2-{9-[(Z,E)-hydroxyimino]-9H-fluoren-4-yl}-1H-imidazo[4,5-c]pyridine | 915139-07-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 2-{9-[(Z,E)-hydroxyimino]-9H-fluoren-4-yl}-1H-imidazo[4,5-c]pyridine
• 英文别名: (NE)-N-[4-(3H-imidazo[4,5-c]pyridin-2-yl)fluoren-9-ylidene]hydroxylamine
• CAS: 915139-07-0
• 化学式: C₁₉H₁₂N₄O
• 分子量: 312.33
• InChiKey: NSTCRELNQHRYCQ-PTGBLXJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-(3H-imidazo[4,5-c]pyridin-2-yl)-fluoren-9-one 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 生成 (NZ)-N-[4-(3H-imidazo[4,5-c]pyridin-2-yl)fluoren-9-ylidene]hydroxylamine 、 2-{9-[(Z,E)-hydroxyimino]-9H-fluoren-4-yl}-1H-imidazo[4,5-c]pyridine
  参考文献：
  名称：

  Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof

  摘要：

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。

  公开号：

  US20080153837A1

文献信息

• Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof
  申请人：MAILLIET Patrick

  公开号：US20080153837A1

  公开（公告）日：2008-06-26

  This invention relates to derivatives of 4-(benzimidazol-2-yl)fluorene and 4-(azabenzimidazol-2-yl)fluorene, to pharmaceutical compositions comprising such derivatives, and to methods of treatment of disorders related to Hsp90 protein activity, comprising administering such derivatives.

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。
• NOUVEAUX DERIVES DU FLUORENE, COMPOSITIONS LES CONTENANT ET UTILISATION
  申请人：Aventis Pharma S.A.

  公开号：EP1888579B1

  公开（公告）日：2011-08-03
• US7674795B2
  申请人：——

  公开号：US7674795B2

  公开（公告）日：2010-03-09
• Tricyclic Series of Heat Shock Protein 90 (Hsp90) Inhibitors Part I: Discovery of Tricyclic Imidazo[4,5-<i>c</i>]pyridines as Potent Inhibitors of the Hsp90 Molecular Chaperone
  作者：François Vallée、Chantal Carrez、Fabienne Pilorge、Alain Dupuy、Annick Parent、Luc Bertin、Fabienne Thompson、Paul Ferrari、Florence Fassy、Annabelle Lamberton、Anne Thomas、Rosalia Arrebola、Stéphane Guerif、Alexandre Rohaut、Victor Certal、Jean-Marie Ruxer、Cécile Delorme、Alain Jouanen、Jacques Dumas、Claudine Grépin、Cécile Combeau、Hélène Goulaouic、Norbert Dereu、Vincent Mikol、Patrick Mailliet、Hervé Minoux

  DOI：10.1021/jm200784m

  日期：2011.10.27

  A novel class of heat shock protein 90 (Hsp90) inhibitors was developed after a low throughput screen (LTS) of a focused library containing approximately 21K compounds selected by virtual screening. The initial [1-3-H-imidazo[4,5-c]pyridin-2-yl}-3,4- dihydro-2H-pyrido[2,1-a]isoindole-6-one] (1) compound showed moderate activity (IC50 = 7.6 mu M on Hsp82, the yeast homologue of Hsp90). A high-resolution X-ray structure shows that compound 1 binds into an "induced" hydrophobic pocket, 10-15 angstrom away from the ATP/resorcinol binding site. Iterative cycles of structure-based drug design (SBDD) and chemical synthesis led to the design and preparation of analogues with improved affinity. These optimized molecules make productive interactions within the ATP binding site as reported by other Hsp90 inhibitors. This resulted in compound 8, which is a highly potent inhibitor in biochemical and cellular assays (K-d = 0.35 nM on Hsp90; IC50 = 30 nM on SKBr3 mammary carcinoma cells) and in an in vivo leukemia model.