[4-(3-aminomethylphenyl)piperidin-1-yl]-[5-(2-fluorophenylethynyl)furan-2-yl]-methanone trifluoroacetate | 725228-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [4-(3-aminomethylphenyl)piperidin-1-yl]-[5-(2-fluorophenylethynyl)furan-2-yl]-methanone trifluoroacetate
• 英文别名: [4-(3-Aminomethylphenyl)-piperidin-1-yl]-[5-(2-fluorophenylethynyl)-furan-2-yl]-methanone trifluoroacetate；[4-[3-(aminomethyl)phenyl]piperidin-1-yl]-[5-[2-(2-fluorophenyl)ethynyl]furan-2-yl]methanone;2,2,2-trifluoroacetic acid
• CAS: 725228-46-6
• 化学式: C₂HF₃O₂*C₂₅H₂₃FN₂O₂
• 分子量: 516.492
• InChiKey: ZRCQCBZVDATCLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  96.8
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-[3-(tert-butoxycarbonylaminomethyl)phenyl]-1-[5-(2-fluorophenylethynyl)-2-furanoyl]piperidine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 [4-(3-aminomethylphenyl)piperidin-1-yl]-[5-(2-fluorophenylethynyl)furan-2-yl]-methanone trifluoroacetate
  参考文献：
  名称：

  [EN] [4-(3-AMINOMETHYLPHENYL) PIPERIDIN-1-YL]- [5-(2-FLUOROPHENYLETHYNYL)FURAN-2-YL]-METHANONE AS AN INHIBITOR OF MAST CELL TRYPTASE
  [FR] [4-(3-AMINOMETHYLPHENYL)PIPERIDIN-1-YL]-[5-(2-FLUOROPHENYLETHYNYL)FURAN-2-YL]-METHANONE EN TANT QU'INHIBITEUR DE LA TRYPTASE MASTOCYTAIRE

  摘要：

  本发明涉及到式(I)的化合物：(I)或者该化合物的前药、药学上可接受的盐或溶剂；一种包含式(I)化合物的药物组合物，以及药学上有效量的该化合物和药学上可接受的载体；将式(I)化合物用作色氨酸蛋白酶抑制剂的用途，包括将该化合物引入含有色氨酸蛋白酶的组合物中。

  公开号：

  WO2004060884A1

文献信息

• 4-(3-aminomethylphenyl)piperidin-1-yl]-[5-(2-fluorophenylethynyl)furan-2-yl]-methanone as an inhibitor of mast cell tryptase
  申请人：AVENTIS PHARMACEUTICALS INC.

  公开号：US20040192734A1

  公开（公告）日：2004-09-30

  The present invention extends to the compound of formula (I): 1 or a prodrug, pharmaceutically acceptable salt, or solvate of said compound; to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I), and a pharmaceutically acceptable carrier; the use of a compound of formula (I) as an inhibitor of tryptase comprising introducing the compound into a composition comprising tryptase.

  本发明涉及公式（I）的化合物：1或其前药、药学上可接受的盐或溶剂，以及包含公式（I）化合物的药物组合物，其中该组合物含有药学有效量的公式（I）化合物和药学上可接受的载体；本发明还涉及将公式（I）化合物引入含有tryptase的组合物中作为tryptase抑制剂的用途。
• Structure-based library design and the discovery of a potent and selective mast cell β-tryptase inhibitor as an oral therapeutic agent
  作者：Guyan Liang、Suzanne Aldous、Gregory Merriman、Julian Levell、James Pribish、Jennifer Cairns、Xin Chen、Sebastien Maignan、Magali Mathieu、Joseph Tsay、Keith Sides、Sam Rebello、Brian Whitely、Isabelle Morize、Henry W. Pauls

  DOI：10.1016/j.bmcl.2011.11.119

  日期：2012.1

  A solid phase combinatorial library was designed based on X-ray structures and in-silico models to explore an inducible S4+ pocket, which is formed by a simple side-chain rotation of Tyr95. This inducible S4+ pocket is unique to β-tryptase and does not exist for other trypsin-like serine proteases of interest. Therefore, inhibitors utilizing this pocket have inherent advantages for being selective against other proteases in the same family. A member of this library was found to be a potent and selective β-tryptase inhibitor with a suitable pharmacokinetic profile for further clinical evaluation.