N-[(3R)-1,3-bis(butoxymethyl)-7-fluoro-1-methyl-3,4-dihydro-[1,4]oxazino[4,3-a]indol-8-yl]-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: N-[(3R)-1,3-bis(butoxymethyl)-7-fluoro-1-methyl-3,4-dihydro-[1,4]oxazino[4,3-a]indol-8-yl]-1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxamide
• 化学式: C₃₃H₃₉F₃N₂O₆
• 分子量: 616.7
• InChiKey: AXNOVTRZWZQSFV-WNEYBHKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  80.2
• 氢给体数：
  1
• 氢受体数：
  9

文献信息

• Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150231142A1

  公开（公告）日：2015-08-20

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及含有上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
  申请人：Van Goor Fredrick F.

  公开号：US20110098311A1

  公开（公告）日：2011-04-28

  The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

  本发明涉及包含上皮钠通道活性抑制剂与至少一种ABC转运蛋白调节剂化合物（A式、B式、C式或D式）的药物组合物。该发明还涉及这些药物配方，以及使用这些组合物治疗CFTR介导的疾病，特别是囊性纤维化的方法。
• Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof
  申请人：Vertex Pharmaceuticals Incorported

  公开号：US20140088160A1

  公开（公告）日：2014-03-27

  A pharmaceutical composition comprising Compound 1, (R)-1-(2,2-difluorobenzo[d][1,3]dioxo-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide, and at least one excipient selected from: a filler, a disintegrant, a surfactant, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering the pharmaceutical composition of Compound 1 are also disclosed.

  一种药物组合物，包括化合物1，(R)-1-(2,2-二氟苯并[d][1,3]二氧杂环-5-基)-N-(1-(2,3-二羟基丙基)-6-氟-2-(1-羟基-2-甲基丙烷-2-基)-1H-吲哚-5-基)环丙烷羧酰胺，以及至少一种所选的赋形剂，包括填充剂、崩解剂、表面活性剂、流动剂和润滑剂，该组合物适用于口服给予需要治疗CFTR介导疾病，如囊性纤维化的患者。本文还公开了治疗需要者的方法，包括给予化合物1的药物组合物。
• Solid Forms of (R)-1(2,2-Difluorobenzo[D][1,3]Dioxol-5-yl)-N-(1-(2,3-Dihydroxypropyl)-6-Fluoro-2-(1-Hydroxy-2-Methylpropan-2-yl)-1H-Indol-5-yl)Cyclopropanecarboxamide
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150203478A1

  公开（公告）日：2015-07-23

  The present invention relates to solid forms of (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) in substantially crystalline form (Form A) or amorphous form, pharmaceutical compositions thereof, and methods of treatment therewith.

  本发明涉及(R)-1-(2,2-二氟苯并[d][1,3]二氧戊基-5-基)-N-(1-(2,3-二羟基丙基)-6-氟-2-(1-羟基-2-甲基丙基)-1H-吲哚-5-基)环丙烷羧酰胺(化合物1)的固态形式，包括实质晶体形式（A形式）或非晶形式，以及其制备的制药组合物和治疗方法。
• Pharmaceutical Compositions of (R)-1-(2,2-Difluorobenzo[D] [1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarbox-amide and Administration Thereof
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20170266176A1

  公开（公告）日：2017-09-21

  A pharmaceutical composition comprising Compound 1, (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide, and at least one excipient selected from: a filler, a disintegrant, a surfactant, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering the pharmaceutical composition of Compound 1 are also disclosed.