Antibacterial 4,5-substituted aminoglycoside analogs having multiple substituents
View Patent ↗The present invention is directed to analogs of aminoglycoside compounds as well as their preparation and use as prophylactic or therapeutics against microbial infection.
1. A compound having the following formula VI:
or a prodrug or pharmaceutically acceptable salt thereof,
wherein:
Q1 is —NR 10 R 11 ;
Q 2 is
each Q 3 and Q 4 is —OR 7 ;
Q 5 is —OR 8 ;
each of R 1 , R 6 , R 7 and R 8 is, in each instance, H;
each R 2 and R 10 is, independently, H, C 1 -C 12 alkyl or substituted C 1 -C 12 alkyl;
R 11 is cyano, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl or —(CH 2 ) n -(L 1 ) m -(CH 2 ) nn -E 1 ;
L 1 is S, O or NJ 1 ;
n is an integer from 1 to 8;
m is 0 or 1;
nn is 0 or an integer from 1 to 8;
mm is 1 or 2;
E 1 is H, hydroxyl, halogen, cyano, —NJ 1 J 2 , C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl, C 5 -C 20 aryl, substituted C 5 -C 20 aryl, heteroaryl, substituted heteroaryl, a heterocyclic radical, a substituted heterocyclic radical or a substituted or unsubstituted mono or poly cyclic structure that is unsaturated, partially saturated or fully saturated and optionally includes one or more heteroatoms selected from O, N and S;
each J 1 and J 2 is, independently, H, C 1 -C 12 alkyl, substituted C 1 -C 12 alkyl, C 2 -C 12 alkenyl, substituted C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, substituted C 2 -C 12 alkynyl, C 5 -C 20 aryl, substituted C 5 -C 20 aryl, —C(═O)—X, a heterocyclic radical or a substituted heterocyclic radical;
each X is, independently, H, C 1 -C 12 alkyl or substituted C 1 -C 12 alkyl; and
Z 1 and Z 2 are each, independently, H or —OH.
2. A compound according to claim 1 , wherein mm is 1.
3. A compound according to claim 1 , wherein mm is 2.
4. A compound according to claim 1 , wherein each R 2 is H.
5. A compound according to claim 1 , wherein Z 1 is —OH.
6. A compound according to claim 1 , wherein R 10 is H.
7. A compound according to claim 6 , wherein R 11 is substituted C 1 -C 12 alkyl.
8. A compound according to claim 1 , wherein:
R 10 is H;
R 11 is substituted C 1 -C 12 alkyl;
each R 2 is H; and
Z 1 is —OH.
9. A compound according to claim 8 , wherein mm is 1.
10. A compound according to claim 8 , wherein mm is 2.
11. A compound according to claim 1 having the configuration:
12. A compound according to claim 11 , wherein mm is 1.
13. A compound according to claim 11 , wherein mm is 2.
14. A compound according to claim 11 , wherein each R 2 is H.
15. A compound according to claim 11 , wherein Z 1 is —OH.
16. A compound according to claim 11 , wherein R 10 is H.
17. A compound according to claim 16 , wherein R 11 is substituted C 1 -C 12 alkyl.
18. A compound according to claim 11 , wherein:
R 10 is H;
R 11 is substituted C 1 -C 12 alkyl;
each R 2 is H; and
Z 1 is —OH.
19. A compound according to claim 18 , wherein mm is 1.
20. A compound according to claim 18 , wherein mm is 2.