Heterocyclic compounds and their use in preventing or treating bacterial infections
Inventors
BRIAS, Julie • Chasset, Sophie • Chevreuil, Francis • Lecointe, Nicolas • Ledoussal, Benôit • Le Strat, Frédéric • VOMSCHEID, Sophie • Richard, Sébastien • Faivre, Fabien • Barbion, Julien • Caravano, Audrey • Le Fralliec, Géraldine • Simon, Christophe
Assignees
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Publication Number
US-10501481-B2
Publication Date
2019-12-10
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 of formula (I) in which W is a non-aromatic, unsaturated 5- or 6-member heterocycle comprising at least one N—R2 group and an (X)n group. X is independently selected from C(O), O, N, N(R2), S, S(O), and S(O)2, and the substituent framework includes variable groups R1, R2, R3, Q1 to Q6, Q3 to Q4, and optionally T, T1, T2, L, and integer parameters m, n, p, q, v, and w.
The compounds include pharmaceutically acceptable salts, zwitterions, racemates, diastereoisomers, enantiomers, geometric isomers, and tautomers. The structural scope further specifies permitted oxidation and quaternization variants, including carbon atoms forming C(O), sulfur atoms forming S(O) or S(O)2, and nitrogen atoms in a heterocycle or a tertiary amino group being further quaternized by a methyl group.
The invention also relates to pharmaceutical composition and kit formulations for antibacterial use of compounds of formula (I)/(A)/(B)/(I*)/(A*)/(B*), with pharmaceutically acceptable excipients and compatible antibacterial agent families including beta-lactams and ceftazidime. The disclosed compounds are described as antibacterial agents and beta-lactamase inhibitors for preventing or treating bacterial infections, including gram-positive and gram-negative bacteria and beta-lactamase-producing bacteria.
Claims Coverage
The consolidated claim coverage centers on formula (I) and its structural constraints, with the main inventive features being the heterocycle W, the permitted X set, the defined R1, R2, and R3 substituent classes, the Q and T substituent frameworks, and the stated oxidation, quaternization, pharmaceutically acceptable variant, composition, and treatment provisions.
Heterocyclic compound of formula (I) with W and X definition
A compound of formula (I) in which W is a non-aromatic, unsaturated 5- or 6-member heterocycle comprising at least one N—R2 group and an (X)n group, and X is selected from C(O), O, N, N(R2), S, S(O), and S(O)2.
Defined substituent framework for R1, R2, R3, and Q groups
R1 is a carbon-linked 4-, 5-, or 6-member heterocycle comprising at least one nitrogen atom and optionally substituted by one or more T1. R2, R3, Q1 to Q6, Q3 to Q4, T, T1, T2, L, and the parameters m, n, p, q, v, and w are defined by enumerated structural alternatives.
Oxidation and methyl quaternization allowances
Carbon atoms can be oxidized to C(O), sulfur atoms can be oxidized to S(O) or S(O)2, and nitrogen atoms in a heterocycle or a tertiary amino group can be further quaternized by a methyl group.
Pharmaceutical composition with excipient and antibacterial co-ingredients
A pharmaceutical composition comprising the compound together with a pharmaceutically acceptable excipient, and compatible antibacterial agent families including beta-lactams, with ceftazidime explicitly mentioned.
Treatment of bacterial infections
Use directed to preventing or treating bacterial infections, including infections caused by beta-lactamase-producing bacteria and gram-negative bacteria.
The claim coverage centers on a single formula (I) scaffold with tightly defined heterocycle and substituent classes, plus explicit oxidation, quaternization, salt, stereochemical, composition, and treatment language.
Stated Advantages
Antibacterial properties.
Beta-lactamase inhibitor activity.
Prevention or treatment of bacterial infections.
Overcoming evolving bacterial antibiotic resistance.
Optional combinations with other antibacterial and/or beta-lactam compounds.
Documented Applications
Preventing or treating bacterial infections, including gram-positive and gram-negative bacteria and beta-lactamase-producing bacteria.
Pharmaceutical compositions and kits comprising the compound together with pharmaceutically acceptable excipients.
Pharmaceutical compositions including beta-lactams and ceftazidime.
Treatment of urinary tract infection (UTI), pyelonephritis, and respiratory tract infection.
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