Methods for treating Crohn's disease using 3-((1R,3s,5S)-3-((7-((5-methyl-1H-pyrazol-3-yl)amino)-1,6-naphthyridin-5-yl)amino)-8-azabicyclo[3.2.1]octan-8-yl)propanenitrile
Inventors
Hudson, Ryan • Kozak, Jennifer • Podesto, Dante D. • Huang, Xiaojun • Thalladi, Venkat R.
Assignees
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Publication Number
US-11780852-B2
Publication Date
2023-10-10
Expiration Date
Abstract
Disclosed are methods for treating Crohn's disease using a compound of the formula: or a pharmaceutically-acceptable salt thereof.
Core Innovation
The disclosure relates to methods for treating Crohn's disease and other gastrointestinal inflammatory diseases in a mammal or human using substituted 1,6-naphthyridine-5,7-diamine JAK inhibitors bearing 5-methylpyrazole and azabicyclic groups. The specified compound inhibits JAK1, JAK2, JAK3, and TYK2, providing high gastrointestinal exposure with limited systemic absorption. Administration encompasses the specified compound, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a pharmaceutically acceptable carrier, including oral administration to humans.
The disclosure further describes solid forms of the compound, including crystalline Form I characterized by powder X-ray diffraction peaks and differential scanning calorimetry, alongside solvate Form II. Pharmaceutical compositions, unit dosage forms, and optional combination therapies are provided for oral delivery. Biological evaluations demonstrate cellular potency, oxazolone-induced anti-colitic activity, favorable colon exposure, and limited systemic immunosuppression in recipient subjects.
Claims Coverage
The nine independent claims cover methods for treating Crohn's disease using the specified compound, pharmaceutical compositions containing it, oral administration regimens, and specified crystalline forms.
Treatment using the specified compound or salt
Independent claim 1 covers treating Crohn's disease in a mammal by administering a therapeutically effective amount of the specified compound or a pharmaceutically acceptable salt thereof.
Treatment using a pharmaceutical composition comprising the compound or salt
Independent claim 5 covers treating Crohn's disease in a mammal by administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the specified compound or a pharmaceutically acceptable salt thereof.
Oral treatment using a pharmaceutical composition comprising the compound or salt
Independent claim 13 covers treating Crohn's disease in a human by orally administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the specified compound or a pharmaceutically acceptable salt thereof.
Treatment using the specified compound
Independent claim 22 covers treating Crohn's disease in a mammal by administering a therapeutically effective amount of the compound of the recited formula.
Treatment using a pharmaceutical composition containing the compound
Independent claim 23 covers treating Crohn's disease in a mammal by administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of the recited formula.
Oral treatment using a pharmaceutical composition containing the compound
Independent claim 28 covers treating Crohn's disease in a human by orally administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of the recited formula.
Treatment using a crystalline form characterized by diffraction peaks
Independent claim 33 covers treating Crohn's disease in a mammal using a crystalline form of the compound characterized by powder X-ray diffraction peaks at 7.87 , 12.78 , 15.78 , and 20.41 2θ, with recited tolerances.
Treatment using a composition containing the crystalline form
Independent claim 38 covers treating Crohn's disease in a mammal using a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline form of the compound characterized by powder X-ray diffraction peaks at 7.87 ±0.20 , 12.78 ±0.20 , 15.78 ±0.20 , and 20.41 ±0.20 2θ.
Oral treatment using a composition containing the crystalline form
Independent claim 47 covers treating Crohn's disease in a human by oral administration of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline form of the compound characterized by powder X-ray diffraction peaks at 7.87 ±0.20 , 12.78 ±0.20 , 15.78 ±0.20 , and 20.41 2θ, with recited tolerances.
The independent claims cover compound-based treatment, carrier-containing pharmaceutical compositions, oral administration to humans, and treatment using crystalline forms defined by powder X-ray diffraction characteristics.
Stated Advantages
The compounds provide high gastrointestinal exposure with limited systemic absorption.
Preclinical findings report anti-colitic activity with minimal systemic immunosuppression.
Crystalline Form I exhibits low hygroscopicity and stability under accelerated conditions.
Documented Applications
Treatment of Crohn's disease in a mammal or human, including via oral administration.
Treatment of other gastrointestinal inflammatory diseases.
Oral pharmaceutical compositions, unit dosage forms, and optional combination therapies.
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