Substituted tetracycline compounds
The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds such as blocking tetracycline efflux and modulation of gene expression.
1. A compound of Formula (III):
wherein
R 9 is R 9a R 9b NC(═O) or cyclopropyl;
R 10 is hydrogen or alkenyl;
R 9a is hydrogen or alkyl; and
R 9b is hydrogen, alkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkylcarbonylaminoalkyl, alkoxycarbonylalkyl, aryl, cycloalkyl or aminoalkyl;
or a pharmaceutically acceptable salt, ester or prodrug thereof.
2. The compound of claim 1 , wherein R 10 is alkenyl.
3. The compound of claim 1 , wherein R 10 is hydrogen.
4. The compound of claim 3 , wherein R 9 is R 9a R 9b NC(═O)—.
5. The compound of claim 4 , wherein R 9a and R 9b are each methyl or ethyl.
6. The compound of claim 4 , wherein R 9a is alkyl.
7. The compound of claim 4 , wherein R 9b is alkoxyalkyl.
8. The compound of claim 4 , wherein R 9a is hydrogen.
9. The compound of claim 8 , wherein R 9b is hydrogen, hydroxy, alkoxy, hydroxyalkyl, alkyl, cycbalkyl, alkylcarbonylaminoalkyl, alkoxycarbonylalkyl, aryl or aminoalkyl.
10. The compound of claim 1 , which is selected from the group consisting of:
and pharmaceutically acceptable salts, esters and prodrugs thereof.
11. The compound of claim 10 , wherein said compound is
or a pharmaceutically acceptable salt thereof.
12. A compound, which is:
or a pharmaceutically acceptable salt thereof.
13. A compound, which is:
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.