ExoVII inhibitor and quinolone antibiotic combination useful for treating bacterial infection

A method of treating a bacterial infection in a subject comprising administering a therapeutically effective amount of a combination of a bacterial type IIA topoisomerase inhibitor, or a pharmaceutically acceptable salt thereof and a compound Formula I, or a pharmaceutically acceptable salt thereof, to the subject, where the compound of Formula I is

• Y1 is carbon substituted with oxo and Y2 is CR6;
• or
• Y1 is CR5 and Y2 is carbon substituted with oxo;
• R1, R3, and R4 are independently chosen from H, halogen, hydroxyl, amino, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, and C1-C2haloalkoxy;
• R2 is H, halogen, hydroxyl, amino, nitro, cyano, —COOH, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, or C1-C2haloalkoxy;
• or
• R2 is —C0-C2alkyl (C3-C2cycloalkyl), —C0-C2alkyl (aryl), —C0-C2alkyl (pyridyl), or —C0-C2alkyl (furanyl), each of which is optionally substituted with one or more substituents independently chosen from R10,
• R4 is H, halogen, hydroxyl, amino, nitro, cyano, C1-C4alkyl, C1-C4alkoxy, C2-C6alkanoyl, —C1-C6alkylester, —C0-C4alkyl (mono- or di-C1-C6alkylamino), mono- or di-C1-C6alkylcarboxamide;
• C1-C2haloalkyl, or C1-C2haloalkoxy;
• R5 and R6 are independently chosen from H, halogen, hydroxyl, amino, nitro, cyano, —CHO, —COOH, —CONH3, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, C2-C6alkanoyl, C1-C6alkylester, —C0-C4alkyl (mono- and di-C1-C6alkylamino), and mono- and di-(C1-C6alkyl) carboxamide;
• R10 is independently selected at each occurrence from halogen, hydroxyl, amino, nitro, cyano, —CHO, —COOH, oxo, C1-C8alkyl, C2-C8alkenyl, and C2-C8alkynyl, wherein in each C1-C8alkyl, C2-C8alkenyl, and C2-C8alkynyl, in the definition of R10 one or more carbon atoms is optionally replaced by O, NR11, —C(O)—, —NR11C(O)—, —C(O)NR11—, —C(O)O—, —OC(O)—, —S(O)n—, —S(O)nNR11—, or —NR11S(O)n—, where n is 0, 1, or 2, and in which each C0-C4alkyl, C1-C8alkyl, C2-C8alkenyl, or C2-C8alkynyl is optionally substituted with one or more substituents R13;
• R11 is independently chosen at each occurrence from hydrogen, C1-C6alkyl, and —C0-C2alkyl (C3-C2cycloalkyl);
• and
• R13 is independently chosen at each occurrence from halogen, hydroxyl, amino, nitro, cyano, —CHO, —COOH, oxo, C3-C7cycloalkyl, and phenyl.