COMPOUNDS USEFUL AS ANTIBIOTIC TOLERANCE INHIBITORS

摘要

The disclosure provides compounds and pharmaceutical compositions of the compounds useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds and salts of general Formula VIII Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a patient, including Pseudomonas aeruginosa infections, are also provided by the disclosure.;

主权项

1. A method for treating a bacterial infection in a subject comprising administering to the subject a composition comprising a compound of Formula VIII:or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier, wherein:
each of R20 and R21 is independently selected from hydrogen, chloro, fluoro, bromo, cyano, —OCHF2, and CF3, wherein at least one of R20 or R21 is other than hydrogen; R22 is selected from hydrogen, chloro, fluoro, bromo, methyl, ethyl, —OCH3, —OCH2CH3, CF3, and CHF2 Y1 is selected from NH, O and S; Z is selected from CH2, NH and S; R23 is selected from hydrogen, chloro, fluoro, bromo, methyl, ethyl, hydroxy, —OCH3, —OCH2CH3, CF3, and CHF2 R24 is selected from chloro, fluoro, bromo, cyano, —OCH3, optionally substituted pyridinyloxy, optionally substituted pyrimidinyloxy, optionally substituted pyrazinyloxy, and optionally substituted pyridazinyl; each R25 is independently selected from hydrogen, hydroxy, halogen, C1-C4 alkyl, and C1-C4 haloalkyl; R9b, if present, is selected from bromo, chloro and fluoro, wherein:when R24 is optionally substituted pyridinyloxy, optionally substituted pyrimidinyloxy, optionally substituted pyrazinyloxy, or optionally substituted pyridazinyl, Z is S and Y1 is NH, then each of R20 and R21 is other than hydrogen or cyano.