Therapeutic uses of pharmaceutical compositions comprising cyclic boronic acid ester derivatives

A method of preparing a pharmaceutical composition for administration, comprising reconstituting the contents of a sterile container using a pharmaceutically acceptable diluent, wherein the sterile container comprises:

• an antibacterial agent in solid form;
• and
• a compound of Formula (I) in solid form having the structure:
• or a pharmaceutically acceptable salt thereof, wherein:
• Y is a 1-4 atom alkylene or 2-4 atom alkenylene linker, optionally substituted by one or more substituents selected from the group consisting of Cl, F, CN, CF3, —R9, —OR9, —C(═O)NR9R10, and —C(═O)OR9, wherein said alkylene or alkenylene linker is optionally fused to an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl;
• R1 is selected from a group consisting of —C1-9alkyl, —C2-9alkenyl, —C2-9alkynyl, —NR9R10, —C1-9alkylR11, —C2-9alkenylR11, —C2-9alkynylR11, -carbocyclyl-R11, —CH(OH)C1-9alkylR9, —CH(OH)C2-9alkenylR9, —CH(OH)C2-9alkynylR9, —CH(OH)carbocyclyl-R9, —C(═O)R9, —C(═O)C1-9alkylR9, —C(═O)C2-9alkenylR9, —C(═O)C2-9alkynylR9, —C(═O)C2-9carbocyclyl-R9, —C(═O)NR9R10, —N(R9)C(═O)R9, —N(R9)C(═O)NR9R10, —N(R9)C(═O)OR9, —N(R9)C(═O)C(═NR10)R9, —N(R9)C(═O)C(═CR9R10)R9, —N(R9)C(═O)C1-4alkylN(R9)C(═O)R9, —N(R9)C(═NR10)R9, —C(═NR10)NR9R10, —N═C(R9)NR9R10, —N(R9)SO2R9, —N(R9)SO2NR9R10, —N═CHR9, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl;
• R6 is selected from a group consisting of H, —C1-9alkyl, —C2-9alkenyl, —C2-9alkynyl, carbocyclyl, —C1-9alkylR11, —C2-9alkenylR11, —C2-9alkynylR11, -carbocyclyl-R11, —C(═O)OR9, —C1-9alkylCO2R9, —C2-9alkenylCO2R9, —C2-9alkynylCO2R9, and -carbocyclyl-CO2R9, or alternatively:
• (i) R6 and an R7 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or
• (ii) R6 is absent when the carbon to which it is attached is a ring atom in an aryl or heteroaryl ring;
• each R7 is independently selected from a group consisting of H, halo, —C1-9alkyl, —C2-9alkenyl, —C2-9alkynyl, —NR9R10, —OR9, —C1-9alkylCO2R9, —C2-9alkenylCO2R9, —C2-9alkynylCO2R9, and -carbocyclyl-CO2R9, or independently:
• (i) R6 and an R7 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl, or
• (ii) R7 and an R8 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl;
• each R8 is independently selected from a group consisting of H, halo, —C1-9alkyl, —C2-9alkenyl, —C2-9alkynyl, —NR9R10, —OR9, —C1-9alkylCO2R9, —C2-9alkenylCO2R9, —C2-9alkynylCO2R9, and -carbocyclyl-CO2R9, or independently:
• (i) an R7 and an R8 are taken together with the atoms to which they are attached to form an optionally substituted carbocyclyl or optionally substituted heterocyclyl,
• (ii) a geminal R7 and R8 together form —C2-9alkenylenylCO2R9, or
• (iii) each R8 attached to a ring atom forming part of an optionally substituted aryl is absent;
• each R9 is independently selected from a group consisting of H, —C1-9alkyl, —C2-9alkenyl, —C2-9alkynyl, carbocyclyl, —C1-9alkylR11, —C2-9alkenylR11, —C2-9alkynylR11, -carbocyclyl-R11, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —(CH2)0-3carbocyclyl, and optionally substituted heterocyclyl;
• each R10 is independently selected from a group consisting of H, —C1-9alkyl, —OR9, —CH(═NH), —C(═O)OR9, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl;
• each R11 is independently selected from a group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl;
• X is selected from a group consisting of —CO2R12 and a carboxylic acid isostere;
• R12 is selected from a group consisting of H, —C1-9alkyl, —(CH2)0-3—R11, —C(R13)2OC(O)C1-9alkyl, —C(R13)2OC(O)R11, —C(R13)2OC(O)OC1-9alkyl, and —C(R13)2OC(O)OR11;
• each R13 is independently selected from a group consisting of H and —C1-4alkyl;
• and
• m is independently zero or an integer from 1 to 2,
• wherein each —C1-9alkyl, —C2-9alkenyl, and —C2-9alkynyl is independently optionally substituted.