Cyclic boronic acid ester derivatives and therapeutic uses thereof

A compound having the structure of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Y is a 1-4 atom alkylene, 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 —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)C1-9 alkylR9, —C(═O)C2-9alkenylR9, —C(═O)C2-9alkynylR9, —C(═O)C2-9-carbocyclyl-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, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted 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 a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl,
• (ii) R6 and a carbon atom in Y are taken together with intervening atoms to form a substituted or unsubstituted carbocyclyl or substituted or unsubstitued heterocyclyl, or
• (iii) 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:
• R6 and an R7 are taken together with the atoms to which they are attached to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl,
• (ii) R7 and an R8 are taken together with the atoms to which they are attached to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl,
• (iii) an R7 and a carbon atom in Y are taken together with intervening atoms to form a substituted or unsubstituted carbocyclyl or substituted or unsubstitued heterocyclyl,
• (iv) each of the following conditions are met:
• (a) Y is a 3-4 atom alkylene or 3-4 atom alkenylene linker,
• (b) R6 is absent,
• (c) R7 and a carbon atom in Y are taken together with intervening atoms to form a substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl, and
• (d) each R8 attached to a ring atom forming part of the substituted or unsubstituted aryl or a substituted or unsubstituted heteroaryl formed by R7 and Y is absent;
• each R8 is independently selected from a group consisting of H, halo, —C2-9alkenyl, —C2-9alkynyl, —NR9R10, —OR9, —C1-9alkylCO2R9, —C2-9alkenylCO2R9, —C2-9alkynylCO2R9, -carbocyclyl-CO2R9, or independently:
• an R7 and an R8 are taken together with the atoms to which they are attached to form a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl,
• (ii) a geminal R7 and R8 together form —C2-9 alkenylenylCO2R9, or
• (iii) each R8 attached to a ring atom forming part of a substituted or unsubstituted 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, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• each R10 is independently selected from a group consisting of H, —C1-9alkyl, —OR9, —CH(═NH), —C(═O)OR9, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• each R11 is independently selected from a group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• X is selected from a group consisting of —CO2R12, and carboxylic acid isosteres;
• 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 C1-4-alkyl;
• and
• m is independently an integer from 1 to 2,
• wherein each C1-9alkyl, C2-9alkenyl, and C2-9alkynyl is independently optionally substituted.