2,6-dimethyl-3-thiomethyl-7-azaindole | 850785-43-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 2,6-dimethyl-3-thiomethyl-7-azaindole
• 英文别名: 2,6-dimethyl-3-(methylthio)-1H-pyrrolo[2,3-b]pyridine；2,6-dimethyl-3-methylsulfanyl-1H-pyrrolo[2,3-b]pyridine
• CAS: 850785-43-2
• 化学式: C₁₀H₁₂N₂S
• 分子量: 192.285
• InChiKey: UBQLWEAGTPZIHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  54
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-3-thiomethyl-7-azaindole 在 三乙基硅烷 、 aluminum (III) chloride 、 氢气 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 32.0h， 生成 methyl 2-(2,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-3-yl)acetate
  参考文献：
  名称：

  Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP₂ Receptor Antagonist for Treatment of Asthma

  摘要：

  Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-ypacetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.

  DOI：

  10.1021/acsmedchemlett.7b00157
• 作为产物：
  描述：

  2-氨基-6-甲基吡啶 、 1-甲基硫代-2-丙酮 在 次氯酸叔丁酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2,6-dimethyl-3-thiomethyl-7-azaindole
  参考文献：
  名称：

  [EN] ANTIDIABETIC AZAINDOLES AND DIAZAINDOLES
  [FR] AZAINDOLES ET DIAZAINDOLES ANTIDIABÉTIQUES

  摘要：

  在5-成员环上具有芳香基团的氮杂吲哚和二氮杂吲哚是PPAR受体的激动剂或部分激动剂，并可用于治疗和控制2型糖尿病及与之常相关的高血糖、血脂异常、高脂血症、高胆固醇血症、高甘油三酯血症和肥胖症状。

  公开号：

  WO2009005672A1

文献信息

• [EN] ANTIDIABETIC AZAINDOLES AND DIAZAINDOLES<br/>[FR] AZAINDOLES ET DIAZAINDOLES ANTIDIABÉTIQUES
  申请人：MERCK & CO INC

  公开号：WO2009005672A1

  公开（公告）日：2009-01-08

  Azaindoles and diazaindoles having aromatic substituents on the 5-membered ring are agonists or partial agonists of the PPAR receptor and are useful in the treatment and control of type 2 diabetes and of symptoms of diabetes, including hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes.

  在5-成员环上具有芳香基团的氮杂吲哚和二氮杂吲哚是PPAR受体的激动剂或部分激动剂，并可用于治疗和控制2型糖尿病及与之常相关的高血糖、血脂异常、高脂血症、高胆固醇血症、高甘油三酯血症和肥胖症状。
• Highly functionalized 7-azaindoles as selective PPARγ modulators
  作者：Sheryl D. Debenham、Audrey Chan、Fiona WaiYu Lau、Weiguo Liu、Harold B. Wood、Karen Lemme、Lawrence Colwell、Bahanu Habulihaz、Taro E. Akiyama、Monica Einstein、Thomas W. Doebber、Neelam Sharma、Chaunlin F. Wang、Margaret Wu、Joel P. Berger、Peter T. Meinke

  DOI：10.1016/j.bmcl.2008.07.103

  日期：2008.9

  A series of highly functionalized 3-aroyl and 3-phenoxy-2-methyl-7-azaindoles have been identified, which are potent selective PPAR gamma modulators (SPPAR gamma Ms). Addition of substituents at the 6-position of the 7-azaindoles improves in vitro potency and pharmacokinetics. 7-Azaindoles have significantly improved off-target profiles compared to the parent indole series. (C) 2008 Elsevier Ltd. All rights reserved.
• A convenient one-pot synthesis of 4-, 6-, and 7-azaindoles from aminopyridines
  作者：Sheryl D. Debenham、Audrey Chan、Kun Liu、Karen Price、Harold B. Wood

  DOI：10.1016/j.tetlet.2005.02.011

  日期：2005.3

  A one-pot synthesis of a variety of substituted 4-, 6-, and 7-azaindoles from commercially available aminopyridines in moderate to good yields is described. (c) 2005 Elsevier Ltd. All rights reserved.
• Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP₂ Receptor Antagonist for Treatment of Asthma
  作者：David A. Sandham、Lucy Barker、Lyndon Brown、Zarin Brown、David Budd、Steven J. Charlton、Devnandan Chatterjee、Brian Cox、Gerald Dubois、Nicholas Duggan、Edward Hall、Julia Hatto、Janet Maas、Jodie Manini、Rachael Profit、Darren Riddy、Catherine Ritchie、Bindi Sohal、Duncan Shaw、Rowan Stringer、David A. Sykes、Matthew Thomas、Katharine L. Turner、Simon J. Watson、Ryan West、Elisabeth Willard、Gareth Williams、Jennifer Willis

  DOI：10.1021/acsmedchemlett.7b00157

  日期：2017.5.11

  Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-ypacetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.