Pharmaceutical compounds for treatment of medical 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 • Barrish, Joel Charles • Greenlee, William • Eastman, Kyle J.
Assignees
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Publication Number
US-12006307-B2
Publication Date
2024-06-11
Expiration Date
Abstract
Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, and Formula IV or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
Core Innovation
The disclosure provides structurally defined compounds of Formula I, Formula II, Formula III, Formula IV, Formula IA to Formula ID, and related variants, including pharmaceutically acceptable salts, prodrugs, isotopic analogs, N-oxides, solvates, and isomers. The compound families include heteroaromatic, heterocyclic, amide, carbonyl, carboxylic acid, phosphonate, phosphonic acid, phosphinate, sulfonamide, carbamate, boron-containing, and phosphate/phosphonate-containing motifs, with ring systems such as azabicyclohexane, indazole, pyridine, pyrimidine, quinazoline-like, pyrazole, thieno-like, and fused heteroaromatic or bicyclic scaffolds.
The disclosed embodiments emphasize variable substituents, including R groups, B/B3/B4, B/L linkers, L, m, stereochemical markers, halogens, alkyl, cycloalkyl, heteroaryl, heterocycle, amino, amide, and optional ring substitutions. Representative embodiments are presented through enumerated formula sets and example structures that define different members of the same general compound class, including stereodefined compounds and other defined structural variants within the same compound space.
The invention is linked to complement Factor D-mediated disorders and complement pathway mediated disorders. The disclosed compounds are described as being administered in an effective amount to a subject for treating such disorders, and the claim context also includes pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier.
Claims Coverage
The consolidated claim coverage centers on structurally defined compounds, with independent claim families directed to a compound of a specified structure or a pharmaceutically acceptable salt thereof. One claim family further includes pharmaceutical compositions and methods for treating complement Factor D-mediated disorders by administering an effective amount, with additional limitations to human subjects and enumerated disorder selections. Across the inputs, the inventive coverage is primarily structural, with therapeutic and formulation coverage added in the dependent claims.
Compound of specified structure and pharmaceutically acceptable salt
A compound of a specified structure, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition including pharmaceutically acceptable carrier
A pharmaceutical composition including the compound and a pharmaceutically acceptable carrier.
Treatment of complement Factor D-mediated disorders by administration
A method for treating a complement Factor D-mediated disorder by administering to a subject an effective amount of the compound or a pharmaceutically acceptable salt thereof.
Human subject treatment
The method is carried out with a human as the subject.
Disorder selection from an enumerated list
The disorder treated is selected from a specified list of multiple acute and chronic diseases and conditions.
Disorder selection from a narrower subset
The disorder treated is selected from age-related macular degeneration, C3 glomerulonephritis, dense deposit disease, geographic atrophy, IgA nephropathy, lupus nephritis, myasthenia gravis, paroxysmal nocturnal hemoglobinuria, reduced glomerular filtration rate, a renovascular disorder, or sickle cell disease.
Overall, the claims center on defined compound structures and their pharmaceutically acceptable salts. The therapeutic claim family further covers pharmaceutical compositions and methods of treating complement Factor D-mediated disorders by administration of an effective amount, with further restriction to human subjects and enumerated disorder sets.
Stated Advantages
Treating a complement Factor D-mediated disorder by administration of an effective amount of the structurally defined compound or its pharmaceutically acceptable salt.
Documented Applications
Treatment of complement pathway mediated disorders, including complement Factor D-mediated disorders.
Treatment of complement Factor D-mediated disorders by administering an effective amount of the claimed compound or a pharmaceutically acceptable salt thereof to a subject.
Pharmaceutical compositions including the disclosed compound or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.
Treatment examples explicitly listed include fatty liver/nonalcoholic steatohepatitis (NASH), liver inflammation, cirrhosis, liver failure, dermatomyositis, amyotrophic lateral sclerosis, paroxysmal nocturnal hemoglobinuria, rheumatoid arthritis, multiple sclerosis, age-related macular degeneration, geographic atrophy, C3 glomerulonephritis, dense deposit disease, IgA nephropathy, lupus nephritis, myasthenia gravis, reduced glomerular filtration rate, renovascular disorder, sickle cell disease, and other ophthalmic, respiratory, and cardiovascular diseases.
Use in humans and for disorders selected from enumerated acute and chronic disease lists.
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