Methyl 1-(2-methoxyethyl)-3-(trifluoroacetyl)-1h-indole-4-carboxylate | 1256919-21-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Methyl 1-(2-methoxyethyl)-3-(trifluoroacetyl)-1h-indole-4-carboxylate
• 英文别名: methyl 1-(2-methoxyethyl)-3-(2,2,2-trifluoroacetyl)indole-4-carboxylate
• CAS: 1256919-21-7
• 化学式: C₁₅H₁₄F₃NO₄
• 分子量: 329.276
• InChiKey: HHDCYNOQEHXRGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methyl 1-(2-methoxyethyl)-3-(trifluoroacetyl)-1h-indole-4-carboxylate 在 甲醇 、 sodium hydroxide 作用下， 反应 2.0h， 以91%的产率得到1-(2-methoxy-ethyl)-3-(2,2,2-trifluoro-ethanoyl)-1H-indole-4-carboxylic acid
  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：

  Methyl 1-(2-methoxyethyl)indole-4-carboxylate 、 三氟乙酸酐 以 N,N-二甲基甲酰胺 为溶剂， 以55%的产率得到Methyl 1-(2-methoxyethyl)-3-(trifluoroacetyl)-1h-indole-4-carboxylate
  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

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.