Anti-infective compounds
Inventors
Kim, Jaeseung • Kang, Sunhee • KANG, Juhee • LEE, Sumi • Seo, Jeong Jea • SEO, Mooyoung
Assignees
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Publication Number
US-11279714-B2
Publication Date
2022-03-22
Expiration Date
Abstract
The present invention relates to small molecule compounds having the general formula (I): wherein A is a moiety selected from the group consisting of formulae (A) to (K) and their use in the treatment of bacterial infections, in particular Tuberculosis.
Core Innovation
The document describes compounds for treating bacterial infections, especially tuberculosis, built around general formula I, general formula III, formulae II-IV, and formulae Ia and Ib, as well as compounds defined by multiple alternative depicted formulae and structures in accompanying structure sets. The scaffold is characterized by fused sulfur- and nitrogen-containing heteroaromatic cores with amide-, urea-, or carboxamide-like linkages to substituted aromatic or heteroaromatic fragments.
The disclosed structures vary by extensive substituent and heteroatom selections, including n1, n2, m, o, p, q, X1, X2, Y, V, W, R1 through R9, and Z, together with fused heteroaryl groups and cyclic amine substituents such as morpholine-like, piperidine-like, and piperazine-like groups. The compounds also include halogens, hydroxy, methoxy or alkoxy, methyl, cyano, nitro, amino, sulfonyl or sulfonic acid features, and pharmaceutically acceptable salts.
The document provides characterization data for multiple specific examples, including appearance, melting point, 1H NMR, and LCMS electrospray m/z values, with associated CDX/MOL or embedded image references. It also documents biological evaluation in infected macrophages, intracellular growth inhibition, phenotypic high-content screening, and resazurin microtitre assay contexts, together with activity categories and MIC-related activity levels.
Claims Coverage
The independent claims cover compound families defined by general formula I and general formula III, together with compounds selected from one of multiple listed formulae or structures in accompanying structure sets. Across the independent claims, the coverage emphasizes highly variable core scaffolds with extensive substituent, heteroatom, linker, and ring-connection options, and includes pharmaceutically acceptable salts.
General formula I compound scaffold
A compound having the general formula I with n1 and n2 independently 0-3, m=1, and A as a moiety selected from a group defined by variable fused heteroaryl groups; R1 and R2 are selected from defined substituent sets, and structural variables include o, p, q, X1, X2, Y, V, W, R3 through R7, and Z, with pharmaceutically acceptable salts.
General formula III compound scaffold
A compound having the general formula III with n 0-3, m=1, o 0-3, q 0-1, X2 as CRbRc/O/S/NR6, Y as C2-C6 alkylene/S/NR6, W as C1-C6 alkylene, and R5, R6, R8, and R9 selected from defined substituent groups, with Z selected from defined substituent and formula Ib options and with pharmaceutically acceptable salts.
Selected structure-set compound
A compound having one of the formulae selected from multiple numbered structures provided in an accompanying structure set, including compounds defined by a selected formula or depicted structure from the listed set.
The independent claim coverage centers on chemical compounds defined by general formula scaffolds and by selection from alternative depicted formulae or structures, with claim scope driven by extensive substituent variability, heteroatom and linker definitions, ring-connection options, and inclusion of pharmaceutically acceptable salts.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating bacterial infections, especially tuberculosis.
Inhibiting intracellular growth of M. tuberculosis in infected macrophages.
Use in phenotypic high-content screening and resazurin microtitre assay contexts to assess activity in relevant cellular systems.
In vitro growth fluorescence and intracellular growth assay evaluation of compounds with activity scoring categories.
Antibacterial activity against multidrug-resistant tuberculosis isolates.
Oral lozenges, pastilles, and mouthwashes are described as administration routes for the compounds.
Intranasal delivery is described via intranasal solutions, sprays, and aerosols.
Dry-powder inhalation is described for the compounds.
Evaluation is described for anti–Mycobacterium tuberculosis activity using intracellular and in vitro mycobacteria quantification and MIC/MIC50 determination.
Pharmaceutical unit-dose and sustained release options are described as formulation contexts.
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