Antibacterial aminoglycoside analogs

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 hydrogen,

Q 2 is hydrogen, 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)NR 4 R 5 , —(CR 10 R 11 ) p R 12 ,

Q 3 is hydrogen, 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)NR 4 R 5 , —(CR 10 R 11 ) p R 12 ,

each R 1 , R 2 , R 3 , R 4 , R 5 , and R 10 is, independently, hydrogen or C 1 -C 6 alkyl, or R 1 and R 2 together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R 2 and R 3 together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms, or R 1 and R 3 together with the atoms to which they are attached can form a carbocyclic ring having from 4 to 6 ring atoms, or R 4 and R 5 together with the atom to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms;

each R 6 and R 7 is, independently, hydrogen, hydroxyl, amino or C 1 -C 6 alkyl, or R 6 and R 7 together with the atoms to which they are attached can form a heterocyclic ring having from 4 to 6 ring atoms;

each R 8 is hydrogen;

each R 9 is, independently, hydrogen or methyl;

each R 11 is, independently, hydrogen, hydroxyl, amino or C 1 -C 6 alkyl;

each R 12 is, independently, hydroxyl or amino;

each n is, independently, an integer from 0 to 4;

each m is, independently, an integer from 0 to 4; and

each p is, independently, an integer from 1 to 5, and

wherein (i) at least two of Q 1 , Q 2 and Q 3 are other than hydrogen, and (ii) if Q 1 is hydrogen, then at least one of Q 2 and Q 3 is —C(═NH)NR 4 R 5 .

2. A pharmaceutical composition of claim 1 wherein each R 9 is methyl.

3. A pharmaceutical composition of claim 1 wherein Q 1 and Q 2 are other than hydrogen.

4. A pharmaceutical composition of claim 3 wherein Q 3 is hydrogen.

5. A pharmaceutical composition of claim 3 wherein Q 1 is:

wherein:

R 1 is hydrogen;

R 2 is hydrogen; and

each R 3 is hydrogen.

6. A pharmaceutical composition of claim 5 wherein Q 1 is:

7. A pharmaceutical composition of claim 6 wherein Q 2 is —(CR 10 R 11 ) p R 12 .

8. A pharmaceutical composition of claim 7 wherein each R 10 is hydrogen.

9. A pharmaceutical composition of claim 8 wherein each R 11 is hydrogen.

10. A pharmaceutical composition of claim 3 wherein the compound is:

6′-(2-Hydroxy-ethyl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(4-amino-2(R)-hydroxy-butyryl)-sisomicin;

6′-(2-Hydroxy-propanol)-1-(4-amino-2(R)-hydroxy-butyryl)-sisomicin;

6′-(Methyl-piperidin-4-yl)-1-(4-amino-2(R)-hydroxy-butyryl)-sisomicin;

6′-(Methyl-cyclopropyl)-1-(4-amino-2(R)-hydroxy-butyryl)-sisomicin;

6′-(3-Amino-propyl)-1-(4-amino-2(R)-hydroxy-butyryl)-sisomicin;

6′-Methyl-cyclopropyl-1-(3-amino-2(R)-hydroxy-propionyl)-sisomicin;

6′-Methyl-piperidinyl-1-(3-amino-2(R)-hydroxy-propionyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(3-amino-2(R)-hydroxy-propionyl)-sisomicin;

6′-(2-Hydroxy-propanol)-1-(3-amino-2(R)-hydroxy-propionyl)-sisomicin;

6′-(3-Amino-propyl)-1-(3-amino-2(R)-hydroxy-propionyl)-sisomicin;

6′-(Methyl-piperidin-4-yl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(Methyl-cyclopropyl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(2-Hydroxy-propanol)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(Methyl-piperidin-4-yl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(3-Amino-propyl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(Methyl-cyclopropyl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(2-Hydroxy-propanol)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(3-Amino-2-hydroxy-propyl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(2-hydroxy-acetyl)-sisomicin;

6′-(3-Amino-propyl)-1-(2-amino-ethylsulfonamide)-sisomicin;

6′-(2-Hydroxy-propanol)-1-(2-amino-ethylsulfonamide)-sisomicin;

