9-aminoacyl tetracycline compounds and methods of use thereof
View Patent ↗A compound of formula (I):
1. A compound of formula (I):
wherein:
R represents hydrogen, halogen or C 1-6 alkyl;
R 1 represents hydrogen, C 1 alkyl or together R 1 and R 3 represent a CH 2 moiety;
R 2 represents hydrogen, —OC 1-6 alkyl, —O(O)C 1-6 alkyl or hydroxy;
R 3 represents hydrogen, hydroxy or together R 3 and R 1 represent a CH 2 moiety;
R 4 represents hydrogen or C 1-6 alkyl;
R 5 represents hydrogen, C 1-6 alkyl or C 1-6 alkoxycarbonyl;
X represents NRxRy;
Rx and Ry represent —C 1-6 alkylheterocycle or together Rx and Ry form a heterocycle; and pharmaceutically acceptable salts thereof.
2. A method for the treatment of a bacterial infection in a subject, which comprises administering to the subject an effective amount of a compound of formula (I):
wherein:
R represents hydrogen) halogen, or C 1-6 alkyl;
R 1 represents hydrogen, C 1-6 alkyl or together R 1 and R 3 represent a CH 2 moiety;
R 2 represents hydrogen, —OC 1-6 alkyl, —O(O)C 1-6 alkyl or hydroxy;
R 3 represents hydrogen, hydroxy or together R 3 and R 1 represent a CH 2 moiety;
R 4 represents hydrogen or C 1-6 alkyl;
R 5 represents hydrogen, C 1-6 alkyl or C 1-6 alkoxycarbonyl;
X represents NRxRy;
Rx and Ry represent —C 1-6 alkylheterocycle or together Rx and Ry form a heterocycle; and pharmaceutically acceptable salts thereof.
3. The method of claim 2 , wherein said subject is a human.
4. A pharmaceutical formulation comprising a compound of formula (I):
wherein:
R represents hydrogen) halogen, or C 1-6 alkyl;
R 1 represents hydrogen, C 1-6 alkyl or together R 1 and R 3 represent a CH 2 moiety;
R 2 represents hydrogen, —OC 1-6 alkyl, —O(O)C 1-6 alkyl or hydroxy;
R 3 represents hydrogen, hydroxy or together R 3 and R 1 represent a CH 2 moiety;
R 4 represents hydrogen or C 1-6 alkyl;
R 5 represents hydrogen, C 1-6 alkyl or C 1-6 alkoxycarbonyl;
X represents NRxRy;
Rx and Ry represent —C 1-6 alkylheterocycle or together Rx end Ry form a heterocycle; and pharmaceutically acceptable salts thereof; and one or more pharmaceutically acceptable carriers.
5. The compound of claim 1 , wherein said compound is [4S -(4a,5,5a,6,12a)]-4-(Dimethylamino)-9-[(-pyrrolidinocarbonyl)methyl]amino -1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.
6. The compound of claim 1 , wherein said compound is [4S -(4a,5,5a,6,12a)]-4-(Dimethylamino)-9-[(1-piperidinocarbonyl)methyl]amino -1,4,4a5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl -1,11-dioxo-2-naphthacenecarboxamide.
7. The compound of claim 1 , wherein said compound is [4S -(4a,5a,12a)]-4-(Dimethylamino)-9-[(1-pyrrolidinoaminocarbonyl)methyl]amino -1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide.
8. The method of claim 2 , wherein said compound is [4S -(4a,5,5a,6,12a)]-4-(Dimethylamino)-9-[(1-pyrrolidinocarbonyl)methyl]amino -1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.
9. The method of claim 2 , wherein said compound is [4S -(4a,5,5a,6,11,12a)]-4-(Dimethylamino)-9-[(1-piperidinocarbonyl)methyl]amino -1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.
10. The method of claim 2 , wherein said compound is [4S -(4a,5a,12a)]-4-(Dimethylamino)-9-[(1-pyrrolidinoaminocarbonyl)methyl]amino -1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide.
11. The pharmaceutical formulation of claim 4 , wherein said compound is [4S-(4a,5,5a,6,12a)]-4-(Dimethylamino)-9-[(1-pyrrolidinocarbonyl)methyl]amino-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a -pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.
12. The pharmaceutical formulation of claim 4 , wherein said compound is [4S-(4a,5,5a,6,12a)]-4-(Dimethylamino)-9-[( 1-piperidinocarbonyl)methyl]amino1,4,4a,5,5a,6,11,12a-octahydro-3,5, 10,12,12a -pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.
13. The pharmaceutical formulation of claim 6 , wherein said compound is [4S-(4a,5a,12a)]-4-(Dimethylamino)-9-[(1-pyrrolidinoaminocarbonyl)methyl]amino-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a -tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide.
14. The method of claim 2 , wherein said bacterial infection is a gram positive bacterium.
15. The method of claim 2 , wherein said bacterial infection is a gram negative bacterium.
16. The method of claim 2 , wherein said bacterial infection is S. pneumoniae or S. aureus.
17. The method of claim 2 , wherein said bacterial infection is H. influenzae, M catarrhalis or E coli.