Antiviral use of FABP4 modulating compounds
Inventors
Koyuncu, Emre • Kim, Hahn • Hotamisligil, Gokhan
Assignees
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Publication Number
US-12138243-B2
Publication Date
2024-11-12
Expiration Date
Abstract
A method for treating a viral disease in a subject comprising administering to said subject a therapeutically effective dose of one or more compounds that bind to fatty acid binding protein FABP4, with compounds described in the specification some having the general formula, Formula I-Formula XII, where W1-W4, Z1-Z4, Z1-Z5, X, Y, n, and R1-R5 are as defined in the claims and description of embodiments. In examples, the ring Z contains Z1-Z4. In other examples, the ring Z contains Z1-Z5.
Core Innovation
The invention relates to isotopically labeled analogs of compounds, including compounds labeled with 2H, 3H, 11C, 13C, 14C, 15N, 18O, 17O, 31P, 32P, 35S, and 18F, as well as radioactive forms such as 36Cl and 125I. These isotopically labeled analogs are provided for metabolic, reaction kinetic studies, and detection/imaging studies, and utility is stated in PET and SPECT, as well as in drug/substrate tissue distribution assays and radioactive treatment.
The document further recites that salts, solvates, polymorphs, and prodrugs apply to stereochemical variants, including enantiomers, stereoisomers, rotamers, tautomers, and atropisomers. The scope expressly includes racemates, and pharmaceutically relevant stereochemical forms are treated as part of the provided compound definitions.
The invention also relates to treating a viral disease in a subject by administering a therapeutically effective dose of one or more compounds described in Formula (I), Formula (II), Formula (IV), and other formula-based definitions, including specified cyclohepta[b]indole/carbazole carboxylic acid compounds. The disclosed compounds are defined by substituent-variable constraints and include pharmaceutically acceptable salts, stereoisomers, and where stated, prodrugs and solvates, with use in prophylaxis or treatment contexts for viral disorders including common cold, SARS, and COVID-19.
Claims Coverage
The independent claims identified across the provided claim sets cover methods for treating viral disease by administering therapeutically effective doses of formula-defined compounds. The inventive subject matter is concentrated in four claim frameworks for Formula (I), Formula (II), Formula (IV), and specific cyclohepta[b]indole/carbazole carboxylic acid compounds, with the compound scope defined by substituent-variable constraints and included pharmaceutically acceptable salts or stereoisomers.
Administering Formula (I) compounds for treating viral disease
A method for treating a viral disease in a subject comprising administering a therapeutically effective dose of one or more compounds described in Formula (I), with defined variables for W, Z, n, R1, R2, R7, and related substituent groups, including pharmaceutically acceptable salts or stereoisomers thereof.
Administering Formula (II) compounds for treating viral disease
A method for treating a viral disease in a subject comprising administering a therapeutically effective dose of one or more compounds described in Formula (II), with defined variables for n, R1, R2, R7, R, and related substituent groups, including pharmaceutically acceptable salts thereof.
Administering Formula (IV) compounds for treating viral disease
A method for treating a viral disease in a subject comprising administering a therapeutically effective dose of one or more compounds described in Formula (IV), with defined variables for n, R1, R2, R3, and restricted group options for G, including pharmaceutically acceptable salts thereof.
Administering specified cyclohepta[b]indole/carbazole carboxylic acids for treating viral disease
A method for treating a viral disease in a subject comprising administering a therapeutically effective dose of one or more selected cyclohepta[b]indole/carbazole carboxylic acid compounds, including pharmaceutically acceptable salts or stereoisomers thereof.
Collectively, the independent claims focus on treating viral disease by administering therapeutically effective doses of formula-defined compounds or specified cyclohepta[b]indole/carbazole carboxylic acids, with the claim scope supported by variable substituent definitions and inclusion of pharmaceutically acceptable salts, stereoisomers, and where stated, prodrugs or solvates.
Stated Advantages
Provides isotopically labeled analogs for metabolic, reaction kinetic studies, and detection/imaging studies, including PET and SPECT.
Provides utility in drug/substrate tissue distribution assays and radioactive treatment.
Supports antiviral use cases involving viral replication inhibition and related therapeutic approaches, including combination therapy.
Treating viral diseases including common cold, SARS, and COVID-19 by administering therapeutically effective doses of FABP4-binding compounds.
Providing therapies that include aerosol formulation and combination with an additional antiviral agent.
Allowing stereochemical forms, including pure optical isomers.
Documented Applications
Metabolic studies and reaction kinetic studies using isotopically labeled analogs.
Detection/imaging studies using isotopically labeled analogs, including PET and SPECT.
Drug/substrate tissue distribution assays and radioactive treatment using isotopically labeled analogs.
Antiviral treatment and/or prophylaxis of viral disease in a subject by administering formula-defined compounds.
Antiviral testing against human coronavirus OC43 using differentiated 3T3-L1 adipocytes and a TCID50 assay, with compound classification by fold reduction in viral titers.
Antiviral treatment of coronavirus infections including SARS, SARS-CoV, SARS-CoV-2, and MERS-CoV.
Treatment or prophylaxis of acute respiratory viral infections including common cold, SARS, and COVID-19.
Therapy in the form of a pharmaceutical composition, including aerosol formulation.
Combination therapy with an additional antiviral agent.
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