Antimicrobial compounds, compositions, and uses thereof
Inventors
Kates, Steven A. • Sleet, Randolph B. • Parkinson, Steven
Assignees
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Publication Number
US-11795192-B2
Publication Date
2023-10-24
Expiration Date
Abstract
Antimicrobial compounds and compositions of Formulas (V), (VI), (VII), (VIII), and (IX), and methods of use are disclosed.
Core Innovation
The disclosure concerns compounds having specified formulas, or pharmaceutically acceptable salts thereof, shown in multiple chemical structure depictions and associated structure files. The compounds share fused bicyclic or heteroaromatic scaffolds with ring nitrogens and amino substituents, including exocyclic primary amine groups, and in some examples additional carbonyl, oxygen, sulfur, or heteroatom-containing features. Variable substituent patterns are represented by wavy attachment points and side-chain fragments such as alkyl, cycloalkyl, hydrophobic, hydroxyl-terminated, and branched substituent groups.
The compound examples include fused bicyclic heteroaromatic systems described with benzene, benzimidazole-like, quinazoline-like, indazole/pyridine-like, triazine-like, benzothiazine-thione/benzoxazinone-like, thiophene-fused, indole, indazole, phenoxazine, phenothiazine, piperidine, piperazine, morpholine, oxazine, thiazine, aziridine, azetidine, β-lactam, pyrrolidine, and related heterocyclic frameworks. The disclosed series presents different substituent positions and scaffold variants while maintaining the same general formula-defined compound class, including guanidino substituted ring systems and phosphonate/phosphate-containing compounds in one portion of the record.
The claim context links these formula-defined compounds to therapeutic use in treating infections and tissue conditions. The provided material identifies treatment targets including bladder and/or urinary tract infection, lung infection, pneumonia, ventilator-acquired pneumonia, burn wound infection, otitis externa, bacterial vaginosis, impetigo, oral mucositis, lower extremity infection, and diabetic foot ulcer infection, with additional limitations for lung infection based on pulmonary-condition origin and enumerated pulmonary conditions. One portion of the record also reports comparative physico-chemical and antibacterial results, including improved antibacterial activity, pH-dependent improvements in MIC, bacterial cytological profiling effects, and in vivo efficacy in UTI and Helicobacter pylori models.
Claims Coverage
The consolidated claim coverage centers on compounds defined by a specified formula and pharmaceutically acceptable salts, with dependent claim families extending to treatment methods and pharmaceutical compositions. The merged inventive features repeatedly cover the compound formula itself, treatment of bladder and/or urinary tract infection, lung infection limitations tied to pulmonary conditions, ventilator-acquired pneumonia, a pharmaceutical composition with carriers, excipients, or diluents, and additional listed infections and tissue conditions. In one record portion, the claims also cover treatment of burn wound infection, otitis externa, bacterial vaginosis, impetigo, oral mucositis, lower extremity infection, and diabetic foot ulcer infection.
Formula-defined compound and pharmaceutically acceptable salt
A compound having the formula, or a pharmaceutically acceptable salt thereof.
Treatment of bladder and/or urinary tract infection by administering an effective amount
Administering an effective amount of the compound of the formula, or a pharmaceutically acceptable salt thereof, to a patient in need to treat a bladder and/or urinary tract infection.
Lung infection originating from a pulmonary condition
A method for treating a lung infection in which the lung infection originates from a pulmonary condition, with the pulmonary condition selected from a specified group of named pulmonary conditions, alone or in combination.
Ventilator-acquired pneumonia treatment
A method applied to cases of ventilator-acquired pneumonia.
Pharmaceutical composition with pharmaceutically acceptable carriers, excipients, or diluents
A pharmaceutical composition including the compound of the formula, or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable carriers, excipients, or diluents.
Treatment of additional listed infections and tissue conditions
A method of treating additional explicitly listed infections and tissue conditions, including pneumonia, burn wound infection, otitis externa, bacterial vaginosis, impetigo, oral mucositis, lower extremity infection, and diabetic foot ulcer infection.
Overall, the claim coverage is anchored by compounds defined by a formula and pharmaceutically acceptable salts. The dependent claims consistently refine use by administering an effective amount for specified infections and tissue conditions, especially bladder and/or urinary tract infection and lung infection with pulmonary-condition limitations, including ventilator-acquired pneumonia, and by a pharmaceutical composition embodiment containing pharmaceutically acceptable carriers, excipients, or diluents.
Stated Advantages
Improved antibacterial activity, including faster killing and viability reduction.
pH-dependent improvements in MIC.
Bacterial cytological profiling effects.
In vivo efficacy in UTI and Helicobacter pylori models.
Free amino/guanidino groups provide unexpectedly higher potency at a pH above about 3, and the compounds show improved suitability for topical, inhalation, and intravesical administration and for slow-growth bacteria.
Documented Applications
Treating bladder and/or urinary tract infection by administering an effective amount of the claimed compound or a pharmaceutically acceptable salt thereof to a patient in need.
Treating lung infection where the lung infection originates from a pulmonary condition selected from a specified group of named pulmonary conditions.
Treating ventilator-acquired pneumonia.
Treating burn wound infection, otitis externa, bacterial vaginosis, impetigo, oral mucositis, lower extremity infection, diabetic foot ulcer infection, and pneumonia.
Providing a pharmaceutical composition comprising the claimed compound or a pharmaceutically acceptable salt thereof with pharmaceutically acceptable carriers, excipients, or diluents.
In vivo efficacy in mouse/rath UTI models and Helicobacter pylori models.
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