Compounds and methods for treating lupus
Inventors
Scott, Fiona Lorraine • Taylor Meadows, Kristen R. • Peach, Robert
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11278526-B2
Publication Date
2022-03-22
Expiration Date
Abstract
Methods for treatment of systemic lupus erythematosus (SLE” or “Lupus”) by administration of a modulator of sphingosine-1-phosphate receptor subtype 1 (S1P1), as well as compositions and methods related to the same, wherein such S1P1 modulators have the following general structure and wherein X and Y are as defined herein.
Core Innovation
The invention relates to treating systemic lupus erythematosus by administering an effective amount of a compound having a specified structure, or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof. The disclosed compounds include related heterocyclic chemical structures with a common core scaffold, including a fused bicyclic or heteroaromatic system and an O–N substituted hetero-ring motif, with substituents such as cyano, amide, carboxylic acid, hydroxyl, amino, sulfonamide, and halogen groups.
The disclosure includes embodiments described by Formula I-R or Formula I-S and Formula II-R or Formula II-S, and also depicts compounds through chemical structure drawings labeled EMI-C00186 through EMI-C00203. The structures vary by side-chain chemistry, ring substituents, and stereochemical arrangement, including racemic mixtures and isolated optical isomers.
The invention is positioned as a systemic lupus erythematosus treatment using these compound embodiments as active agents. The disclosure also references S1P1 modulation, changes to SLE-associated gene expression, and preclinical SLE model readouts in NZBWF1 mice, together with therapeutic-use kits.
Claims Coverage
The claim set centers on one independent inventive concept: treating systemic lupus erythematosus by administering an effective amount of a compound having the specified structure, including pharmaceutically acceptable salt, homolog, hydrate, or solvate forms. Dependent claims add two stereochemical refinements, for a total of three inventive feature directions.
Method for treating systemic lupus erythematosus by administering a specified-structure compound
A method for treating systemic lupus erythematosus in a subject in need thereof comprising administering to the subject an effective amount of a compound having the following structure, or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof.
Racemic mixture stereochemical form
The compound is provided in the form of a racemic mixture.
Isolated optical isomer stereochemical form
The compound is provided as an isolated optical isomer.
Overall, the claims cover treating systemic lupus erythematosus by administering an effective amount of a compound defined by the specified structural formula, with further dependent coverage for either a racemic mixture or an isolated optical isomer.
Stated Advantages
Dose-dependent improvements in proteinuria in the NZBWF1 murine SLE model.
Improvements in lymphocyte subsets (CD4+, CD8+, CD19+) in the NZBWF1 murine SLE model.
Improvements in kidney lesions/TLT in the NZBWF1 murine SLE model.
Improvements in spleen parameters in the NZBWF1 murine SLE model.
Reduction or improvement of anti-dsDNA titers in the NZBWF1 murine SLE model.
Modulation of cytokine/inflammatory gene expression in the NZBWF1 murine SLE model.
Interferon-related readouts involving IFNAR1/IFNα and related signaling/inflammatory mediators are reported as improved or modulated.
Documented Applications
A method for treating systemic lupus erythematosus in a subject in need thereof by administering an effective amount of a specified-structure compound, or a pharmaceutically acceptable salt, homolog, hydrate or solvate thereof.
Use of the disclosed compounds in the NZBWF1 murine model of systemic lupus erythematosus.
Treating systemic lupus erythematosus in a subject in need thereof.
Interested in licensing this patent?