N-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)piperidine-4-carboxamide hydrochloride | 1254069-36-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)piperidine-4-carboxamide hydrochloride
• 英文别名: N-(3-methylsulfanyl-1-phenylindazol-6-yl)piperidine-4-carboxamide;hydrochloride
• CAS: 1254069-36-7
• 化学式: C₂₀H₂₂N₄OS*ClH
• 分子量: 402.948
• InChiKey: CGRARMVNWQVWKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-硝基苯甲酸 在 盐酸 、 tetraphosphorus decasulfide 、 5% Pd(II)/C(eggshell) 、 氢气 、 caesium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium nitrite 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.05h， 生成 N-(3-(methylthio)-1-phenyl-1H-indazol-6-yl)piperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Electron Density Guided Fragment-Based Lead Discovery of Ketohexokinase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm100677s

文献信息

• INDAZOLE COMPOUNDS USEFUL AS KETOHEXOKINASE INHIBITORS
  申请人：ZHANG Xuqing

  公开号：US20110263559A1

  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.

  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。
• 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.
• 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.