1-aminosulfonyl-2-carboxypyrrole derivatives as metallo-beta-lactamase inhibitors
Inventors
Wilkinson, Andrew • Cooper, Ian • Orr, David • FINLAYSON, JONATHAN • BUNT, ADAM • APPELQVIST, PIA • Wallberg, Hans • WÅNGSELL, FREDRIK • Kirkham, James
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Assignees
MemberInfex TherapeuticsInfex TherapeuticsInfex Therapeutics is a UK-based specialist engaged in the acquisition, development, and licensing of drugs targeting pandemic and critical-priority infectious diseases, including both bacterial and viral threats. The company has a focus on combating antimicrobial resistance (AMR) by progressing new therapies for life-threatening infections into clinical trials. Infex Therapeutics works collaboratively with global partners, leveraging a robust R&D infrastructure at Alderley Park, and is involved in industry partnerships, public-private initiatives, and clinical-stage development.
Infex Therapeutics is a UK-based specialist engaged in the acquisition, development, and licensing of drugs targeting pandemic and critical-priority infectious diseases, including both bacterial and viral threats. The company has a focus on combating antimicrobial resistance (AMR) by progressing new therapies for life-threatening infections into clinical trials. Infex Therapeutics works collaboratively with global partners, leveraging a robust R&D infrastructure at Alderley Park, and is involved in industry partnerships, public-private initiatives, and clinical-stage development.
Publication Number
US-12544359-B2
Publication Date
2026-02-10
Expiration Date
Abstract
This invention relates to compounds of formula (I) and methods of treatment using the compounds. The compounds of the invention can be used in combination with antibacterial agents to treat bacterial infections. More specifically, the compounds of formula (I) can be used in combination with a class of antibacterial agents known as carbapenems. The novel compounds of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.
Core Innovation
The invention relates to compounds of formula (I) and pharmaceutically acceptable salts, hydrates, or stereoisomers thereof. The compounds are defined by a core in which one of X and Y is N and the other is C, together with an optional linker group L selected from a bond or (CH2)a-Q-(CH2)b, where Q is selected from O, NH, SO2, C≡C, and C-C, or Q is absent.
The formula (I) compounds further define R1 as a 6 membered monocyclic aromatic, carbocyclic, heteroaromatic, or heterocyclic ring substituted by one R3 group, with optional substitution by 0 or 1 group selected from halo, C1-6 alkyl, and C1-6 haloalkyl. R2 is C(O)OH or C(O)OM, where M is a group 1 cation, and R3 is selected from defined amide, cyano, carboxylic, carboxamide, sulfonamide, sulfone ester, sulfonyl, sulfonate, and related structural motifs with further constraints on R4, R5, R6, R7, R8, R9, and the integer indices a, b, d, f, g, m, and n.
The compounds of formula (I) are stated to be particularly soluble versus certain prior art and to have fewer off-target interactions. The disclosure also states that the compounds function as metallo-β-lactamase inhibitor compounds and are positioned as synergists with carbapenems such as meropenem and imipenem.
Claims Coverage
The claim coverage centers on one independent compound claim directed to formula (I) and related pharmaceutically acceptable salt, hydrate, or stereoisomer forms, with multiple defining variables across X/Y, L, R1, R2, and R3. Additional claim coverage includes pharmaceutical compositions with pharmaceutically acceptable excipients, carbapenem antibacterial agents, and use for bacterial infections.
Formula (I) compound with constrained X/Y assignment
A compound of formula (I) or a pharmaceutically acceptable salt, hydrate, or stereoisomer thereof, wherein one of X and Y is N and the other is C.
Optional linker L defined by bond or alkylene-Q patterns
L is selected from a bond and (CH2)a-Q-(CH2)b, where Q is selected from O, NH, SO2, C≡C, and C-C, or Q is absent.
R1 ring substituted by one R3 group
R1 is a 6 membered monocyclic aromatic, carbocyclic, heteroaromatic, or heterocyclic ring substituted by one R3 group, and optionally by halo, C1-6 alkyl, or C1-6 haloalkyl.
R2 acid or group 1 cation carboxylate
R2 is C(O)OH or C(O)OM, wherein M is a group 1 cation.
Defined R3 substituent motifs with variable constraints
R3 is selected from defined amide, cyano, carboxylic acid, carboxamide, sulfonamide, sulfone ester, sulfonyl, sulfonate, and related motifs, with constraints on R4 through R9 and the indices a, b, d, f, g, m, and n.
Pharmaceutical composition with excipients
A pharmaceutical composition comprising a compound of formula (I) and one or more pharmaceutically acceptable excipients.
Carbapenem antibacterial agent in the composition
A pharmaceutical composition in which the antibacterial agent is a carbapenem, including meropenem, faropenem, imipenem, ertapenem, doripenem, panipenem/betamipron, biapenem, razupenem, tebipenem, lenapenem, and tomopenem.
Bacterial infection use
Use for bacterial infections caused by specified Gram-positive or Gram-negative bacteria, either aerobic or anaerobic.
The claim coverage is anchored by formula (I) compounds defined by the X/Y N/C core assignment, an optional L linker with defined Q options, and the R1, R2, and R3 substituent framework under additional variable constraints. The scope also extends to pharmaceutical compositions with excipients, carbapenem antibacterial agents, and use for bacterial infections characterized by Gram class and aerobic or anaerobic status.
Stated Advantages
Certain exemplified formula (I) compounds are more soluble than certain prior-art compounds.
Certain exemplified formula (I) compounds have fewer off-target interactions.
Restoring or prolonging carbapenem activity against Gram-negative resistant pathogens.
Enhances β-lactam antibacterial efficacy by inhibiting metallo-β-lactamase activity.
Documented Applications
A method for prevention or treatment of bacterial infections caused by specified Gram-positive or Gram-negative bacteria, either aerobic or anaerobic.
Pharmaceutical composition use context with a formula (I) compound and pharmaceutically acceptable excipients.
Synergistic metallo-β-lactamase inhibitor use with carbapenems such as meropenem and imipenem to address carbapenem resistance associated with metallo-β-lactamases.
Use against Gram-negative resistant pathogens, including ESBL-producing Enterobacteriaceae and ESKAPE pathogens.
Prevention and treatment of infections, including Gram-positive and Gram-negative, and aerobic and anaerobic infections, by administering a compound of Formula (I) as a metallo-β-lactamase inhibitor.
Combination therapy with β-lactam antibacterials, including meropenem, administered in single or separate dosage forms.
In vitro and in vivo use for inhibiting metallo-β-lactamase activity and for prevention or treatment of infections.
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