Antibacterial aminoglycoside analogs
View Patent ↗Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Q 1 and Q 2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, diluent or excipient and a compound having the following structure (I):
or a stereoisomer or pharmaceutically acceptable salt thereof,
wherein:
Q 1 is —NHR 1 ;
Q2 is
R 1 is C 2 -C 6 alkyl substituted with one or two hydroxyl groups;
R 2 is hydrogen or C 1 -C 6 alkyl optionally substituted with one or more halogen, hydroxyl or amino; and
n is an integer from 1 to 4.
2. A pharmaceutical composition according to claim 1 , wherein R 1 is C 2 -C 6 alkyl substituted with one hydroxyl group.
3. A pharmaceutical composition according to claim 2 , wherein R 1 is —(CH 2 ) m OH, wherein m is an integer from 2 to 6.
4. A pharmaceutical composition according to claim 3 , wherein R 1 is —(CH 2 ) 2 OH or —(CH 2 ) 3 OH.
5. A pharmaceutical composition according to claim 4 , wherein R 1 is —(CH 2 ) 2 OH.
6. A pharmaceutical composition according to claim 2 , wherein R 1 is —(CH 2 ) p CH(CH 3 )OH, wherein p is an integer from 1 to 4.
7. A pharmaceutical composition according to claim 6 , wherein R 1 is —CH 2 CH(CH 3 )OH or —(CH 2 ) 2 CH(CH 3 )OH.
8. A pharmaceutical composition according to claim 1 , wherein R 1 is C 2 -C 6 alkyl substituted with two hydroxyl groups.
9. A pharmaceutical composition according to claim 8 , wherein R 1 is —CH 2 CH(OH)(CH 2 ) q OH wherein q is an integer from 1 to 4.
10. A pharmaceutical composition according to claim 9 , wherein R 1 is —CH 2 CH(OH)CH 2 OH or —CH 2 CH(OH)(CH 2 ) 2 OH.
11. A pharmaceutical composition according to claim 8 , wherein R 1 is —(CH 2 ) r CH(CH 2 OH) 2 wherein r is 0 or an integer from 1 to 3.
12. A pharmaceutical composition according to claim 11 , wherein R 1 is —CH 2 CH(CH 2 OH) 2 or —CH(CH 2 OH) 2 .
13. A pharmaceutical composition according to claim 12 , wherein R 2 is hydrogen.
14. A pharmaceutical composition according to claim 13 , wherein Q 2 is:
15. A pharmaceutical composition according to claim 14 , wherein Q 2 is:
16. A pharmaceutical composition according to claim 14 , wherein Q 2 is:
17. A pharmaceutical composition according to claim 1 , wherein said compound has the configuration:
18. A pharmaceutical composition according to claim 1 , wherein said compound is:
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition according to claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
20. A pharmaceutical composition according to claim 18 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.