3-{2-fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester | 1314641-63-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-{2-fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester
• 英文别名: 3-{2-Fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester；tert-butyl 3-[2-fluoro-5-[[(2,2,2-trifluoroacetyl)amino]methyl]phenyl]-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate
• CAS: 1314641-63-8
• 化学式: C₂₁H₂₄F₄N₂O₃
• 分子量: 428.427
• InChiKey: USXIQNPPXDFEPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-{2-fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester 在 钯 二氯甲烷 、 magnesium sulfate 作用下， 以 甲醇 为溶剂， 反应 9.0h， 以to yield 4.45 g (90%) of the product as a white foam的产率得到3-{2-fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  TROPINONE BENZYLAMINES AS BETA-TRYPTASE INHIBITORS

  摘要：

  本发明披露并声明了一系列公式（I）的取代的托品酮苄胺化合物：这些化合物是β-色氨酸酶的抑制剂，因此可用作药物。此外，本发明还披露了取代的托品酮苄胺的制备方法。

  公开号：

  US20120238600A1
• 作为产物：
  描述：

  3-溴-4-氟苯甲胺 盐酸盐 在 四(三苯基膦)钯 、 六甲基二锡 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 8.23h， 生成 3-{2-fluoro-5-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  A β-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity

  摘要：

  Tropanylamide was investigated as a possible scaffold for beta-tryptase inhibitors with a basic benzylamine P1 group and a substituted thiophene P4 group. Comparing to piperidinylamide, the tropanylamide scaffold is much more rigid, which presents less opportunity for the inhibitor to bind with off-target proteins, such as cytochrome P450, SSAO, and hERG potassium channel. The proposed binding mode was further confirmed by an in-house X-ray structure through co-crystallization. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.127

文献信息

• [EN] TROPINONE BENZYLAMINES AS BETA-TRYPTASE INHIBITORS<br/>[FR] BENZYLAMINES DE TROPINONE UTILISÉS COMME INHIBITEURS DE LA BÊTA-TRYPTASE
  申请人：SANOFI SA

  公开号：WO2011087652A1

  公开（公告）日：2011-07-21

  The present invention discloses and claims a series of substituted tropinone benzylamines of formula (I). 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 tropinone benzylamines.

  本发明公开并要求一系列取代托品酮苄胺的公式（I）化合物。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托品酮苄胺的制备方法。
• TROPINONE BENZYLAMINES AS BETA-TRYPTASE INHIBITORS
  申请人：CHOI-SLEDESKI Yong Mi

  公开号：US20120238600A1

  公开（公告）日：2012-09-20

  The present invention discloses and claims a series of substituted tropinone benzylamines of formula (I): 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 tropinone benzylamines.

  本发明披露并声明了一系列公式（I）的取代的托品酮苄胺化合物：这些化合物是β-色氨酸酶的抑制剂，因此可用作药物。此外，本发明还披露了取代的托品酮苄胺的制备方法。
• A β-tryptase inhibitor with a tropanylamide scaffold to improve in vitro stability and to lower hERG channel binding affinity
  作者：Guyan Liang、Yong Mi Choi-Sledeski、Patrick Shum、Xin Chen、Gregory B. Poli、Vasant Kumar、Anne Minnich、Qingping Wang、Joseph Tsay、Keith Sides、Jiesheng Kang、Ying Zhang

  DOI：10.1016/j.bmcl.2011.12.127

  日期：2012.2

  Tropanylamide was investigated as a possible scaffold for beta-tryptase inhibitors with a basic benzylamine P1 group and a substituted thiophene P4 group. Comparing to piperidinylamide, the tropanylamide scaffold is much more rigid, which presents less opportunity for the inhibitor to bind with off-target proteins, such as cytochrome P450, SSAO, and hERG potassium channel. The proposed binding mode was further confirmed by an in-house X-ray structure through co-crystallization. (C) 2011 Elsevier Ltd. All rights reserved.