Oxazolidinone antibiotic compounds and process of preparation
Inventors
Peer Mohamed, Shahul Hameed • Bharatham, Nagakumar • KATAGIHALLIMATH, NAINESH • SHARMA, SREEVALLI • NANDISHAIAH, RADHA • Ramachandran, Vasanthi
Assignees
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Publication Number
US-11590142-B2
Publication Date
2023-02-28
Expiration Date
Abstract
Compounds of Formula I, its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivative thereof and pharmaceutical compositions containing them as the active ingredient which can be used as medicaments are provided. The aforementioned substances can also be used in the manufacture of medicaments for treatment, prevention, or suppression of diseases, and conditions mediated by microbes. Methods for the synthesis and characterization of the aforementioned substances are also provided.
Core Innovation
The invention relates to a compound of Formula I, including its stereoisomers and pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms, and pharmaceutically active derivatives. The structural definition uses variable selections for R1-R8, X1-X2, Y1-Y2, Z1, n1, and n2, with substituents and ring features chosen from specified groups. The chemical scope defines a large family of Formula I analogs within defined options for substituent identity and heterocyclic ring features.
The compounds of Formula I are described as medicaments for inhibiting and/or killing microorganisms, including bacteria, virus, fungi, and protozoa, with particular emphasis on Gram-positive pathogens and Gram-negative pathogens. The invention is further supported by antibacterial and enzyme inhibition activity, including inhibition of E. coli DNA gyrase and E. coli Topo IV, together with potency across Gram-positive and Gram-negative strains. Minimum Inhibitory Concentration data and enzyme inhibition assays are included, and a specific clinical-strain result is reported for Compound 7 as MIC50/90.
The disclosure also includes pharmaceutical compositions that include a compound of Formula I in combination with a pharmaceutically acceptable carrier, and optionally in combination with at least one antibiotic. The provided content describes synthesis and characterization for multiple specific Formula I analogs, including LC-MS, 1H NMR, and HPLC purity reporting for Compounds 4-14. Preparation approaches associated with specific intermediates are described at a high level.
Claims Coverage
The claim coverage centers on a Formula I compound family defined by broad substituent and variable selections, including stereoisomers and pharmaceutically acceptable forms, and additional claim categories cover a method and a pharmaceutical composition. The inventive scope therefore includes the compound definition of Formula I and independent use and composition concepts grounded in treating or inhibiting microorganisms and forming pharmaceutical compositions.
Formula I compound family in pharmaceutically acceptable forms
A compound of Formula I or its stereoisomers, including pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms and pharmaceutically active derivatives, wherein substituent and ring-variable selections are defined for R1-R8, X1-X2, Y1-Y2, Z1, n1 and n2 from specified chemical-group options.
Method to kill or inhibit microorganism growth by administering an effective amount
A method to kill or inhibit growth of a selected microorganism in a subject by administering an effective amount of the compound described in the Formula I claim, wherein the microorganism includes bacteria, virus, fungi, or protozoa.
Pharmaceutical composition with carrier combined with at least one antibiotic
A pharmaceutical composition comprising a compound of Formula I together with a pharmaceutically acceptable carrier, wherein the composition is combined with at least one antibiotic.
Overall, the claim coverage establishes broad protection for Formula I analog structures in pharmaceutically acceptable forms and extends to administering the compound to kill or inhibit microorganism growth and to pharmaceutical compositions that include a pharmaceutically acceptable carrier combined with at least one antibiotic.
Stated Advantages
Inhibits and/or kills microorganisms, including bacteria, virus, fungi, and protozoa.
Provides medicaments for Gram-positive and Gram-negative pathogens.
Provides antibacterial activity, as supported by MIC data across Gram-positive and Gram-negative strains.
Provides enzyme inhibition activity, as supported by IC50 values against E. coli DNA gyrase and E. coli Topo IV.
Includes clinical-strain potency reporting (MIC50/90 for Compound 7).
Includes hERG inhibition data with an associated safety/advantage narrative.
Documented Applications
Medicaments for inhibiting and/or killing microorganisms, including bacteria, virus, fungi, and protozoa, with particular emphasis on Gram-positive pathogens and Gram-negative pathogens.
Treatment of bacterial infections, including Gram-positive and Gram-negative bacterial infections.
Treatment of bacterial infections caused by listed bacterial species including Escherichia coli and Staphylococcus aureus, and additional listed species.
Pharmaceutical composition use as a medicament with a pharmaceutically acceptable carrier and optionally combined with at least one antibiotic.
Use as an antibacterial agent, supported by MIC measurements across Gram-positive and Gram-negative organisms listed in the MIC table.
Enzyme inhibition application involving inhibition of E. coli DNA gyrase and E. coli Topo IV, supported by IC50 values.
Clinical-strain antibacterial application, supported by MIC50/90 reporting for Compound 7.
hERG inhibition profiling application, supported by hERG inhibition IC50 values.
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