3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-oxoethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid | 950700-51-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-oxoethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid
• 英文别名: 3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-[2-(4-fluorophenyl)-2-oxoethoxy]indol-2-yl]-2,2-dimethylpropanoic acid
• CAS: 950700-51-3
• 化学式: C₃₂H₃₃ClFNO₄S
• 分子量: 582.136
• InChiKey: MQYFYSIYLNGLBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  93.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-oxoethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid 在 sodium tetrahydroborate 作用下， 生成 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-hydroxyethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid
  参考文献：
  名称：

  5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)—A potent FLAP inhibitor

  摘要：

  A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.131
• 作为产物：
  描述：

  ethyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-oxoethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(2-(4-fluorophenyl)-2-oxoethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid
  参考文献：
  名称：

  5-Lipoxygenase-activating protein inhibitors. Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid (AM679)—A potent FLAP inhibitor

  摘要：

  A series of potent 5-lipoxygenase-activating protein (FLAP) inhibitors are herein described. SAR studies focused on the discovery of novel alicyclic moieties appended to an indole core to optimize potency, physical properties and off-target activities. Subsequent SAR on the N-benzyl substituent of the indole led to the discovery of compound 39 (AM679) which showed potent inhibition of leukotrienes in human blood and in a rodent bronchoalvelolar lavage (BAL) challenge model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.131

文献信息

• 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Hutchinson Howard John

  公开号：US20070219206A1

  公开（公告）日：2007-09-20

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本文描述了一些化合物和含有这些化合物的制药组合物，这些化合物可以调节5-脂氧合酶激活蛋白（FLAP）的活性。本文还描述了使用这种FLAP调节剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他依赖于白三烯或介导白三烯的疾病或病症。
• 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors
  申请人：Hutchinson John Howard

  公开号：US20110034514A1

  公开（公告）日：2011-02-10

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本文描述了含有这些化合物的药物组合物，这些化合物可以调节5-脂氧合酶激活蛋白（FLAP）的活性。本文还描述了使用这些FLAP调节剂的方法，单独或与其他化合物组合，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的疾病或病症。
• US7834037B2
  申请人：——

  公开号：US7834037B2

  公开（公告）日：2010-11-16
• [EN] 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEINE D'ACTIVATION DE LA 5-LIPOXYGENASE (FLAP)
  申请人：AMIRA PHARMACEUTICALS INC

  公开号：WO2007056228A2

  公开（公告）日：2007-05-18

  [EN] Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.
  [FR] L'invention concerne des composés et des compositions pharmaceutiques contenant de tels composés, qui permettent de moduler l'activité de la protéine d'activation de la 5-lipoxygénase (FLAP). Cette invention a aussi pour objet des méthodes d'utilisation de modulateurs de cette protéine d'activation de la 5-lipoxygénase (FLAP), seuls et en combinaison avec d'autres composés, dans le traitement de troubles ou de maladies respiratoires, cardio-vasculaires et dépendants de la leukotriène ou médiés par la leukotriène.
• [EN] 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS<br/>[FR] INHIBITEURS DE PROTÉINE FLAP (5-LIPOXYGENASE-ACTIVATING PROTEIN)
  申请人：AMIRA PHARMACEUTICALS INC

  公开号：WO2008137609A1

  公开（公告）日：2008-11-13

  [EN] Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.
  [FR] La présente invention concerne des composés et des compositions pharmaceutiques contenant de telles compositions, qui modulent l'activité de la protéine FLAP (5-Lipoxygenase-Activating Protein = protéine activant la 5-lipoxygénase). L'invention concerne également des procédés pour l'utilisation de tels modulateurs de la FLAP, seuls ou en association avec d'autres composés, pour le traitement d'états ou d'affections respiratoires, cardiovasculaires, ou autrement dépendants des leukotriènes ou découlant d'une médiation par les leukotriènes.