3-{3-tert-butylsulfanyl-5-hydroxy-1-[4-(6-methoxy-pyridazin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester | 1031435-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-{3-tert-butylsulfanyl-5-hydroxy-1-[4-(6-methoxy-pyridazin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester
• 英文别名: ethyl 3-[3-tert-butylsulfanyl-5-hydroxy-1-[[4-(6-methoxypyridazin-3-yl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoate
• CAS: 1031435-34-3
• 化学式: C₃₁H₃₇N₃O₄S
• 分子量: 547.718
• InChiKey: CZUJRWQTGGIOOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-{3-tert-butylsulfanyl-5-hydroxy-1-[4-(6-methoxy-pyridazin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester 、 (S)-2-((甲苯磺酰氧基)甲基)二氢吲哚-1-羧酸叔丁酯 在 caesium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-{3-tert-butylsulfanyl-2-(2-carboxy-2-methyl-propyl)-1-(4-(6-methoxy-pyridazin-3-yl)-benzyl)-1H-indol-5-yloxymethyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  WO2008/67566

  摘要：

  公开号：
• 作为产物：
  描述：

  3-{3-tert-butylsulfanyl-5-hydroxy-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester 、 3-氯-6-甲氧基哒嗪 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.17h， 生成 3-{3-tert-butylsulfanyl-5-hydroxy-1-[4-(6-methoxy-pyridazin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester
  参考文献：
  名称：

  WO2008/67566

  摘要：

  公开号：

文献信息

• COMPOSITIONS AND TREATMENTS COMPRISING 5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS AND NITRIC OXIDE MODULATORS
  申请人：Hutchinson John H.

  公开号：US20100068301A1

  公开（公告）日：2010-03-18

  Disclosed herein are compositions and compounds that combine an inhibitor of 5 -lipoxygenase activating protein (FLAP) and a modulator of NO levels in a mammal. The NO modulator can be an agent that induces the production of NO in a mammal, or can be an agent that itself produces NO in the mammal. Further disclosed herein are strategies for synthesizing such compounds, and methods for testing whether the combination compounds and compositions provide a desired benefit. Also disclosed herein are pharmaceutical compositions and formulations that combine a FLAP inhibitor and an NO modulator. Further described herein are methods for using such compositions and compounds for the treatment of diseases, conditions, and disorders in a mammal, including a human. Such treatment methods include the separate administration of a FLAP inhibitor and a NO modulator to the mammal, and the simultaneous administration of a FLAP inhibitor and a NO modulator to the mammal.

  本文揭示了一种将5-脂氧合酶激活蛋白（FLAP）抑制剂和哺乳动物中NO水平调节剂结合的组合物和化合物。NO调节剂可以是在哺乳动物中诱导NO产生的药物，也可以是在哺乳动物中自身产生NO的药物。本文还揭示了合成这种化合物的策略，以及测试组合化合物和组合物是否提供所需益处的方法。本文还揭示了将FLAP抑制剂和NO调节剂结合的制药组合物和配方。本文还进一步描述了使用这些组合物和化合物治疗哺乳动物（包括人类）的疾病、状况和障碍的方法。这种治疗方法包括将FLAP抑制剂和NO调节剂分别给哺乳动物，以及同时给哺乳动物FLAP抑制剂和NO调节剂。
• 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
  作者：Nicholas Stock、Christopher Baccei、Gretchen Bain、Alex Broadhead、Charles Chapman、Janice Darlington、Christopher King、Catherine Lee、Yiwei Li、Daniel S. Lorrain、Pat Prodanovich、Haojing Rong、Angelina Santini、Jasmine Zunic、Jilly F. Evans、John H. Hutchinson、Peppi Prasit

  DOI：10.1016/j.bmcl.2009.10.131

  日期：2010.1

  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.
• [EN] COMPOSITIONS AND TREATMENTS COMPRISING 5-LIPOXYGENASE-ACTIVATING PROTEIN INHIBITORS AND NITRIC OXIDE MODULATORS<br/>[FR] COMPOSITIONS ET TRAITEMENTS COMPRENANT DES INHIBITEURS DE LA PROTÉINE ACTIVANT LA 5-LIPOXYGÉNASE ET DES MODULATEURS DE L'OXYDE NITRIQUE
  申请人：AMIRA PHARMACEUTICALS INC

  公开号：WO2008067566A1

  公开（公告）日：2008-06-05

  [EN] Disclosed herein are compositions and compounds that combine an inhibitor of 5-lipoxygenase activating protein (FLAP) and a modulator of NO levels in a mammal. The NO modulator can be an agent that induces the production of NO in a mammal, or can be an agent that itself produces NO in the mammal. Further disclosed herein are strategies for synthesizing such compounds, and methods for testing whether the combination compounds and compositions provide a desired benefit. Also disclosed herein are pharmaceutical compositions and formulations that combine a FLAP inhibitor and an NO modulator. Further described herein are methods for using such compositions and compounds for the treatment of diseases, conditions, and disorders in a mammal, including a human. Such treatment methods include the separate administration of a FLAP inhibitor and a NO modulator to the mammal, and the simultaneous administration of a FLAP inhibitor and a NO modulator to the mammal.
  [FR] Cette invention concerne des compositions et des composés qui associent un inhibiteur de la protéine activant la 5-lipoxygénase (FLAP) et un modulateur des taux d'oxyde nitrique (NO) chez un mammifère. Le modulateur de NO peut être un agent qui induit la production de NO chez ledit mammifère, ou il peut s'agir d'un agent qui produit lui-même du NO chez le mammifère. Par ailleurs, l'invention concerne des stratégies permettant de synthétiser ces composés, et des procédés permettant d'évaluer si l'association composés et compositions apporte le bénéfice escompté. Des compositions et des formulations pharmaceutiques, associant un inhibiteur de la protéine FLAP et un modulateur de NO, sont également décrites. L'invention décrit aussi des procédés utilisant ces compositions et ces composés pour traiter des maladies, des affections et des troubles chez un mammifère, l'homme y compris. Parmi ces procédés thérapeutiques figurent l'administration séparée d'un inhibiteur de la protéine FLAP et d'un modulateur de NO chez le mammifère, et l'administration simultanée d'un inhibiteur de la protéine FLAP et d'un modulateur de NO chez le mammifère.
• WO2008/67566
  申请人：——

  公开号：——

  公开（公告）日：——