Heterocyclic compounds and their use in preventing or treating bacterial infections
Inventors
BRIAS, Julie • Chasset, Sophie • Chevreuil, Francis • Lecointe, Nicolas • Ledoussal, Benoit • Le Strat, Frédéric • Barbion, Julien
Assignees
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Publication Number
US-10842779-B2
Publication Date
2020-11-24
Expiration Date
Abstract
The present invention relates to heterocyclic compounds, their process of preparation, pharmaceutical compositions comprising these compounds and use thereof, optionally in combination with other antibacterial agents and/or beta-lactam compounds, for the prevention or treatment of bacterial infections. The present invention also relates to the use of these compounds as β-lactamase inhibitors and/or as antibacterial agents.
Core Innovation
The invention relates to compounds defined by formula (I), including pharmaceutically acceptable salts, zwitterions, optical isomers, racemates, diastereoisomers, enantiomers, geometric isomers and tautomers. The compounds are characterized by an A-B linkage defined either as a CH=CH unit or as a ring W, and ring W is unsubstituted or substituted by one or more T and is selected from phenyl or specified aromatic heterocycles.
The formula (I) further includes substituent definitions for R1, R2 and R3. R1 represents oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, imidazoline, oxadiazole, thiadiazole, triazole, tetrazole, or substituted or unsubstituted derivatives thereof, and R2 is SO3H, CFHCO2H, or CF2CO2H. Optional oxidation and quaternization are included, in which carbon atoms can be oxidized to form a C=O group, sulphur atoms in a heterocycle can be oxidized to form S=O or S(O)2, and tertiary amino groups can be quaternized by a methyl group with a counter ion to maintain pharmaceutical acceptability.
The compound family is associated with preventing or treating bacterial infections and acting as β-lactamase inhibitors and antibacterial agents. The subject matter also includes pharmaceutical composition and kit frameworks, with pharmaceutically acceptable excipient or carrier and antibacterial co-agent or kit examples.
Claims Coverage
The provided material identifies one independent compound claim and dependent claim themes around pharmaceutical compositions, antibacterial co-ingredients, treatment, and kit-based administration. The claim coverage centers on the formula (I) compound family and includes five inventive features across the compound, composition, co-antibacterial, treatment, and kit themes.
Formula (I) compound with variable A-B linkage and substituents
A compound of formula (I) wherein A-B is either a CH=CH double bond or a ring W; ring W is a phenyl group or a 5-membered aromatic heterocycle comprising one to three heteroatom(s) selected from O, N, N(R3), S, S(O) or S(O)2, or a 6-membered aromatic heterocycle comprising 1, 2 or 3 nitrogen heteroatom(s); R1 represents oxazole, isoxazole, thiazole, isothiazole, pyrazole, imidazole, imidazoline, oxadiazole, thiadiazole, triazole, tetrazole, or substituted or unsubstituted derivatives thereof; R2 represents SO3H, CFHCO2H or CF2CO2H; and the optional salt, zwitterion, stereoisomeric and tautomeric forms are included.
Optional oxidation and quaternization enabling pharmaceutical acceptability
Carbon atoms within selected groups can be oxidized to form a C=O group, sulphur atoms in a heterocycle can be oxidized to form S=O or S(O)2, and tertiary amino groups can be quaternized by a methyl group with a counter ion to maintain pharmaceutical acceptability.
Pharmaceutical composition with formula (I) compound and pharmaceutically acceptable carrier
A pharmaceutical composition comprising at least one compound according to formula (I) together with an effective amount and a pharmaceutically acceptable carrier.
Pharmaceutical composition including an antibacterial co-ingredient
The pharmaceutical composition further includes one or more antibacterial compounds selected from aminoglycosides, β-lactams, glycylcyclines, tetracyclines, quinolones, fluoroquinolones, glycopeptides, lipopeptides, macrolides, ketolides, lincosamides, streptogramins, oxazolidinones, polymyxins, and mixtures thereof.
Treatment for β-lactamase-producing bacterial infections
A method of treating bacterial infections using the composition as claimed where the bacteria are Gram-positive or Gram-negative and the bacterial infections are caused by bacteria that produce one or more β-lactamase.
Kit-based administration using at least two pharmaceutical compositions
A method for treating bacterial infections by administering at least two pharmaceutical compositions from a kit to a person, simultaneously, separately, or sequentially.
The core inventive element is the formula (I) compound family defined by the A-B linkage and substitution using R1 and R2, including SO3H and carboxylic acid variants, with optional stereochemical, tautomeric, salt, and zwitterion forms. Dependent coverage extends to pharmaceutical compositions with a pharmaceutically acceptable carrier, addition of antibacterial co-compounds selected from enumerated antibiotic classes including β-lactam compounds, treatment of β-lactamase-producing Gram-positive or Gram-negative bacteria, and kit-based administration using at least two pharmaceutical compositions.
Stated Advantages
Provides compounds for preventing or treating bacterial infections.
Acts as β-lactamase inhibitors and antibacterial agents.
Overcomes antibiotic resistance.
Supports pharmaceutical composition and kit frameworks for treatment.
Documented Applications
Preventing or treating bacterial infections.
Overcoming antibiotic resistance.
Treatment of bacterial infections caused by bacteria producing one or more β-lactamase, including Gram-positive and Gram-negative bacteria.
Use in pharmaceutical composition and kit-based treatment methods administered simultaneously, separately, or sequentially with at least two pharmaceutical compositions.
Infection indications are explicitly illustrated, including UTI, pyelonephritis, CAP/HAP/VAP, and sepsis.
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