7, 8 and 9-substituted tetracycline compounds
View Patent ↗7, 8 and 9-substituted tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7, 8 and 9-substituted tetracycline compounds are described.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 4 and R 4′ are each methyl;
R 5 is hydrogen or hydroxyl;
R 6 and R 6′ are each independently hydrogen, methyl, or hydroxyl;
R 7 is hydrogen, lower alkenyl, lower alkynyl or acyl;
R 8 is hydrogen, phenyl, nitrophenyl, or lower alkynyl; and
R 9 is hydrogen; provided that at least one of R 7 or R 8 , is not hydrogen, or 8-bromo doxycycline or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 5 is hydroxyl, R 6 is methyl, and R 6′ is hydrogen.
3. The compound of claim 2 , wherein R 7 is ethenyl, ethynyl or acyl, and R 8 is hydrogen.
4. The compound of claim 3 , wherein said compound is 7-ethenyl doxycycline or 7-ethynyl doxycycline or a pharmaceutically acceptable salt thereof.
5. The compound of claim 3 , wherein said compound is 7-acyl doxycycline or 7-acetyl doxycycline or a pharmaceutically acceptable salt thereof.
6. The compound of claim 2 , wherein R 8 is phenyl, or nitrophenyl; and R 7 is hydrogen.
7. The compound of claim 6 , wherein said compound is 8-phenyl doxycycline or 8-(p-nitrophenyl) doxycycline or a pharmaceutically acceptable salt thereof.
8. The compound of claim 2 , wherein R 8 is phenyl or ethynyl.
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising a therapeutically effective amount of a compound and a pharmaceutically acceptable carrier, wherein said compound is selected from the group consisting of: 7-ethynyl doxycycline, 7-acyl doxycycline, 7-ethenyl doxycycline, 8-phenyl-9-amino doxycycline, 8-bromo doxycycline, 8-phenyl doxycycline, 8-(p-nitrophenyl) doxycycline, 7-acetyl doxycycline, 8-ethynyl-9-amino doxycycline and pharmaceutically acceptable salts thereof.
11. A method for treating a bacterial infection in a mammal, comprising administering to said mammal a compound of claim 1 .
12. A method for treating a bacterial infection in a mammal, comprising administering to said mammal a compound, wherein said compound is selected from the group consisting of: 7-ethynyl doxycycline, 7-acyl doxycycline, 7-ethenyl doxycycline, 8-phenyl-9-amino doxycycline, 8-bromo doxycycline, 8-phenyl doxycycline, 8-(p-nitrophenyl) doxycycline, 7-acetyl doxycycline, 8-ethynyl-9-amino doxycycline and pharmaceutically acceptable salts thereof.
13. The method of claim 11 , wherein said bacterial infection is associated with E. coli, S. aureus or E. faecalis.
14. The method of claim 12 , wherein said bacterial infection is associated with E. coli, S. aureus or E. faecalis.