2-(trimethylsilanyl)ethyl 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylate hydrochloride

• 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: 2-(trimethylsilanyl)ethyl 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylate hydrochloride
• 英文别名: 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester hydrochloride；4-(3-aminomethyl-phenyl)-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester；2-(Trimethylsilyl)ethyl 4-(3-(aminomethyl)phenyl)-piperidine-1-carboxylate hydrochloride；2-trimethylsilylethyl 4-[3-(aminomethyl)phenyl]piperidine-1-carboxylate;hydrochloride
• 化学式: C₁₈H₃₀N₂O₂Si*ClH
• 分子量: 370.995
• InChiKey: KNFSJPOXYGHBPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  55.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(trimethylsilanyl)ethyl 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylate hydrochloride 在 2-二甲氨基吡啶 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 N-甲基乙酰胺 为溶剂， 生成 (3-piperidin-4-yl-benzyl) carbamate
  参考文献：
  名称：

  Chemical compounds

  摘要：

  本文提供了具有胰蛋白酶抑制活性的新颖和有用化合物，包括含有这些化合物的药物组合物，以及治疗患有可以通过给予胰蛋白酶抑制剂（例如哮喘和炎症性疾病等）而得到改善的疾病、疾病或紊乱的方法。

  公开号：

  US20030187020A1
• 作为产物：
  描述：

  对硝基苯基三甲基硅乙基碳酸酯 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 氢气 、 sodium carbonate 、 三乙胺 、 lithium chloride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 90.0 ℃ 、344.74 kPa 条件下， 反应 10.5h， 生成 2-(trimethylsilanyl)ethyl 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylate hydrochloride
  参考文献：
  名称：

  Structure based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase

  摘要：

  Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase beta is the most important form released during mast cell activation in allergic diseases. It is shown to have numerous pro-inflammatory cellular activities in vitro, and in animal models tryptase provokes broncho-constriction and induces a cellular inflammatory infiltrate characteristic of human asthma. Screening of in-house inhibitors of factor Xa (a closely related serine protease) identified beta-amidoester benzamidines as potent inhibitors of recombinant human betaII tryptase. X-ray structure driven template modification and exchange of the benzamidine to optimize potency and pharmacokinetic properties gave selective, potent and orally bioavailable 4-(3-aminomethyl phenyl)piperidinyl-1-amides.

  DOI：

  10.1016/j.bmc.2005.02.014

文献信息

• [EN] [4-(3-AMINOMETHYLPHENYL) PIPERIDIN-1-YL]- [5-(2-FLUOROPHENYLETHYNYL)FURAN-2-YL]-METHANONE AS AN INHIBITOR OF MAST CELL TRYPTASE<br/>[FR] [4-(3-AMINOMETHYLPHENYL)PIPERIDIN-1-YL]-[5-(2-FLUOROPHENYLETHYNYL)FURAN-2-YL]-METHANONE EN TANT QU'INHIBITEUR DE LA TRYPTASE MASTOCYTAIRE
  申请人：AVENTIS PHARMA INC

  公开号：WO2004060884A1

  公开（公告）日：2004-07-22

  The present invention extends to the compund of formula (I): (I) or a prodrug, pharmaceutically acceptable salt, or solvate of said compound; to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of forumula (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。
• 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 design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase
  作者：Julian Levell、Peter Astles、Paul Eastwood、Jennifer Cairns、Olivier Houille、Suzanne Aldous、Gregory Merriman、Brian Whiteley、James Pribish、Mark Czekaj、Guyan Liang、Sebastien Maignan、Jean-Pierre Guilloteau、Alain Dupuy、Jane Davidson、Trevor Harrison、Andrew Morley、Simon Watson、Garry Fenton、Clive McCarthy、Joseph Romano、Rose Mathew、Darren Engers、Michael Gardyan、Keith Sides、Jennifer Kwong、Joseph Tsay、Sam Rebello、Liduo Shen、Jie Wang、Yongyi Luo、Odessa Giardino、Heng-Keang Lim、Keith Smith、Henry Pauls

  DOI：10.1016/j.bmc.2005.02.014

  日期：2005.4

  Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase beta is the most important form released during mast cell activation in allergic diseases. It is shown to have numerous pro-inflammatory cellular activities in vitro, and in animal models tryptase provokes broncho-constriction and induces a cellular inflammatory infiltrate characteristic of human asthma. Screening of in-house inhibitors of factor Xa (a closely related serine protease) identified beta-amidoester benzamidines as potent inhibitors of recombinant human betaII tryptase. X-ray structure driven template modification and exchange of the benzamidine to optimize potency and pharmacokinetic properties gave selective, potent and orally bioavailable 4-(3-aminomethyl phenyl)piperidinyl-1-amides.
• Chemical compounds
  申请人：——

  公开号：US20030187020A1

  公开（公告）日：2003-10-02

  Provided herein are novel and useful compounds having a tryptase inhibition activity, pharmaceutical compositions comprising such compounds, and methods treating subjects suffering from a condition, disease, or disorder that can be ameliorated by the administration of an inhibitor of tryptase, e.g., asthma and inflammatory diseases, to name only a few.

  本文提供了具有胰蛋白酶抑制活性的新颖和有用化合物，包括含有这些化合物的药物组合物，以及治疗患有可以通过给予胰蛋白酶抑制剂（例如哮喘和炎症性疾病等）而得到改善的疾病、疾病或紊乱的方法。