Heterocyclic compounds and their use in preventing or treating bacterial infections
Inventors
Barbion, Julien • Caravano, Audrey • Chasset, Sophie • Chevreuil, Francis • Le Strat, Frédéric • Simon, Christophe • BRIAS, Julie • LEBEL, Rémi
Assignees
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Publication Number
US-11865118-B2
Publication Date
2024-01-09
Expiration Date
Abstract
The present invention relates to compounds of formula (I) and their use for treating or preventing a bacterial infection or as an antibacterial agent and/or as a β-lactamase inhibitor.
Core Innovation
The invention relates to compounds of formula (I) and formula (I*), including racemate, enantiomer, diastereoisomer, geometric isomer and pharmaceutically acceptable salt thereof. The compounds are defined by extensive structural variable selections for groups including R1, R2, R3, Y1, Y2, Y3, Y4, Y5, X1, X2, X3, X4, A1, X6, X7, X8, and Z1 to Z4, together with allowance for oxidation of sulfur atoms within a heterocycle to form a S=O group or a S(O)2 group, and quaternization of a tertiary amino group.
The invention addresses the therapeutic control of bacteria and the treatment and/or prevention of infection using the compounds of formula (I)/(I*) and related embodiments. The subject matter identifies bacterial species including Escherichia species, Enterobacter species, Pseudomonas aeruginosa, and gram-positive bacteria such as Staphylococcus, Streptococcus, and Enterococcus.
The document further characterizes the invention in terms of pharmaceutical compositions and drug products containing the compounds together with pharmaceutically acceptable excipients, and describes combination therapy concepts in which the compounds of formula (I)/(I*) are administered with one or more antibacterial agents, preferably beta-lactams, including ceftazidime and other beta-lactam subclasses. Kit concepts are also described, including separate compositions for extemporaneous mixing and concepts for simultaneous, separated, and/or sequential administration.
Claims Coverage
The provided partial content includes two independent claims: a compound claim covering compounds of formula (I) with extensive structural definitions, and a method claim covering treatment of bacterial infections by administering those compounds to a person in need. Across these independent claims, the core inventive features are the chemical genus of formula (I) and its use for treating specified bacterial infections.
Compound of formula (I) with variable substituent definitions
A compound of formula (I) with defined selections for R1, n, R2/R3, Y1/Y2/Y3/Y4/Y5, X1/X2, X3/X4, A1, X6/X7/X8, and Z1-Z4, including allowance for sulfur oxidation to form a S=O group or a S(O)2 group and quaternization of a tertiary amino group by a methyl group, together with racemate, enantiomer, diastereoisomer, geometric isomer or a pharmaceutically acceptable salt thereof under the stated exceptions.
Treating bacterial infection by administering compound of formula (I)
A method for treating a bacterial infection caused by Escherichia species, Enterobacter species or P. aeruginosa by administering to a person in need thereof a compound of formula (I) defined by the same variable substituent definitions, including stereoisomer and pharmaceutically acceptable salt options and the same sulfur oxidation and amino quaternization allowances.
The independent claims cover a defined chemical genus of compounds of formula (I) with extensive substituent and structural correspondence constraints, including oxidation/quaternization and stereochemical/salt forms, and therapeutic use of those compounds to treat bacterial infections caused by specified bacterial species by administering the formula (I) compounds to a person in need.
Stated Advantages
Antibacterial properties.
β-lactamase inhibitor utility.
Documented Applications
Utility as antibacterial and β-lactamase inhibitors for compounds within formula (I).
Treatment of a bacterial infection caused by Escherichia species, Enterobacter species or P. aeruginosa by administration to a person in need thereof.
Biological MIC testing synergy context is explicitly reported for combinations of ceftazidime with compounds against Gram-negative isolates including E. coli, Enterobacter cloacae, Klebsiella pneumoniae, and P. aeruginosa, with MICs reported for compounds alone and combinations at fixed compound concentrations.
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