N-{3-[8-(4-bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide | 1314641-69-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: N-{3-[8-(4-bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide
• 英文别名: N-{3-[8-(4-Bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-aza bicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide；N-[[3-[8-(4-bromo-3-methyl-5-propoxythiophene-2-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl]-4-fluorophenyl]methyl]-2,2,2-trifluoroacetamide
• CAS: 1314641-69-4
• 化学式: C₂₅H₂₇BrF₄N₂O₃S
• 分子量: 591.465
• InChiKey: FGFNOPQAYAHJDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  86.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-{3-[8-(4-bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide 在 potassium carbonate 、 盐酸 作用下， 以 甲醇 、 水 、 乙醚 为溶剂， 生成 [3-(5-aminomethyl-2-fluoro-phenyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-(4-bromo-3-methyl-5-propoxy-thiophen-2-yl)-methanone hydrochloride
  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
• 作为产物：
  描述：

  N-叔丁氧羰基-去甲托品酮 在 盐酸 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 六甲基二锡 、 双(三甲基硅烷基)氨基钾 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， -78.0~110.0 ℃ 、413.7 kPa 条件下， 反应 27.17h， 生成 N-{3-[8-(4-bromo-3-methyl-5-propoxy-thiophene-2-carbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-fluoro-benzyl}-2,2,2-trifluoro-acetamide
  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.