基)-1H-吲唑 在 氯化亚砜 、 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 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 20.0~100.0 ℃ 、400.01 kPa 条件下， 反应 2.0h， 生成 5-(N-苄基-N-甲基氨基羰基)-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

文献信息

• INDAZOLE DERIVATIVES FOR THE TREATMENT OF HSP90-INDUCED DISEASES
  申请人：Buchstaller Hans Peter

  公开号：US20090197882A1

  公开（公告）日：2009-08-06

  Novel indazole derivatives of the formula (I), in which R 1 -R 3 have the meanings indicated in Claim ( 1 ), are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.

  式（I）中的新型吲唑衍生物，其中R1-R3具有权利要求书（1）中指示的含义，是HSP90抑制剂，可用于制备用于治疗HSP90起作用的疾病的药物。
• INDAZOLDERIVATE ZUR BEHANDLUNG VON HSP90-INDUZIERTEN KRANKHEITEN
  申请人：Merck Patent GmbH

  公开号：EP2035391B1

  公开（公告）日：2011-11-23
• US8722903B2
  申请人：——

  公开号：US8722903B2

  公开（公告）日：2014-05-13
• Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule inhibitors of Hsp90
  作者：Hans-Peter Buchstaller、Hans-Michael Eggenweiler、Christian Sirrenberg、Ulrich Grädler、Djordje Musil、Edmund Hoppe、Astrid Zimmermann、Harry Schwartz、Joachim März、Jörg Bomke、Ansgar Wegener、Michael Wolf

  DOI：10.1016/j.bmcl.2012.04.121

  日期：2012.7

  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.