Drugs and compositions for the treatment of ocular disorders

Inventors

Yang, Ming • Bauman, John G. • Cleland, Jeffrey L. • Hoang, Nu • Cunningham, Emmett

Assignees

Calcimedica Inc

Abstract

The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.

Core Innovation

The disclosure relates to a compound of a specified formula, or a pharmaceutically acceptable salt thereof, in which x and x2 are 1 and y and y2 are selected from 2, 3, 4, 5, and 6. The disclosed structures include multiple formula embodiments, stereochemical variants, and example compounds presented as concrete chemical structures within the same general scaffold.

The disclosure further describes prodrug and linker strategies, including covalently linked prodrugs, ester/amide/linker motifs, biodegradable polymeric delivery forms, polymer-linked substituents, polymer-controlled delivery, biodegradable polymer blends, polymer moieties, particles, microparticles, and nanoparticles with polymeric core and surface-coating systems. Representative embodiments mention prostaglandin-, brimonidine-, timolol-, brinzolamide-, dorzolamide-, acetazolamide-, methazolamide-, sunitinib-, and other kinase or RKI inhibitor-related structures, together with PEG, PLGA, polylactic acid, polyglycolic acid, polyester, and polyamide classes.

The described chemical space also includes substituted heteroaromatic and heterocyclic motifs, hydrophobic moieties, brominated and other halogenated motifs, fused ring systems, esterase-mediated hydrolysis concepts, E and Z isomeric forms, late-stage esterification and coupling-derived intermediates, and prodrug forms intended to be metabolized to release parent therapeutics. Additional embodiments refer to ocular prodrug concepts and sustained or controlled ocular delivery.

Claims Coverage

The independent claim coverage centers on one compound-of-a-formula framework with two fixed parameters and one enumerated parameter set: x and x2 are fixed at 1, and y and y2 are each selected from 2, 3, 4, 5, and 6. Across the provided claim set, the inventive scope is narrowed in dependent claims to specific y/y2 pairings within that enumerated range.

Overall, the claims are directed to formula-defined compounds or pharmaceutically acceptable salts with x and x2 fixed at 1 and y and y2 selected from an enumerated set, with dependent claims further restricting the scope to specific y/y2 combinations.

Stated Advantages

Documented Applications