Back to results
US 8,524,689 B2Granted
Antibacterial aminoglycoside analogs
AssigneeAchaogen, Inc.
InventorsAdam Aaron Goldblum, Paola Dozzo, James Bradley Aggen, Martin Sheringham Linsell
Life of this patent
Estimating the term…
Abstract
Compounds having antibacterial activity are disclosed. The compounds have the following structure (I) or (II): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q3, R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Claims20
A compound having the following structure (I):
- or a stereoisomer or pharmaceutically acceptable salt thereof,
- wherein:
- Q1 is
- Q2 is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR7R8,
- Q3 is hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR7R8,
- each R1 and R2 is, independently, hydrogen or an amino protecting group;
- each R3 is, independently, hydrogen or a hydroxyl protecting group;
- each R4, R5, R7 and R8 is, independently, hydrogen or C1-C6 alkyl optionally substituted with one or more halogen, hydroxyl or amino;
- each R6 is, independently, hydrogen, halogen, hydroxyl, amino or C1-C6 alkyl;
- or R4 and R5 together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R5 and one R6 together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms, or R4 and one R6 together with the atoms to which they are attached can form a carbocyclic ring having from 3 to 6 ring atoms, or R7 and R8 together with the atom to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms;
- each R9 is, independently, hydrogen, hydroxyl, amino or C1-C6 alkyl optionally substituted with one or more halogen, hydroxyl or amino;
- each R10 is, independently, hydrogen, halogen, hydroxyl, amino or C1-C6 alkyl;
- or R9 and one R10 together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms;
- and
- each n is, independently, an integer from 0 to 4, and
- wherein (i) at least one of Q2 and Q3 are other than hydrogen, and (ii) if Q1 is —C(═O)CH(OH)CH2NH2, —C(═O)CH(OH)(CH2)2NH2, or —C(═O)CH(OH)(CH2)3NH2, then Q2 is not methyl or —C(═O)OC(CH3)3, and (iii) if Q1 is —C(═O)CH(OH)CH2NH2 or —C(═O)CH(OH)(CH2)2NH2, then Q3 is not —C(═O)OC(CH3)3, —C(═O)OCH2Ph, —C(═O)CH(OH)CH2NH2 or —C(═O)CH(OH)(CH2)2NH2.
13 more elements
A compound having the following structure (II):
- or a stereoisomer or pharmaceutically acceptable salt thereof,
- wherein:
- Q1 is
- Q2 is optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —C(═NH)NR7R8,
- each R1 and R2 is, independently, hydrogen or an amino protecting group;
- each R3 is, independently, hydrogen or a hydroxyl protecting group;
- each R4, R5, R7 and R8 is, independently, hydrogen or C1-C6 alkyl optionally substituted with one or more halogen, hydroxyl or amino;
- each R6 is, independently, hydrogen, halogen, hydroxyl, amino or C1-C6 alkyl;
- or R4 and R5 together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R5 and one R6 together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms, or R4 and one R6 together with the atoms to which they are attached can form a carbocyclic ring having from 3 to 6 ring atoms, or R7 and R8 together with the atom to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms;
- each R9 is, independently, hydrogen, hydroxyl, amino or C1-C6 alkyl optionally substituted with one or more halogen, hydroxyl or amino;
- each R10 is, independently, hydrogen, halogen, hydroxyl, amino or C1-C6 alkyl;
- or R9 and one R10 together with the atoms to which they are attached can form a heterocyclic ring having from 3 to 6 ring atoms;
- and
- each n is, independently, an integer from 0 to 4, and
- wherein (i) if Q1 is —C(═O)CHOH(CH2)2NHR5, then Q2 is not optionally substituted alkyl, and (ii) if Q1 is —C(═O)CH(OH)(CH2)2NHC(═NH)NH2, —C(═O)CH(CH3)CH2NH2, —CH2CH(OH)(CH2)2NH2, —C(═O)CH(OH)CH2NH2, —C(═O)CH(OH)(CH2)2NH2, —C(═O)CH(OH)(CH2)3NH2, or —C(═O)CHF(CH2)2NH2, then Q2 is not methyl, ethyl, —CH(═NH), —C(CH3)(═NH), —C(═NH)NH2, —C(═O)CH3, —C(═O)(CH2)2CO2H, —C(═O)CH(OH)(CH2)2NH2,
12 more elements
Dependencies are inferred from the claim text.