Antimicrobial compounds and methods of making and using the same
Inventors
Bhattacharjee, Ashoke • Duffy, Erin M. • Kanyo, Zoltan F. • Chowdhury, Somenath • Thakur, Vinay • Lau, Wan
Assignees
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Publication Number
US-10947237-B2
Publication Date
2021-03-16
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.
Core Innovation
The invention relates to compounds of Formula (A), including tautomers thereof and pharmaceutically acceptable salts. The compounds are characterized by a defined structural scaffold in which a bond position is selected as either a single bond or a double bond, with variable groups X and Z and W selected from specified heteroatom-containing substituents.
The Formula (A) compounds further define multiple variable substituents R1 through R13, with allowed values for R1 through R6 and optional substitution patterns for alkyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups. The definitions include ring-forming relationships in which R1 and R2, and R5 and R6 together with the Z atom, can form cycloalkyl or heterocycloalkyl ring systems.
The scope is further controlled by ring and heteroatom constraints for R5 and R6, including conditions that at least one of R5 and R6 is not H and that selected combinations of R5 and R6 with the Z atom form a (C5-C6) cycloalkyl or a 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms. The document also provides multiple conditional restrictions and explicit exclusions using provided that clauses to delimit the claimed chemical space.
Claims Coverage
The claim coverage centers on one independent claim defining a compound of Formula (A), including tautomer and pharmaceutically acceptable salt coverage, with extensive structural variability using X, Z, W, and substituents R1 through R13, together with multiple conditional restrictions and exclusion conditions.
Compounds of Formula (A) as tautomers and salts
A compound of Formula (A), or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer, with defined structural variables including a single or double bond and variable substituent positions.
Defined heteroatom link and variable substituent patterns
X is selected from specified amino- and heteroatom-containing groups; Z is selected from O, CH2, NR11, or S(O)p; and W is selected from N(R5) or C(R5)(R5′).
Substituent sets for R1 through R6 and conditional non-H constraints
R1 through R6 are defined by enumerated chemical possibilities, including optional substitution patterns for alkyl, alkenyl, cycloalkyl, heterocycloalkyl, and heteroaryl groups, with the additional requirement that at least one of R5 and R6 is not H.
Ring-forming rules linking substituents and Z
R1 and R2 may form a (C3-C7)cycloalkyl or heterocycloalkyl ring, and R5 and R6 together with the Z atom may form a (C5-C6)cycloalkyl or 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms; when W is N(R5), R6 and W together with the Z atom may form a 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms.
Provided-that exclusion conditions
The claim includes explicit provided-that restrictions that limit specific combinations of Z, X, W, R1 through R4, R5, R6, and R13/R13′, including additional exclusions for selected variable choices.
Overall, the claim coverage centers on a Formula (A) compound genus with extensive variable-group definitions, ring-forming rules, tautomer and salt coverage, and explicit conditional exclusions that limit specific substituent combinations.
Stated Advantages
Antimicrobial ribosome-targeting compounds.
Rationales based on structure-based drug design using high-resolution ribosome X-ray structures.
Documented Applications
Treating microbial infection in humans or animals.
Preventing microbial infection in humans or animals.
Reducing risk of microbial infection.
Delaying onset of microbial infection.
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