3-[2-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methylamino]-3-pyridyl]prop-2-yn-1-ol | 2092997-91-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-[2-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methylamino]-3-pyridyl]prop-2-yn-1-ol
• 英文别名: 3-[2-[[[4-(methylsulfonyl)-2-(trifluoromethyl)phenyl]methyl]amino]-3-pyridinyl]-2-propyn-1-ol；3-(2-((4-(Methylsulfonyl)-2-(trifluoromethyl)benzyl)amino)pyridin-3-YL)prop-2-YN-1-OL；3-[2-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methylamino]pyridin-3-yl]prop-2-yn-1-ol
• CAS: 2092997-91-4
• 化学式: C₁₇H₁₅F₃N₂O₃S
• 分子量: 384.379
• InChiKey: KKSUBNRZGIEHBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-[2-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methylamino]-3-pyridyl]prop-2-yn-1-ol 在 溶剂黄146 、 4-甲基-2-戊酮 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 非维匹仑
  参考文献：
  名称：

  Fevipiprant. Selective prostaglandin DP2 (CRTh2) inhibitor, Treatment of asthma

  摘要：

  Prostaglandin D-2 (PGD(2)), a major prostanoid, releases from activated mast cells. It activates and recruits various inflammatory cells like eosinophils and basophils through DP2 receptors to the site of inflammation and further promotes late-phase allergic reactions. For the last decade, the scientific community has extensively explored this pathway and synthesized various specific DP2 receptor antagonists for the management of asthma. About 20 compounds with DP2 antagonistic activity have reached different stages of clinical development. Among these, fevipiprant is one of the most advanced oral DP2 inhibitors as it selectively blocks the DP2 receptors. Fevipiprant has demonstrated an acceptable safety profile in phase II studies as evident from significant reduction of moderate to severe asthma exacerbations. Currently this novel antiasthmatic drug is in phase III clinical trials. This review provides a brief overview of PGD(2) blockers, particularly fevipiprant and its preclinical pharmacology and clinical development, by providing a summary of completed or ongoing clinical studies assessing its safety and efficacy in asthma.

  DOI：

  10.1358/dof.2018.043.08.2832262
• 作为产物：
  描述：

  2,3-二溴吡啶 在 bis(acetylacetonato)palladium(II) 、 copper(l) iodide 、 palladium diacetate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 苯甲醚 、 三苯基膦 作用下， 以 乙醇 为溶剂， 生成 3-[2-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl]methylamino]-3-pyridyl]prop-2-yn-1-ol
  参考文献：
  名称：

  Fevipiprant. Selective prostaglandin DP2 (CRTh2) inhibitor, Treatment of asthma

  摘要：

  Prostaglandin D-2 (PGD(2)), a major prostanoid, releases from activated mast cells. It activates and recruits various inflammatory cells like eosinophils and basophils through DP2 receptors to the site of inflammation and further promotes late-phase allergic reactions. For the last decade, the scientific community has extensively explored this pathway and synthesized various specific DP2 receptor antagonists for the management of asthma. About 20 compounds with DP2 antagonistic activity have reached different stages of clinical development. Among these, fevipiprant is one of the most advanced oral DP2 inhibitors as it selectively blocks the DP2 receptors. Fevipiprant has demonstrated an acceptable safety profile in phase II studies as evident from significant reduction of moderate to severe asthma exacerbations. Currently this novel antiasthmatic drug is in phase III clinical trials. This review provides a brief overview of PGD(2) blockers, particularly fevipiprant and its preclinical pharmacology and clinical development, by providing a summary of completed or ongoing clinical studies assessing its safety and efficacy in asthma.

  DOI：

  10.1358/dof.2018.043.08.2832262

文献信息

• Using a Johnson‐Claisen Rearrangement Strategy to Construct Azaindoles – A Streamlined and Concise Route for the Commercial Process of Fevipiprant
  作者：Christian Mathes、Bernard Riss、Ueli Rüegger、Lukas Hueber、Darija Dedic、Zhongbo Fei、Carolien Reijer、Kurt Königsberger、Matthias Napp、Thierry Schlama、Glen Dempsey、Philipp Lustenberger

  DOI：10.1002/ejoc.202100686

  日期：2021.8.20

  novel and concise synthesis of the DP2 receptor antagonist Fevipiprant (NVP-QAW039) was developed. The key step – a Johnson Claisen reaction followed by an intramolecular hydroamination of the formed reactive allene moiety allowed to build the 7-aza-indole framework, while overcoming the low selectivity and low yield of the initial research route, and give access to a commercially viable process with a

  开发了 DP2 受体拮抗剂 Fevipiprant (NVP-QAW039) 的新颖简洁的合成方法。关键步骤——Johnson Claisen 反应，然后对形成的反应性丙二烯部分进行分子内加氢胺化，从而构建 7-氮杂-吲哚骨架，同时克服了最初研究路线的低选择性和低产率，并提供了商业途径生态足迹减少的可行过程。
• Process for preparing 1-(4-methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo [2,3-B]pyridin-3-yl-acetic acid
  申请人：Lustenberger Philipp

  公开号：US10508110B2

  公开（公告）日：2019-12-17

  This invention relates to novel processes for synthesizing [1-(4-Methanesulfonyl-2-trifluoromethyl-benzyl)-2-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl]-acetic acid and to intermediates that are used in such processes.

  本发明涉及合成[1-(4-甲磺酰基-2-三氟甲基-苄基)-2-甲基-1H-吡咯并[2,3-b]吡啶-3-基]-乙酸的新工艺以及用于此类工艺的中间体。
• PROCESS FOR PREPARING 1-(4-METHANESULFONYL-2-TRIFLUOROMETHYL-BENZYL)-2-METHYL-1H-PYRROLO [2,3-B]PYRIDIN-3-YL-ACETIC ACID
  申请人：Novartis AG

  公开号：EP3356329A1

  公开（公告）日：2018-08-08