N-(3-carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-2-oxopyrrolidine-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡喃类
• 英文名称: N-(3-carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-2-oxopyrrolidine-3-carboxamide
• 英文别名: N-(3-carbamoyl-5,5,7,7-tetramethyl-4H-thieno[2,3-c]pyran-2-yl)-2-oxopyrrolidine-3-carboxamide
• 化学式: C₁₇H₂₃N₃O₄S
• 分子量: 365.453
• InChiKey: HQQVWXRSXAVQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二甲基-2,5-庚二烯-4-酮 在 盐酸 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 4-二甲氨基吡啶 、 2-氯-1-甲基吡啶碘化物 、 二乙胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 160.0h， 生成 N-(3-carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-2-oxopyrrolidine-3-carboxamide
  参考文献：
  名称：

  Discovery of N-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-lH-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent

  摘要：

  Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators). Here we describe the discovery of a novel potentiator GLPG1837, which shows enhanced efficacy on CFTR mutants harboring class III mutations compared to Ivacaftor, the first marketed potentiator. The optimization of potency, efficacy, and pharmacokinetic profile will be described.

  DOI：

  10.1021/acs.jmedchem.7b01288

文献信息

• [EN] THIENO[2,3-C]PYRANS AS CFTR MODULATORS<br/>[FR] THIÉNO [2,3-C] PYRANNES UTILISÉS EN TANT QUE MODULATEURS DU CFTR
  申请人：GALAPAGOS NV

  公开号：WO2015018823A1

  公开（公告）日：2015-02-12

  The present invention discloses compounds according to Formula I: Wherein R is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.

  本发明公开了根据式I的化合物：其中R如本文所定义。本发明涉及化合物及其在囊性纤维化治疗中的应用，其生产方法，包含相同化合物的药物组合物，以及通过给予本发明化合物治疗囊性纤维化的方法。
• NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF CYSTIC FIBROSIS
  申请人：Galapagos NV

  公开号：US20150045327A1

  公开（公告）日：2015-02-12

  The present invention discloses compounds according to Formula I: wherein R 1 is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.

  本发明揭示了符合以下式I的化合物：其中R1如本文所定义。本发明涉及化合物及其在囊性纤维化治疗中的应用，其生产方法，包含相同化合物的药物组合物，以及通过给予本发明化合物治疗囊性纤维化的方法。
• Compounds and pharmaceutical compositions thereof for the treatment of cystic fibrosis
  申请人：GALAPAGOS NV

  公开号：US10568867B2

  公开（公告）日：2020-02-25

  The present invention discloses compounds according to Formula I: wherein R1 is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.

  本发明公开了符合式 I 的化合物： 其中 R1 如本文所定义。本发明涉及治疗囊性纤维化的化合物及其用途、生产方法、包含本发明化合物的药物组合物，以及通过施用本发明化合物治疗囊性纤维化的方法。
• THIENO[2,3-C]PYRANS AS CFTR MODULATORS
  申请人：Galapagos NV

  公开号：EP3030568B1

  公开（公告）日：2018-09-19
• Novel Compounds and Pharmaceutical Compositions Thereof for the Treatment of Cystic Fibrosis
  申请人：Galapagos NV

  公开号：US20160317493A1

  公开（公告）日：2016-11-03

  The present invention discloses compounds according to Formula I: wherein R 1 is as defined herein. The present invention relates to compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment cystic fibrosis by administering a compound of the invention.