6′-(2(S)-Hydroxy-propanol)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(2-amino-ethylsulfonamide)-sisomicin;

6′-(Methyl-trans-3-amino-cyclobutyl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6′-(2-Hydroxy-4-amino-butyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6′-(Methyl-cyclopropyl)-1-(3-hydroxy-azetidin-3-yl-acetyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(3-hydroxy-azetidin-3-yl-acetyl)-sisomicin;

6′-(Methyl-(1-hydroxy-3-methylamino-cyclobutyl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(3-Amino-propyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6′-(Methyl-cyclopropyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6′-(2-Hydroxy-3-amino-propyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6′-(3-Amino-propyl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(Methyl-pyrrolidin-2-yl)-1-(4-amino-2(S)-hydroxy-butyryl)-sisomicin;

6′-(3-Amino-propyl)-1-(3-hydroxy-azetidin-3-yl-acetyl)-sisomicin;

6′-(3-Amino-propyl)-1-(1-hydroxy-3-amino-cyclobutyl-acetyl)-sisomicin;

6′-(Methyl-trans-3-amino-cyclobutyl)-1-(3-amino-2(S)-hydroxy-propionyl)-sisomicin;

6′-(Methyl-trans-3-amino-cyclobutyl)-1-(1-hydroxy-3-amino-cyclobutyl-acetyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(1-hydroxy-3-amino-cyclobutyl-acetyl)-sisomicin;

6′-Methylcyclopropyl-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin;

6′-(Methyl-trans-3-amino-cyclobutyl)-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin;

6′-(2-Hydroxy-ethyl)-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin;

6′-(3-Amino-propyl)-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin;

6′-(Methyl-trans-3-amino-cyclobutyl)-1-(3-hydroxy-pyrrolidin-3-yl-acetyl)-sisomicin;

6-(2-Hydroxy-3-amino-propyl)-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin; or

6′-(Methyl-3-amino-1-hydroxy-cyclobutyl)-1-(2-(azetidin-3-yl)-2-hydroxy-acetyl)-sisomicin.

11. A pharmaceutical composition of claim 1 wherein each R 9 is methyl.

12. A pharmaceutical composition of claim 11 wherein Q 3 is hydrogen.

13. A pharmaceutical composition of claim 12 wherein Q 1 is:

wherein:

R 1 is hydrogen;

R 2 is hydrogen; and

each R 3 is hydrogen.

14. A pharmaceutical composition of claim 13 wherein Q 1 is:

15. A pharmaceutical composition of claim 14 wherein Q 1 is:

16. A pharmaceutical composition of claim 15 wherein Q 2 is —(CR 10 R 11 ) p R 12 .

17. A pharmaceutical composition of claim 16 wherein each R 10 is hydrogen.

18. A pharmaceutical composition of claim 17 wherein each R 11 is hydrogen.

19. A pharmaceutical composition of claim 18 wherein p is 2.

20. A pharmaceutical composition of claim 1 wherein

Q 1 is

and

Q 2 is —(CR 10 R 11 ) p R 12 .

21. A pharmaceutical composition of claim 20 wherein each R 9 is methyl.

22. A pharmaceutical composition of claim 20 wherein Q 3 is hydrogen.

23. A pharmaceutical composition of claim 20 wherein R 1 is hydrogen, R 2 is hydrogen and each R 3 is hydrogen.

24. A pharmaceutical composition of claim 20 wherein n is 1 or 2.

25. A pharmaceutical composition of claim 23 wherein n is 1 or 2.

26. A pharmaceutical composition of claim 20 wherein each R 10 is hydrogen, each R 11 is hydrogen and R 12 is hydroxyl.

27. A pharmaceutical composition of claim 20 wherein p is 2.

28. A pharmaceutical composition of claim 26 wherein p is 2.

29. A pharmaceutical composition of claim 20 wherein R 1 is hydrogen, R 2 is hydrogen, each R 3 is hydrogen, each R 10 is hydrogen, each R 11 is hydrogen and R 12 is hydroxyl.

30. A pharmaceutical composition of claim 20 wherein n is 1 or 2, and p is 2.

31. A pharmaceutical composition of claim 29 wherein n is 1 or 2, and p is 2.

32. A pharmaceutical composition of claim 20 wherein Q 1 is: