Compositions and therapeutic methods for the treatment of complement-associated diseases
Inventors
Kulikowski, Ewelina B. • Gilham, Dean E. • Wasiak, Sylwia • Halliday, Christopher R. A. • Hansen, Henrik C.
Assignees
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Publication Number
US-10772894-B2
Publication Date
2020-09-15
Expiration Date
Abstract
The invention comprises methods of modulating the complement cascade in a mammal and for treating and/or preventing diseases and disorders associated with the complement pathway by administering a compound of Formula I or Formula II, such as, for example, 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one or a pharmaceutically acceptable salt thereof.
Core Innovation
The invention relates to complement-modulating quinazolinone compounds of Formula I and Formula II. The disclosed compounds include stereoisomers, tautomers, pharmaceutically acceptable salts, and hydrates, with broad derivative and formulation scope including solvates/polymorphs and optional prodrugs.
The invention addresses complement-associated diseases associated with aberrant complement activity by providing complement-modulating compounds for treating or preventing such diseases. The documented disease associations include atherosclerosis, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), IgA nephropathy, and hereditary angioedema (HAE).
The disclosure further describes relevance of the complement-modulating effect through figure descriptions indicating reduced complement component expression or secretion for complement component 3 (C3), complement component 4 (C4), and complement component 5 (C5). Complement activity reduction is indicated using AH50 and CH50 assays, including an example associated with RVX000222.
Claims Coverage
The document contains one independent claim that defines a compound selection and includes additional scope for stereoisomers, tautomers, pharmaceutically acceptable salts, and hydrates. Dependent claims specify named compound members and add pharmaceutical composition coverage with a pharmaceutically acceptable carrier. Overall, the inventive features focus on specific complement-modulating quinazolinone structures and their pharmaceutical compositions.
Selected quinazolinone compound with defined substituents
A compound selected from 2-{4-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]-3,5-dimethylphenyl}-5,7-dimethoxy-3,4-dihydroquinazolin-4-one; methyl N-{2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]ethyl}carbamate; and stereoisomers, tautomers, pharmaceutically acceptable salts, and hydrates thereof.
Named compound member defined by full substitution pattern
The compound is defined as 2-{4-[2-(3,3-difluoropyrrolidin-1-yl)ethoxy]-3,5-dimethylphenyl}-5,7-dimethoxy-3,4-dihydroquinazolin-4-one.
Named carbamate compound member
The compound is defined as methyl N-{2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]ethyl}carbamate.
Pharmaceutical composition including the selected quinazolinone compound
A pharmaceutical composition that includes the compound from the selected compound definition together with a pharmaceutically acceptable carrier.
Pharmaceutical composition including the specific compound member
A pharmaceutical composition is provided that includes the named substitution-pattern member together with a pharmaceutically acceptable carrier.
Pharmaceutical composition including the carbamate compound member
A pharmaceutical composition is claimed that includes the named carbamate member together with a pharmaceutically acceptable carrier.
The claim set is directed to specific complement-modulating quinazolinone compound selections and their stereoisomeric, tautomeric, and salt or hydrate forms. The coverage additionally extends to pharmaceutical compositions comprising the selected compounds with a pharmaceutically acceptable carrier.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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