Pyridazinone compounds and uses thereof
Inventors
Hunt, Kevin • Koch, Kevin • Russell, Alan • Schlachter, Stephen • Winship, Paul • Steele, Chris • UZOHO, Grace
Assignees
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Publication Number
US-12415794-B2
Publication Date
2025-09-16
Expiration Date
Abstract
Substituted pyridazinone compounds, conjugates, and pharmaceutical compositions for use in the treatment of neuromuscular diseases, such as Duchenne Muscular Dystrophy (DMD), are disclosed herein. The disclosed compounds are useful, among other things, in the treating of DMD and modulating inflammatory inhibitors IL-1, IL-6 or TNF-α.
Core Innovation
The independent claim describes a method of treating activity-induced muscle damage, a neuromuscular condition, or a movement disorder by administering a compound of Formula (III′), or a salt thereof. These compounds function as selective fast skeletal muscle (type II) myosin II inhibitors that reduce excessive skeletal muscle contractions and muscle damage. The disclosure describes substituted pyridazinone acetamide compounds, including 6-oxopyridazinyl acetamide derivatives with diverse aryl, heteroaryl, and amide N-substituents across defined structural formulas.
Selective inhibition limits adverse effects on cardiac, slow-type I, smooth, and respiratory muscle while preserving daily activity and function. Documented assessment contexts identify skeletal and cardiac myofibril ATPase counter-screen assays and an mdx-mouse tibialis anterior injury model measuring force changes and muscle mass. Because the background section is omitted from the provided content, the background problem being addressed is not explicitly described in patent.
Claims Coverage
The provided claims identify one independent claim comprising one inventive feature directed to a treatment method using a compound of Formula (III′) or a salt thereof.
Treatment using a compound of Formula (III′)
A method of treating activity-induced muscle damage, a neuromuscular condition, or a movement disorder, comprising administering to a subject in need thereof a compound of Formula (III′), or a salt thereof, with structural variables defined in the claim.
The independent claim covers administration of a defined compound of Formula (III′) or a salt thereof to treat activity-induced muscle damage, a neuromuscular condition, or a movement disorder, with dependent claims further reciting specific neuromuscular conditions, additional therapeutic agents, and an efficacy threshold for reducing involuntary muscle contractions.
Stated Advantages
Selective inhibition reduces excessive skeletal muscle contractions and contraction-induced muscle injury.
Selective inhibition limits adverse effects on cardiac, slow-type I, smooth, and respiratory muscle while preserving daily activity and function.
A dependent claim specifies an administered amount sufficient to reduce involuntary muscle contractions by at least 10%.
Documented Applications
Treatment of activity-induced or contraction-induced muscle damage.
Treatment of neuromuscular conditions, including Duchenne muscular dystrophy, Becker muscular dystrophy, myotonic dystrophy 1 and 2, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, limb girdle muscular dystrophy, tendinitis, and carpal tunnel syndrome.
Treatment of movement disorders, including spasticity.
Combination treatment alongside an additional therapeutic agent, including deflazacort, prednisone, or gene therapy comprising the dystrophin gene or a variant or truncated version thereof.
Experimental assessment contexts including an mdx-mouse tibialis anterior injury model and skeletal and cardiac myofibril ATPase counter-screen assays.
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