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US 8,524,675 B2Granted
Antibacterial aminoglycoside analogs
AssigneeAchaogen, Inc.
InventorsPaola Dozzo, Adam Aaron Goldblum, 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, R3, R11 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 alkyl optionally substituted with hydroxyl or amino,
- 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;
- each R11 is, independently, hydrogen or methyl;
- and
- n is 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 methyl, ethyl, i-propyl, i-butyl, —(CH2)2OH, —CH2CH(OH)(CH2)2NH2, —C(=O)H, —C(=O)CH(OH)CH2NH2, —C(=O)CH(OH)(CH2)2NH2, —C(=O)CH(OH)(CH2)3NH2, —C(=O)CH(OH)(CH2)4NH2, —C(=O)N(OH)(CH2)2NH2, —C(=O)CH2NH2, —C(=O)(CH2)4NH2—C(=O)CH2NHC(CH3)3, —C(=O)CH(CH(CH2)2)NH2, —C(=O)CHNH2(CH2)4NH2, —C(=O)(CH2)2C(CH3)2CH(CH3)OH, —C(=O)CH(OH)CH2NH2, —C(=O)OC(CH3)3, —C(=O)(CH2)4OH, —C(=O)CH3 or —C(=O)NH(CH2)2NH2, then Q2 is not methyl, and (iii) if Q1 is —C(=O)CH(OH)(CH2)2NH2, then Q3 is not —C(=O)CH(OH)(CH2)2NH2.
14 more elements
A compound having the following structure (II):
- or a stereoisomer or pharmaceutically acceptable salt thereof,
- wherein:
- Q1 is optionally substituted alkyl,
- 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-C6alkyl optionally substituted with one or more halogen, hydroxyl or amino;
- each R6is, independently, hydrogen, halogen, hydroxyl, amino or C1-C6alkyl;
- 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-C6alkyl;
- or R9and 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 if Q1 is —C(=O)CH3, —C(=O)CH(OH)CH2NH2, —C(=O)CH(OH)CH2NH2 or —C(=O)CH(OH)(CH2)2NH2, then Q2 is not methyl, —C(=O)CH(OH)CH2NH2, —C(=O)OH(CH3)3 or
12 more elements
Dependencies are inferred from the claim text.