Aryl, heteroaryl, and heterocyclic compounds for treatment of immune and inflammatory disorders
Inventors
Wiles, Jason Allan • Phadke, Avinash S. • Deshpande, Milind • Agarwal, Atul • Chen, Dawei • Gadhachanda, Venkat Rao • Hashimoto, Akihiro • Pais, Godwin • Wang, Qiuping • Wang, Xiangzhu • Greenlee, William
Assignees
Medchem Discovery Consulting LLC • Achillion Pharmaceuticals Inc
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12338230-B2
Publication Date
2025-06-24
Expiration Date
Abstract
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I″ and I′″ or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
Core Innovation
The invention relates to a compound selected from a set of chemical structures, or a pharmaceutically acceptable salt thereof. The disclosed compounds are based on broad Markush-style variable substitution patterns and additional formula families, including Formula I, Formula I', Formula I'', and related formula series, together with stereochemically defined example compounds and substituted heteroaromatic, heterocycle-containing, carboxamide, and sulfonamide motifs.
The compounds include variable core scaffolds, heteroaryl and heterocycloalkyl terminology, optional substitution concepts, N-oxides, oxidized sulfur species, prodrugs, isotopic analogs, and pharmaceutically acceptable salts. The provided material also includes aryl/heteroaryl/heterocyclic small-molecule compounds that inhibit complement Factor D and are linked to Factor D inhibitor activity measurements and complement factor D-targeting lead-like small molecules.
The invention is further characterized by methods for treating or preventing complement factor D-mediated disorders by administering an effective amount to a host. The disorder lists include fatty liver, nonalcoholic steatohepatitis (NASH), liver inflammation, cirrhosis, liver failure, and multiple other inflammatory, immune, autoimmune, neurodegenerative, ocular, respiratory, cardiovascular, and CAR T-cell-related conditions.
Claims Coverage
The independent claim coverage centers on a compound selected from a set of chemical structures, or a pharmaceutically acceptable salt thereof. Across the provided items, the claims also include pharmaceutical compositions with a pharmaceutically acceptable carrier and methods of treating complement factor D-mediated disorders by administering an effective amount to a host. In total, the claim sets present three recurring inventive features.
Selected compound or pharmaceutically acceptable salt
A compound selected from a set of chemical structures, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition including a pharmaceutically acceptable carrier
A pharmaceutical composition including the compound selected from the claim set, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.
Complement factor D-mediated disorder treatment
A method of treating a complement factor D-mediated disorder by administering an effective amount of the claimed compound to a host, with narrowing to disorders including fatty liver, NASH, liver inflammation, cirrhosis, liver failure, and other listed inflammatory, immune, autoimmune, neurodegenerative, ocular, respiratory, cardiovascular, and CAR T-cell-related conditions.
Overall, the claims cover a defined family of compounds and pharmaceutically acceptable salts, their inclusion in pharmaceutical compositions with a pharmaceutically acceptable carrier, and treatment methods for complement factor D-mediated disorders.
Stated Advantages
Reduces excessive complement activation and complement cascade amplification by inhibiting complement Factor D.
Provides treatment or prevention for multiple complement-mediated and inflammatory disorders, including fatty liver, NASH, cirrhosis, liver failure, PNH, wet/dry AMD, rheumatoid arthritis, and multiple sclerosis.
Supports use in different delivery contexts, including ocular, pulmonary, and GI local delivery.
Factor D inhibitory activity is measured using an IC50 assay for non-limiting example compounds.
Documented Applications
Treating or preventing complement factor D-mediated disorders, including fatty liver, nonalcoholic steatohepatitis (NASH), liver inflammation, cirrhosis, liver failure, and other listed conditions.
Treating paroxysmal nocturnal hemoglobinuria (PNH).
Treating age-related macular degeneration (wet/dry AMD).
Treating rheumatoid arthritis.
Treating multiple sclerosis.
Treating dermatomyositis, amyotrophic lateral sclerosis, C3 glomerulonephritis, retinal degeneration, ophthalmic disease, respiratory disease, cardiovascular disease, and inflammatory reactions to biotherapeutics including CAR T-cell therapy.
Use in ocular, pulmonary, and GI local delivery contexts.
Use in combination contexts that include adoptive cell transfer/CAR T-cell therapy.
Use in prophylaxis contexts with prophylactic antibiotics/vaccines during complement inhibition.
Use of a pharmaceutical composition including the claimed compound, or a pharmaceutically acceptable salt, together with a pharmaceutically acceptable carrier.
Interested in licensing this patent?