Salicyl-adenosinemonosulfamate analogs and uses thereof
Inventors
Tan, Derek Shieh • Standke, Lisa Charlotte • Quadri, Luis Edmundo Nereo • Bythrow, Glennon Valere • Bishai, William Ramses • Lun, Shichun
Assignees
Research Foundation of City University of New York • Johns Hopkins University • Memorial Sloan Kettering Cancer Center
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Publication Number
US-12435088-B2
Publication Date
2025-10-07
Expiration Date
Abstract
Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts or tautomers thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment and/or prevention of an infectious disease (e.g., bacterial infection (e.g., Mycobacterium infection (e.g., tuberculosis)). (I)
Core Innovation
The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts, stereoisomers, tautomers, or prodrug forms thereof, with extensive structural variability governed by substituent variables R1, R2, R3, R4, R5, R7, Re, R8, R9, R10, R11, R12, X1, q, and n. The scaffold includes allowed alkyl, heteroalkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, acyl, and multiple heteroatom-containing substituent options, together with ring-joining rules for selected substituent pairs and defined linkage options for X1.
The compounds further permit optional substituent patterns such as halogen, nitro, cyano, hydroxy, amino, sulfonyl, sulfonamide, sulfonate, thio, oxy, and protecting-group-related variations, as explicitly stated in the inputs. The integer q is limited to 1, 2, or 3, and n is limited to 0, 1, 2, 3, 4, or 5. Some provided items also describe variable Z and R6 moieties, including OR8 groups, halo-containing substituents, sulfonyl-linked alkyl chains, and cyclic ether fragments.
The provided description content additionally includes pharmaceutical compositions containing a compound of Formula (I) with pharmaceutically acceptable excipients and optional additional therapeutic agents, including antibiotics. The documents describe therapeutic and prophylactic use in infectious diseases, including bacterial infections such as Mycobacterium tuberculosis/tuberculosis, and identify biological pathway targets including siderophore biosynthesis, PQS biosynthesis, virulence factor biosynthesis, and biofilm formation.
Claims Coverage
The consolidated claim coverage centers on a broad Formula (I) compound claim with extensive substituent and linkage variability, plus dependent use and refinement claims expressly stated in the inputs. Across the items, the inventive features include compound claims, infectious disease treatment or prevention, and inhibition of siderophore biosynthesis during infection.
Compounds of formula (i) with broad substituent variability
A compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof, with broadly defined substituents including R1, R2, R3, R4, R5, R7, Re, R8, R9, R10, R11, R12, and ring-joining rules.
Linkage and ring-formation constraints via x1, q, and n
X1 is a bond, O—, (C(Rd)2)q—, or —NRe—, with q being 1, 2, or 3 and n being 0, 1, 2, 3, 4, or 5; selected substituent pairs may be joined to form optionally substituted carbocyclic, heterocyclic, aryl, or heteroaryl rings.
Infection treatment or prevention by administration
A method for treating or preventing an infectious disease comprising administering an effective amount of a compound of Formula (I) to a subject in need.
Inhibition of siderophore biosynthesis during infection
A method for inhibiting siderophore biosynthesis during an infection in a subject comprising administering a compound of Formula (I).
Specific refinement that re is hydrogen
Each occurrence of Re is hydrogen, as expressly stated in a dependent refinement in the provided inputs.
Specific refinement of r1 substituent set
R1 is selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, or trifluoromethyl, as expressly stated in the provided inputs.
The claims are anchored by the broad Formula (I) scaffold with extensive substituent, linkage, and ring-formation rules, and they extend to expressly stated infectious disease treatment or prevention and siderophore biosynthesis inhibition methods. The inputs also include narrower refinements, including Re set to hydrogen and a defined R1 substituent set.
Stated Advantages
Therapeutically effective and prophylactically effective inhibition of siderophore biosynthesis and related biosynthetic pathways for infectious disease contexts.
Inhibition of PQS biosynthesis and virulence factor biosynthesis, including pyocyanin and yersiniabactin.
Use in treating or preventing infectious disease, including bacterial infections such as Mycobacterium tuberculosis/tuberculosis.
Documented Applications
Treating or preventing infectious disease by administering a compound of Formula (I) to a subject in need.
Inhibiting siderophore biosynthesis during an infection in a subject by administering a compound of Formula (I).
Applications explicitly described for bacterial infections including Mycobacterium tuberculosis/tuberculosis.
Infection contexts including MBT biosynthesis, PQS biosynthesis, virulence factor biosynthesis, and biofilm formation.
Pharmaceutical compositions containing a compound of Formula (I) with pharmaceutically acceptable excipients and optional additional therapeutic agents, including antibiotics.
Kit concepts with instructions.
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