Antiviral compounds and methods of use thereof

Inventors

GUENTHER, Richard H. • Szewczyk, Jerzy R.

Assignees

Trana Discovery Inc

Abstract

The present invention is drawn to a pharmaceutical composition comprising the following compound:The compound and other azacycle derivatives can be used in method of treatments for retroviral infections, such as HIV.

Core Innovation

The invention relates to antiviral compounds defined by structural formulas and their use as retroviral propagation inhibitors. The disclosed compounds include azacycle-containing cores, substituted-aryl and heteroaryl variants, and highly conjugated molecules presented in defined chemical formulas and associated stereochemical forms, including racemates and enantiomerically enriched forms.

The disclosure describes inhibition of retroviral propagation through reverse transcription-related effects, primer recruitment, tRNA recruitment and binding, translation, and final packaging and assembly of new virions. It links inhibitor activity to human tRNA-Lys3 and tRNA anticodon stem loop fragment interactions, including host cell tRNA binding to a target nucleic acid, and includes inhibitor identification and screening assays using tRNA fragments and target nucleic acids.

The scope includes nitrogen- and sulfur-containing conjugated scaffolds and substitution patterns, ester-to-amide stability modifications and related replacements, optional solubilizing groups using morpholine and piperidine-containing substituents, and aryl-to-heteroaryl substitution patterns. The disclosure also covers salts and free bases formulated with pharmaceutically acceptable carriers, with representative examples provided for a broad set of compounds, and excludes Formulas H and I.

The disclosed compounds are provided as pharmaceutical compositions comprising the compound in combination with a pharmaceutically acceptable carrier, formulated as a pill, tablet, capsule, or caplet. The disclosure also frames use in treating HIV retroviral infection by administering a compound of the defined formulas to a patient in need of treatment, with structural constraints including a 4-8 membered ring azacycle and an integer j from 0-3.

Claims Coverage

The provided claim set identifies independent claim themes directed to a pharmaceutical composition and a method of treating HIV, with further refinements related to retroviral inhibition and combination therapy. Across the claims, the core coverage includes formulation of a compound of specified formulas with a pharmaceutically acceptable carrier in standard solid dosage forms and administration of a structurally defined compound to a patient with HIV.

Overall, the claims cover pharmaceutical compositions containing compounds of defined formulas with pharmaceutically acceptable carriers and methods for treating HIV using structurally defined compounds. The inventive features also include claim refinements that identify which HIV strain or variant is treated, define the inhibitor’s retroviral activity, and optionally specify a combination regimen by co-administering a second antiretroviral agent from a listed group.

Stated Advantages

Documented Applications