3-(methylthio)-1-phenyl-1H-indazol-6-amine | 1254069-38-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(methylthio)-1-phenyl-1H-indazol-6-amine
• 英文别名: 3-Methylsulfanyl-1-phenyl-1H-indazol-6-ylamine；3-methylsulfanyl-1-phenylindazol-6-amine
• CAS: 1254069-38-9
• 化学式: C₁₄H₁₃N₃S
• 分子量: 255.343
• InChiKey: NOHZWALYMOSRQE-UHFFFAOYSA-N

物化性质

• 沸点：
  402.0±27.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(methylthio)-1-phenyl-1H-indazol-6-amine 在 盐酸 、 水 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 生成 N-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)pyrrolidine-3-carboxamide
  参考文献：
  名称：

  Optimization of a pyrazole hit from FBDD into a novel series of indazoles as ketohexokinase inhibitors

  摘要：

  A series of indazoles have been discovered as KHK inhibitors from a pyrazole hit identified through fragment-based drug discovery (FBDD). The optimization process guided by both X-ray crystallography and solution activity resulted in lead-like compounds with good pharmaceutical properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.067
• 作为产物：
  描述：

  2-氨基-4-硝基苯甲酸 在 palladium on activated charcoal 盐酸 、 tetraphosphorus decasulfide 、 氢气 、 caesium carbonate 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙酸乙酯 、 乙腈 、 xylene 为溶剂， 反应 6.22h， 生成 3-(methylthio)-1-phenyl-1H-indazol-6-amine
  参考文献：
  名称：

  INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS

  摘要：

  本发明涉及替代吲唑化合物，这些化合物的药物组合物以及它们的使用方法。本发明的化合物是酮己糖激酶（KHK）抑制剂，可用于治疗或改善由KHK介导的代谢紊乱和/或疾病，如肥胖、Ⅱ型糖尿病和X型代谢综合征。

  公开号：

  US20110263559A1

文献信息

• Indazole compounds useful as ketohexokinase inhibitors
  申请人：Zhang Xuqing

  公开号：US08822447B2

  公开（公告）日：2014-09-02

  The present invention is directed to substituted indazole compounds of formula (I) pharmaceutical compositions of these compounds and methods of use thereof. The compounds of the present invention are ketohexokinase (KHK) inhibitors, useful for treating or ameliorating a KHK mediated metabolic disorders and/or diseases such as obesity, Type II diabetes mellitus and Metabolic Syndrome X.

  本发明涉及公式（I）的取代吲唑化合物，这些化合物的药物组合物以及使用它们的方法。本发明的化合物是酮基己糖激酶（KHK）抑制剂，可用于治疗或改善KHK介导的代谢紊乱和/或疾病，如肥胖症，2型糖尿病和代谢综合征X。
• Electron Density Guided Fragment-Based Lead Discovery of Ketohexokinase Inhibitors
  作者：Alan C. Gibbs、Marta C. Abad、Xuqing Zhang、Brett A. Tounge、Francis A. Lewandowski、Geoffrey T. Struble、Weimei Sun、Zhihua Sui、Lawrence C. Kuo

  DOI：10.1021/jm100677s

  日期：2010.11.25

  A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments to leadlike compounds. Applying electron density of fragments within the protein binding site as defined by X-ray crystallography, one can generate target specific leads without the use of affinity data. Our approach contrasts with most fragment-based drug design methodology where solution activity is a main design guide. Herein we describe the discovery of submicromolar ketohexokinase inhibitors with promising druglike properties.
• US8822447B2
  申请人：——

  公开号：US8822447B2

  公开（公告）日：2014-09-02
• US9771375B2
  申请人：——

  公开号：US9771375B2

  公开（公告）日：2017-09-26
• [EN] INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS<br/>[FR] INDAZOLES EN TANT QU'INHIBITEURS DE CÉTOHEXOKINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2011133750A1

  公开（公告）日：2011-10-27

  The present invention is directed to substituted indazole compounds, pharmaceutical compositions of these compounds and methods of use thereof. The compounds of the present invention are ketohexokinase (KHK) inhibitors, useful for treating or ameliorating a KHK mediated metabolic disorders and / or diseases such as obesity, Type II diabetes mellitus and Metabolic Syndrome X.