Pyridazinone compounds and uses thereof
Inventors
Hunt, Kevin • Koch, Kevin • Russell, Alan • Schlachter, Stephen • Winship, Paul • UZOHO, Grace • Steele, Chris
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12240833-B2
Publication Date
2025-03-04
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 a neuromuscular condition by administering to a patient in need thereof a compound represented by Formula (I), or a salt thereof. The claimed compounds provide specified alternatives for ring atoms and substituents, wherein at least one X is N, N-oxide, or N⁺(—O⁻). The disclosure also describes pyridazinone compounds, including Formula (III) and Formula (III′), as selective inhibitors of fast-fiber skeletal muscle myosin II.
The therapeutic objective is to reduce excessive skeletal-muscle contraction, contraction-related muscle damage, and contraction-induced injury. This targeted inhibition aims to preserve physical function, daily activity, and respiratory function while limiting effects on cardiac muscle contraction. Compounds undergo evaluation in skeletal and cardiac myofibril ATPase assays and an mdx mouse tibialis-anterior injury assay, while background and problem details are omitted.
Tables disclose pyridazin-3(2H)-one compounds comprising substituted pyridyl or pyrimidinyl groups, varied benzyl substituents, and substituted aryl analogues. Selected compounds are characterized by mass spectrometry and NMR spectroscopy, with related Formula (II), Formula (II′), Formula (III), and Formula (III′) compounds identified alongside isotopic, stereoisomeric, tautomeric, salt, and prodrug forms.
Claims Coverage
The claims identify one independent claim directed to a method of treating a neuromuscular condition, presenting three inventive features.
Treatment of a neuromuscular condition
A method of treating a neuromuscular condition by administering a compound represented by Formula (I), or a salt thereof, to a patient in need thereof.
Formula (I) compound or salt structure
The administered compound is represented by Formula (I) or is a salt thereof, wherein each X is independently selected from C(R3), N, and N-oxide, with at least one X being N, N-oxide, or N⁺(—O⁻).
Substituent and ring alternatives
Formula (I) provides specified alternatives for A and R groups, including optionally substituted alkyl, alkenyl, alkynyl, carbocycle, and heterocycle groups, as well as ring-forming combinations of specified substituents.
Claim 1 combines the treatment of a neuromuscular condition with administration of a structurally defined Formula (I) compound or salt, with dependent claims narrowing substituent options, parameter values, ring formations, and selected compound structures.
Stated Advantages
The stated aim is to reduce excessive skeletal-muscle contraction, muscle damage, and contraction-induced injury.
Selective fast-fiber skeletal muscle myosin inhibition aims to preserve physical function, daily activity, and respiratory function while limiting effects on cardiac muscle contraction.
Documented Applications
Treatment of a neuromuscular condition, including Duchenne muscular dystrophy, muscular dystrophies, and spasticity, by administering a Formula (I) compound or salt to a patient in need thereof.
Treatment of movement disorders.
Treatment of activity-induced muscle damage.
Evaluation of compounds in skeletal and cardiac myofibril ATPase assays and an mdx mouse tibialis-anterior injury assay.
Interested in licensing this patent?