发明名称 CYCLIC BORONIC ACID ESTER DERIVATIVES AND THERAPEUTIC USES THEREOF
摘要 Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to cyclic boronic acid ester derivatives and their use as therapeutic agents.
申请公布号 US2016220591(A1) 申请公布日期 2016.08.04
申请号 US201615015002 申请日期 2016.02.03
申请人 Rempex Pharmaceuticals, Inc. 发明人 Hirst Gavin;Reddy Raja;Hecker Scott;Totrov Maxim;Griffith David C.;Rodny Olga;Dudley Michael N.;Boyer Serge
分类号 A61K31/69;A61K9/00;A61K31/427;A61K31/407;A61K31/546;A61K31/4196 主分类号 A61K31/69
代理机构 代理人
主权项 1. A method of treating or preventing a bacterial infection comprising administering to a subject in need thereof an effective amount of a compound having the structure of formula (I): 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;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, 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, 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 a substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl, or(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;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, -carbocyclyl-CO2R9, or independently: (i) 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-C2-9alkenylenylCO2R9, 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 C1-4alkyl; andm is independently zero or an integer from 1 to 2,wherein each C1-9alkyl, C2-9alkenyl, and C2-9alkynyl is independently optionally substituted.
地址 San Diego CA US