3-(4-{2-Fluoro-5[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-piperidine-1-carbonyl)-1-(2-methoxy-ethyl)-1H-indole-4-carboxylic acid dimethylamide | 1256919-24-0

• 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: 3-(4-{2-Fluoro-5[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-piperidine-1-carbonyl)-1-(2-methoxy-ethyl)-1H-indole-4-carboxylic acid dimethylamide
• 英文别名: 3-[4-[2-fluoro-5-[[(2,2,2-trifluoroacetyl)amino]methyl]phenyl]piperidine-1-carbonyl]-1-(2-methoxyethyl)-N,N-dimethylindole-4-carboxamide
• CAS: 1256919-24-0
• 化学式: C₂₉H₃₂F₄N₄O₄
• 分子量: 576.591
• InChiKey: SMYUXFMQLQLJHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-(4-{2-Fluoro-5[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-piperidine-1-carbonyl)-1-(2-methoxy-ethyl)-1H-indole-4-carboxylic acid dimethylamide 在 甲醇 、 水 、 potassium carbonate 作用下， 以50%的产率得到3-((4-[5-(aminomethyl)-2-fluorophenyl]piperidin-1-yl)carbonyl)-1-(2-methoxyethyl)-N,N-dimethyl-1h-indole-4-carboxamide
  参考文献：
  名称：

  A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO)

  摘要：

  Anovel beta-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so that entropic penaltywas decreased. More importantly, this constrained conformation limited the accessibility of this molecule to anti-targets, especially SSAO, so that an enhanced metabolic profile was achieved. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.141
• 作为产物：
  描述：

  4-dimethylcarbamoyl-1-(2-methoxy-ethyl)-1H-indole-3-carboxylic acid 、 2,2,2-trifluoro-N-(4-fluoro-3-piperidin-4-yl-benzyl)acetamide hydrochloride 生成 3-(4-{2-Fluoro-5[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-piperidine-1-carbonyl)-1-(2-methoxy-ethyl)-1H-indole-4-carboxylic acid dimethylamide
  参考文献：
  名称：

  INDOLYL-PIPERIDINYL BENZYLAMINES AS BETA-TRYPTASE INHIBITORS

  摘要：

  本发明披露和声称一系列被取代的indolyl-piperidinyl benzylamines，其化学式为其中R1、R2、R4和R5如本文所述。更具体地说，本发明的化合物是β-tryptase的抑制剂，因此可用作制药剂。此外，本发明还披露了取代的indolyl-piperidinyl benzylamines的制备方法。

  公开号：

  US20120245161A1

文献信息

• [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）。
• INDOLYL-PIPERIDINYL BENZYLAMINES AS BETA-TRYPTASE INHIBITORS
  申请人：CHOI-SLEDESKI Yong Mi

  公开号：US20120245161A1

  公开（公告）日：2012-09-27

  The present invention discloses and claims a series of substituted indolyl-piperidinyl benzylamines of the formula wherein R1, R2, R4 and R5 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.

  本发明披露和声称一系列被取代的indolyl-piperidinyl benzylamines，其化学式为其中R1、R2、R4和R5如本文所述。更具体地说，本发明的化合物是β-tryptase的抑制剂，因此可用作制药剂。此外，本发明还披露了取代的indolyl-piperidinyl benzylamines的制备方法。
• A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO)
  作者：Guyan Liang、Yong Mi Choi-Sledeski、Gregory Poli、Xin Chen、Patrick Shum、Anne Minnich、Qingping Wang、Joseph Tsay、Keith Sides、Jennifer Cairns、Gregory Stoklosa、Thaddeus Nieduzak、Zhicheng Zhao、Jie Wang、Roy J. Vaz

  DOI：10.1016/j.bmcl.2010.08.141

  日期：2010.11

  Anovel beta-tryptase inhibitor with a basic benzylamine P1 group, a piperidine-amide linker, and a substituted indole P4 group was discovered. A substitution at 4-indole position was introduced to constrain the conformational flexibility of the inhibitor to the bioactive conformation exhibited by X-ray structures so that entropic penaltywas decreased. More importantly, this constrained conformation limited the accessibility of this molecule to anti-targets, especially SSAO, so that an enhanced metabolic profile was achieved. (C) 2010 Elsevier Ltd. All rights reserved.