4-(3-methylsulfanyl-1-phenyl-1H-indazol-6-ylcarbamoyl)piperidine-1-carboxylicacid tert-butyl ester | 1254069-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-methylsulfanyl-1-phenyl-1H-indazol-6-ylcarbamoyl)piperidine-1-carboxylicacid tert-butyl ester
• CAS: 1254069-41-4
• 化学式: C₂₅H₃₀N₄O₃S
• 分子量: 466.604
• InChiKey: GKROZNMBNWOPPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.33
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.46
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-(3-methylsulfanyl-1-phenyl-1H-indazol-6-ylcarbamoyl)piperidine-1-carboxylicacid tert-butyl ester 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以52%的产率得到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
• 作为产物：
  描述：

  6-nitro-1-phenyl-1,2-dihydroindazol-3-thione 在 palladium on carbon 、 氢气 、 caesium carbonate 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 生成 4-(3-methylsulfanyl-1-phenyl-1H-indazol-6-ylcarbamoyl)piperidine-1-carboxylicacid tert-butyl ester
  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