7-phenyl-substituted tetracycline compounds
View Patent ↗7-phenyl-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-phenyl-substituted tetracycline compounds are described.
1. A compound of 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 dihalo substituted or trihalo 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 difluoro substituted phenyl.
4. The compound of claim 1 , wherein R 7 is dichloro substituted phenyl.
5. The compound of claim 1 , wherein R 7 is dibromo substituted phenyl.
6. The compound of claim 1 , wherein R 7 is diiodo substituted phenyl.
7. The compound of claim 1 , wherein R 7 is 2,4-dihalo substituted phenyl.
8. The compound of claim 7 , wherein said compound is selected from the group consisting of 7-(2,4-difluorophenyl)sancycline, 7-(2,4-dichlorophenyl) sancycline, 7-(2,4-dibromophenyl)sancycline, and 7-(2,4-diiodophenyl)sancycline.
9. The compound of claim 8 , wherein said compound is 7-(2,4-difluorophenyl)sancycline.
10. The compound of claim 1 , wherein R 7 is 2,6-dihalo substituted phenyl.
11. The compound of claim 10 , wherein said compound is selected from the group consisting of 7-(2,6-difluorophenyl)sancycline, 7-(2,6-dichlorophenyl) sancycline, 7-(2,6-dibromophenyl)sancycline, and 7-(2,6-diiodophenyl)sancycline.
12. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
13. A compound selected from the group consisting of: 7-(2,4-difluorophenyl)sancycline, 7-(2,4-dichlorophenyl)sancycline, 7-(2,4-dibromophenyl) sancycline, 7-(2,4-diiodophenyl)sancycline, 7-(2,6-difluorophenyl)sancycline, 7-(2,6-dichlorophenyl)sancycline, 7-(2,6-dibromophenyl)sancycline, 7-(2,6-diiodophenyl)sancycline and pharmaceutically acceptable salts thereof.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 13 and a pharmaceutically acceptable carrier.
15. 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 dihalo substituted or trihalo substituted phenyl; or a pharmaceutically acceptable salt thereof, such that the bacterial infection is treated.
16. The method of claim 15 , wherein R 5 , R 6 and R 6′ are each hydrogen and R 4 and R 4′ are each methyl.
17. The method of claim 15 , wherein said bacterial infection is associated with E. coli.
18. The method of claim 15 , wherein said bacterial infection is associated with S. aureus.
19. The method of claim 15 , wherein said bacterial infection is associated with E. faecalis.
20. The method of claim 15 , wherein said compound is administered with a pharmaceutically acceptable carrier.