Non-hormonal steroid modulators of NF-kB for treatment of disease

Inventors

McCall, John M. • Hoffman, Eric • Nagaraju, Kanneboyina

Assignees

Reveragen Biopharma Inc

Abstract

The present invention relates to compounds and methods which may be useful as treatments of neuromuscular diseases such as muscular dystrophy, and as inhibitors of NF-κB for the treatment or prevention of muscular wasting disease, including muscular dystrophy.

Core Innovation

The document describes non-hormonal steroid compounds that modulate NF-κB by blocking IκB phosphorylation mediated by IκB kinases (IKKs), such as IKKα and IKKβ, thereby affecting IκB phosphorylation and downstream processes involving ubiquitination and degradation of IκBs. The invention provides compounds of Formula I having specified structural features and extensive substituent definitions (R1–R9) with constraints. It also describes pharmaceutical compositions and uses for the NF-κB-modulating steroid compounds, including oral administration, pharmaceutical carriers, and unit dosage forms.

The problem being addressed is muscular wasting diseases, including muscular dystrophy, in which NF-κB is mediated. The document states that treating or preventing muscular wasting diseases is desired, with particular emphasis on muscular dystrophy subtypes such as Duchenne muscular dystrophy and Becker muscular dystrophy, and other specified muscular dystrophy types.

The partial patent content also describes chemical synthesis examples and reaction schemes for producing corticosteroid-derived esters and ketones. The disclosure includes multi-step preparations that form acetyl, oxo, and acetate functionalities on corticosteroid-derived frameworks, and it references specific synthesized products such as methyl prednisolone/prednisolone acetate and hydrocortisone acetate derivatives.

Claims Coverage

The claim set includes two independent claims. Their core inventive features center on a structural formula compound or salt thereof in an oral pharmaceutical composition, with an amount effective to treat or reduce muscular dystrophy symptoms, and in one claim the selection of specified muscular dystrophy subtypes.

Both independent claims are directed to oral pharmaceutical compositions containing a compound or salt thereof having a structural formula, with an amount effective to treat or reduce muscular dystrophy symptoms. The coverage differentiates dosing ranges and, in one claim, explicitly limits the target to a selected list of muscular dystrophy subtypes.

Stated Advantages

Documented Applications