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 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 halo substituted or unsubstituted phenyl;
and pharmaceutically acceptable salts 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 unsubstituted phenyl.
4. The compound of claim 3 , wherein said compound is 7-phenylsancycline.
5. The compound of claim 1 , wherein R 7 is 2-substituted phenyl.
6. The compound of claim 5 , wherein said compound is selected from the group consisting of 7-(2-fluorophenyl) sancycline, 7-(2-chlorophenyl) sancycline, 7-(2-bromophenyl) sancycline, and 7-(2-iodophenyl) sancycline.
7. The compound of claim 1 , wherein R 7 is 3-substituted phenyl.
8. The compound of claim 7 , wherein said compound is selected from the group consisting of 7-(3-fluorophenyl) sancycline, 7-(3-chlorophenyl) sancycline, 7-(3-bromophenyl) sancycline, and 7-(3-iodophenyl) sancycline.
9. The compound of claim 1 , wherein R 7 is 4-substituted phenyl.
10. The compound of claim 9 , wherein said compound is selected from the group consisting of 7-(4-fluorophenyl) sancycline, 7-(4-chlorophenyl) sancycline, 7-(4-bromophenyl) sancycline, 7-(4-iodophenyl) sancycline, 7-(4-trichloromethylphenyl) sancycline, 7-(4-trifluoromethylphenyl) sancycline, 7-(4-tribromomethylphenyl) sancycline, and 7-(4-triiodomethylphenyl) sancycline.
11. A method for treating a tetracycline responsive state 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 halo substituted or unsubstituted phenyl; and pharmaceutically acceptable salts thereof, such that the tetracycline responsive state is treated.
12. The method of claim 11 , wherein R 5 , R 6 and R 6′ are each hydrogen and R 4 and R 4′ are each methyl.
13. The method of claim 11 , wherein R 7 is unsubstituted phenyl.
14. The method of claim 13 , wherein said compound is 7-phenylsancycline.
15. The method of claim 11 , wherein R 7 is 2-substituted phenyl.
16. The method of claim 15 wherein said compound is selected from the group consisting of 7-(2-fluorophenyl) sancycline, 7-(2-chlorophenyl) sancycline, 7-(2-bromophenyl) sancycline, and 7-(2-iodophenyl) sancycline.
17. The method of claim 11 , wherein R 7 is 3-substituted phenyl.
18. The method of claim 17 , wherein said compound is selected from the group consisting of 7-(3-fluorophenyl) sancycline, 7-(3-chlorophenyl) sancycline, 7-(3-bromophenyl) sancycline, and 7-(3-iodophenyl) sancycline.
19. The method of claim 11 , wherein R 7 is 4-substituted phenyl.
20. The method of claim 19 , wherein said compound is selected from the group consisting of 7-(4-fluorophenyl) sancycline, 7-(4-chlorophenyl) sancycline, 7-(4-bromophenyl) sancycline, 7-(4-iodophenyl) sancycline, 7-(4-trichloromethylphenyl) sancycline, 7-(4-trifluoromethylphenyl) sancycline, 7-(4-tribromomethylphenyl) sancycline, and 7-(4-triiodomethylphenyl) sancycline.
21. The method of claim 11 , wherein said tetracycline responsive state is a bacterial infection.
22. The method of claim 21 , wherein said bacterial infection is associated with E. coli.
23. The method of claim 21 , wherein said bacterial infection is associated with S. aureus.
24. The method of claim 21 , wherein said bacterial infection is associated with E. faecalis.
25. The method of claim 21 , wherein said bacterial infection is resistant to other tetracycline antibiotics.
26. The method of claim 11 , wherein said compound is administered with a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
28. The pharmaceutical composition of claim 27 , wherein said compound is selected from the group consisting of 7-phenyl sancycline, 7-(2-fluorophenyl) sancycline, 7-(2-chlorophenyl) sancycline, 7-(2-bromophenyl) sancycline, 7-(2-iodophenyl) sancycline, 7-(3-fluorophenyl) sancycline, 7-(3-chlorophenyl) sancycline, 7-(3-bromophenyl) sancycline, 7-(3-iodophenyl) sancycline, 7-(4-fluorophenyl) sancycline, 7-(4-chlorophenyl) sancycline, 7-(4-bromophenyl) sancycline, 7-(4-iodophenyl) sancycline, 7-(4-trichloromethylphenyl) sancycline, 7-(4-trifluoromethylphenyl) sancycline, 7-(4-tribromomethylphenyl) sancycline, and 7-(4-triiodomethylphenyl) sancycline.
29. A tetracycline compound, wherein said compound is 7,9-diphenyl sancycline or a pharmaceutically acceptable salt thereof.
30. A method for treating a tetracycline responsive state in a mammal, comprising administering to said mammal an effective amount of 7,9-diphenyl sancycline or a pharmaceutically acceptable salt thereof, such that said mammal is treated.
31. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 29 and a pharmaceutically acceptable carrier.