Antimicrobial compounds and methods of making and using the same
Inventors
Duffy, Erin M. • Bhattacharjee, Ashoke • Kanyo, Zoltan F. • Ippolito, Joseph A. • Marra, Andrea
Assignees
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Publication Number
US-12234238-B2
Publication Date
2025-02-25
Expiration Date
Abstract
The present disclosure relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals.In some embodiments, the present disclosure provides a compound of Formula (I):or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
Core Innovation
The invention relates to a compound of formula (AA), including a tautomer thereof and a pharmaceutically acceptable salt of the compound or tautomer. Formula (AA) is defined by structural variables J, X, Z, Q, R1 through R8, and additional R substituents, with optional substitution patterns, stereochemical specification, and ring-forming relationships.
The structural scope includes selections for heterocyclyl and phenyl rings, nested substituent definitions for variables such as Rx, Ra, Rb, Rc, and Rd, and conditional ring formation involving R1 through R3 with nitrogen atoms and a connecting carbon atom. It also includes ring motifs involving R5/R7 and R6/R7 together with allowed linker selection for Q.
The document further describes compounds as ribosome-binding compounds and states therapeutic context for preventing and treating microbial infection, including microbial infections caused by multidrug-resistant organisms and ESKAPE pathogens. It also refers to pharmaceutical compositions, examples, stereoisomer representations, and animal model evaluation contexts, while presenting representative structural embodiments and formula variants such as Formula IIA, IIB, III, IIIA, and IIIB.
Claims Coverage
The consolidated claim coverage centers on one independent claim defining compound formula (AA), including tautomer and pharmaceutically acceptable salt forms, with broad but structured selection rules for heterocycle or phenyl choice, substituent variables, and ring formation. The inventive features are the multi-parameter formula framework and the explicit connectivity constraints involving nitrogen-associated ring motifs and variable substituent combinations.
Multi-parameter compound of formula (AA) with tautomer and pharmaceutically acceptable salt
A compound of formula (AA), or a tautomer thereof, or a pharmaceutically acceptable salt of the compound or tautomer, defined by selections for J, X, Z, Q, R1 through R8, and additional R substituents.
Heterocycle and phenyl selection for J and X with optional substitution
J and X are selected from specified heterocyclyl ring and phenyl options, wherein each ring is optionally substituted with one or more Rx.
Conditional substitution and ring formation for Z using R1 through R3
R1, R2, and R3 are independently selected from H and C1-3 alkyl with explicit combination limits, or selected groups together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring.
Substituent scope for R5, R6, and R7 with ring-forming options
R5 is selected from H and C1-6 alkyl; R6 is selected from H, C1-6 alkyl, C2-6 alkenyl, and C3-6 cycloalkyl; R7 is selected from H and C1-6 alkyl; and R6/R7 or R5/R7 may together form a ring having one of the specified formulas, with optional ring-carbon substitution.
Linker selection for Q and terminal substituent constraints for R8 and R21
Q is selected from C1-2 alkylene or —C(O)—; R21 is selected from H or C1-6 alkyl optionally substituted with 1-3 halo; and R8 is selected from H and halogen.
Nested substituent definitions for Rx, Ra, Rb, Rc, and Rd
Each Rx, Ra, Rb, Rc, and Rd is defined by listed substituent ranges, including halogen, alkyl, haloalkyl, ORc, N(Rc)2, carbonyl-linked groups, cycloalkyl, aryl, hydroxyl, amino, nitro, and alkylamino patterns, with optional ring closure for adjacent Rx groups.
Overall, the claim coverage is driven by the generic structural definition of formula (AA) together with explicit substitution, tautomer, salt, and ring-forming constraints. The key inventive features are the controlled heterocycle or phenyl selection, the Z-region and R5/R6/R7 connectivity rules, the Q linker choice, and the nested substituent definitions.
Stated Advantages
Therapeutic use against microbial infections, including ESKAPE pathogens and multidrug-resistant organisms.
Use against biodefense/biological-weapon microorganisms.
Binding bacterial ribosomes and inhibition of bacterial ribosome function.
Prevents and treats microbial infections.
Provides in vitro MIC/MIC90 ranges and reported resistance profile and safety model highlights.
Documented Applications
Therapeutic use against microbial infections including ESKAPE pathogens and multidrug-resistant organisms.
Use against biodefense/biological-weapon microorganisms.
Treatment of bacterial infection.
Pharmaceutical compositions for preventing and treating microbial infection using the disclosed compound and related tautomers and pharmaceutically acceptable salts.
Method of treating microbial infection.
Method of preventing microbial infection.
Method of reducing risk of microbial infection.
Method of delaying onset of microbial infection.
Animal model evaluation contexts referenced in the disclosure, including neutropenic thigh model, ascending kidney model, lung model, and peritonitis model.
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