US2023331712A1PendingUtilityA1

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

82
Assignee: VERTEX PHARMAPriority: Mar 25, 2010Filed: Nov 22, 2022Published: Oct 19, 2023
Est. expiryMar 25, 2030(~3.7 yrs left)· nominal 20-yr term from priority
Inventors:Ali Keshavarz-ShokriBeili ZhangTim Edward AlcacioElaine Chungmin LeeYuegang ZhangMariusz Krawiec
C07D 405/12A61K 31/404A61K 45/06A61K 31/47A61K 31/4709C07B 2200/13
82
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
1 .- 80 . (canceled) 
     
     
         81 . Crystalline Form A 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, characterized by a differential scanning calorimetry trace substantially similar to that of  FIG.  6   . 
     
     
         82 . Crystalline Form A 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, characterized by a solid state  13 C NMR spectrum with at least one peak selected from 175.3, 155.4, 153.3, 144.3, 143.7, 143.0, 139.0, 135.8, 128.2, 123.3, 120.0, 115.8, 114.9, 111.3, 102.8, 73.8, 69.8, 64.5, 51.6, 39.1, 30.5, 26.8, 24.4, 16.3, and 15.8. 
     
     
         83 . Crystalline Form A of  claim 82 , characterized by a solid state  13 C NMR spectrum substantially similar to that of  FIG.  11   . 
     
     
         84 . Crystalline Form A 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, characterized by a solid state  19 F NMR spectrum with at least one peak selected from −45.9, −51.4, −53.3, −126.5, and −128.4. 
     
     
         85 . Crystalline Form A of  claim 84 , characterized by a solid state  19 F NMR spectrum substantially similar to that of  FIG.  12   . 
     
     
         86 . Crystalline Form A of  claim 81 , prepared by a process comprising a slurry method, a slow evaporation method, a fast evaporation method, or an anti-solvent method. 
     
     
         87 . Crystalline Form A of  claim 82 , prepared by a process comprising a slurry method, a slow evaporation method, a fast evaporation method, or an anti-solvent method. 
     
     
         88 . Crystalline Form A of  claim 83 , prepared by a process comprising a slurry method, a slow evaporation method, a fast evaporation method, or an anti-solvent method. 
     
     
         89 . Crystalline Form A of  claim 84 , prepared by a process comprising a slurry method, a slow evaporation method, a fast evaporation method, or an anti-solvent method. 
     
     
         90 . Crystalline Form A of  claim 85 , prepared by a process comprising a slurry method, a slow evaporation method, a fast evaporation method, or an anti-solvent method. 
     
     
         91 . A pharmaceutical composition comprising crystalline Form A of  claim 81 . 
     
     
         92 . A pharmaceutical composition comprising crystalline Form A of  claim 82 . 
     
     
         93 . A pharmaceutical composition comprising crystalline Form A of  claim 83 . 
     
     
         94 . A pharmaceutical composition comprising crystalline Form A of  claim 84 . 
     
     
         95 . A pharmaceutical composition comprising crystalline Form A of  claim 85 . 
     
     
         96 . A solid dispersion comprising amorphous (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, prepared by a process comprising converting crystalline Form A 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 into an amorphous form. 
     
     
         97 . The solid dispersion of  claim 96 , wherein the crystalline Form A is spray-dried. 
     
     
         98 . A pharmaceutical composition comprising the solid dispersion of  claim 96  and a pharmaceutically acceptable carrier. 
     
     
         99 . A pharmaceutical composition comprising the solid dispersion of  claim 97  and a pharmaceutically acceptable carrier. 
     
     
         100 . A method of treating cystic fibrosis comprising administering crystalline Form A of  claim 81 . 
     
     
         101 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of crystalline Form A of  claim 82 . 
     
     
         102 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of crystalline Form A of  claim 83 . 
     
     
         103 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of crystalline Form A of  claim 84 . 
     
     
         104 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of crystalline Form A of  claim 85 . 
     
     
         105 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of the solid dispersion of  claim 96 . 
     
     
         106 . A method of treating cystic fibrosis in a subject comprising administering to the subject an effective amount of the solid dispersion of  claim 97 .

Join the waitlist — get patent alerts

Track US2023331712A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.