2-(三甲基甲硅烷基)乙基4-(((三氟甲基)磺酰)氧基)-5,6-二氢吡啶-1(2H)-羧酸叔丁酯 | 375854-77-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 中文名称: 2-(三甲基甲硅烷基)乙基4-(((三氟甲基)磺酰)氧基)-5,6-二氢吡啶-1(2H)-羧酸叔丁酯
• 英文名称: 2-(trimethylsilyl)ethyl 1,2,3,6-tetrahydro-4-trifluoromethylsulfonyloxy-pyridine-1-carboxylate
• 英文别名: 4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid 2-trimethyl-silanyl-ethyl ester；2-(Trimethylsilyl)ethyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate；2-trimethylsilylethyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 375854-77-6
• 化学式: C₁₂H₂₀F₃NO₅SSi
• 分子量: 375.441
• InChiKey: UOCDXNSBOHQLFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.92
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-(三甲基甲硅烷基)乙基4-(((三氟甲基)磺酰)氧基)-5,6-二氢吡啶-1(2H)-羧酸叔丁酯 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 盐酸 、 四丁基氟化铵 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 20.0~50.0 ℃ 、344.75 kPa 条件下， 反应 5.5h， 生成 3-(哌啶-4-基)苄基氨基甲酸叔丁酯
  参考文献：
  名称：

  [EN] [4[4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(1H-PYRROLO-PYRIDIN-YL)-METHANONES AND SYNTHESIS THEREOF
  [FR] [4[4-(5-AMINOMÉTHYL-2-FLUORO-PHÉNYL)-PIPÉRIDIN-1-YL]-(1H-PYRROLO-PYRIDIN-YL)-MÉTHANONES ET LEUR SYNTHÈSE

  摘要：

  本发明涉及用于治疗和改善炎症性疾病的化合物和组合物。特别是，本发明涉及具有胰蛋白酶抑制活性的化合物及其中间体，包括这些化合物的药物组合物，以及治疗可通过施用胰蛋白酶抑制剂来改善的状况、疾病或失调的方法，例如但不限于哮喘和其他炎症性疾病，包括年龄相关的黄斑变性。

  公开号：

  WO2011078984A1
• 作为产物：
  描述：

  对硝基苯基三甲基硅乙基碳酸酯 在 4-二甲氨基吡啶 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.0h， 生成 2-(三甲基甲硅烷基)乙基4-(((三氟甲基)磺酰)氧基)-5,6-二氢吡啶-1(2H)-羧酸叔丁酯
  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。
• [EN] [4[4-(5-AMINOMETHYL-2-FLUORO-PHENYL)-PIPERIDIN-1-YL]-(1H-PYRROLO-PYRIDIN-YL)-METHANONES AND SYNTHESIS THEREOF<br/>[FR] [4[4-(5-AMINOMÉTHYL-2-FLUORO-PHÉNYL)-PIPÉRIDIN-1-YL]-(1H-PYRROLO-PYRIDIN-YL)-MÉTHANONES ET LEUR SYNTHÈSE
  申请人：SANOFI SA

  公开号：WO2011078984A1

  公开（公告）日：2011-06-30

  The present invention relates herein to compounds and compositions for the treatment and amelioration of inflammatory disease. Specifically the present invention relates to compounds that having a tryptase inhibition activity and the intermediates thereof, pharmaceutical compositions comprising such compounds, and a method of treating subjects suffering from a condition disease or disorder that can be ameliorated by the administration of an inhibitor of tryptase including but not limited to for example asthma and other inflammatory diseases including age-related macular degeneration.

  本发明涉及用于治疗和改善炎症性疾病的化合物和组合物。特别是，本发明涉及具有胰蛋白酶抑制活性的化合物及其中间体，包括这些化合物的药物组合物，以及治疗可通过施用胰蛋白酶抑制剂来改善的状况、疾病或失调的方法，例如但不限于哮喘和其他炎症性疾病，包括年龄相关的黄斑变性。
• 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.
• [EN] INDOLYL-PIPERIDINYL BENZYLAMINES AS BETA-TRYPTASE INHIBITORS<br/>[FR] INDOLYL-PIPÉRIDINYL BENZYLAMINES INHIBITRICES DE LA BÊTA-TRYPTASE
  申请人：SANOFI SA

  公开号：WO2011079102A1

  公开（公告）日：2011-06-30

  The present invention discloses and claims a series of substituted indolyl-piperidinyl benzylamines of formula (I), wherein R1, R2 and R3 are as described herein. More specifically, the compounds of this invention are inhibitors of β-tryptase and are, therefore, useful as pharmaceutical agents. Additionally, this invention also discloses methods of preparation of substituted indolyl-piperidinyl benzylamines. In one of the embodiments, there is provided the compounds of formula (I) wherein R3 is (II).

  本发明公开并要求一系列取代的吲哚基-哌啶基苄胺化合物，其公式为（I），其中R1、R2和R3如本文所述。更具体地说，本发明的化合物是β-tryptase的抑制剂，因此可用作药物制剂。此外，本发明还公开了取代的吲哚基-哌啶基苄胺的制备方法。在其中一个实施例中，提供了公式（I）的化合物，其中R3是（II）。