7-N-substituted phenyl tetracycline compounds
View Patent ↗7-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted tetracycline compounds are described.
1. A 7-substituted tetracycline compound of the formula:
wherein:
R 4 and R 4′ are each alkyl;
R 5 is hydrogen, hydroxyl, or a prodrug moiety;
R 6 and R 6′ are each independently hydrogen, hydroxyl, alkyl, or taken together, alkenyl;
R 7 is an N-substituted phenyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 5 , R 6 and R 6′ are each hydrogen and R 4 and R 4′ are each methyl.
3. The compound of claim 1 , wherein R 7 is 2-N-substituted phenyl.
4. The compound of claim 3 , wherein R 7 is 2-nitrophenyl.
5. The compound of claim 3 , wherein R 7 is 2-aminophenyl.
6. The compound of claim 5 , wherein said 2-amino substituent is dialkylamino.
7. The compound of claim 1 , wherein R 7 is 3-N-substituted phenyl.
8. The compound of claim 7 , wherein R 7 is 3-nitrophenyl.
9. The compound of claim 7 , wherein R 7 is 3-aminophenyl.
10. The compound of claim 9 , wherein said 3-amino substituent is dialkylamino.
11. The compound of claim 10 , wherein said dialkyl amino group is dimethylamino.
12. The compound of claim 1 , wherein R 7 is 4-N-substituted phenyl.
13. The compound of claim 12 , wherein R 7 is 4-nitrophenyl.
14. The compound of claim 12 , wherein R 7 is 4-aminophenyl.
15. The compound of claim 14 , wherein said 4-amino substituent is dialkylamino.
16. The compound of claim 15 , wherein said dialkylamino group is dimethylamino.
17. The compound of claim 1 , wherein said compound is selected from the group consisting of: 7-(2-nitrophenyl)sancycline, 7-(2-aminophenyl)sancycline, 7-( 2 -N,N-dimethylaminophenyl)sancycline, 7-(2-N,N-diethylaminophenyl)sancycline, 7-(2-N,N-dipropylaminophenyl)sancycline, 7-(2-N,N-dibutylaminophenyl)sancycline, 7-(3-nitrophenyl)sancycline, 7-(3-aminophenyl)sancycline, 7-(3-N,N-dimethylaminophenyl)sancycline, 7-(3-N,N-diethylaminophenyl)sancycline, 7-(3-N,N-dipropylaminophenyl)sancycline, 7-(3-N,N-dibutylaminophenyl)sancycline, 7-(4-aminophenyl)sancycline, 7-(4-nitrophenyl)sancycline, 7-(4-N,N-diethylaminophenyl)sancycline, 7-(4-N,N-dipropylaminophenyl)sancycline, 7-(4-N,N-dibutylaminophenyl)sancycline and 7-(4-N,N-dimethylaminophenyl)sancycline.
18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
19. The pharmaceutical composition of claim 18 , wherein said compound is selected from the group consisting of 7-(2-aminophenyl)sancycline, 7-(2-nitrophenyl)sancycline, 7-(2-N,N-dimethylaminophenyl)sancycline, 7-(2-N,N-diethylaminophenyl)sancycline, 7-(2-N,N-dipropylaminophenyl)sancycline, 7-(2-N,N-dibutylaminophenyl)sancycline, 7-(3-aminophenyl)sancycline, 7-(3-nitrophenyl)sancycline, 7-(3-N,N-dimethylaminophenyl)sancycline, 7-(3-N,N-diethylaminophenyl)sancycline, 7-(3-N,N-dipropylaminophenyl)sancycline, 7-(3-N,N-dibutylaminophenyl)sancycline, 7-(4-aminophenyl)sancycline, 7-(4-nitrophenyl)sancycline, 7-(4-N,N-dimethylaminophenyl)sancycline, 7-(4-N,N-diethylaminophenyl)sancycline, 7-(4-N,N-dipropylaminophenyl)sancycline, and 7-(4-N,N-dibutylaminophenyl)sancycline.
20. A method for treating a bacterial infection in a mammal, comprising administering to said mammal a 7-substituted tetracycline compound of formula (I):
wherein:
R 4 and R 4′ are each alkyl;
R 5 is hydrogen, hydroxyl, or a prodrug moiety;
R 6 and R 6′ are each independently hydrogen, hydroxyl, alkyl, or taken together, alkenyl;
R 7 is an N-substituted phenyl;
or a pharmaceutically acceptable salt thereof,
such that the bacterial infection is treated.
21. The method of claim 20 , wherein said compound is selected from the group consisting of: 7-(2-aminophenyl)sancycline, 7-(2-nitrophenyl)sancycline, 7-(2-N,N-dimethylaminophenyl)sancycline, 7-(2-N,N-diethylaminophenyl)sancycline, 7-(2-N,N-dipropylaminophenyl)sancycline, 7-(2-N,N-dibutylaminophenyl)sancycline, 7-(3-nitrophenyl)sancycline, 7-(3-aminophenyl)sancycline, 7-(3-N,N-dimethylaminophenyl)sancycline, 7-(3-N,N-diethylaminophenyl)sancycline, 7-(3-N,N-dipropylaminophenyl)sancycline, 7-(3-N,N-dibutylaminophenyl)sancycline, 7-(4-N,N-dimethylaminophenyl)sancycline, 7-(4-aminophenyl)sancycline, 7-(4-nitrophenyl)sancycline, 7-(4-N,N-diethylaminophenyl)sancycline, 7-(4-N,N-dipropylaminophenyl)sancycline and 7-(4-N,N-dibutylaminophenyl)sancycline.
22. The method of claim 20 , wherein said bacterial infection is associated with E. coli.
23. The method of claim 20 , wherein said bacterial infection is associated with S. aureus.
24. The method of claim 20 , wherein said bacterial infection is associated with E. faecalis.
25. The method of claim 20 , wherein said bacterial infection is resistant to other tetracycline antibiotics.
26. The method of claim 20 , wherein said compound is administered with a pharmaceutically acceptable carrier.