PRODRUGS OF 9-AMINOMETHYL TETRACYCLINE COMPOUNDS
The invention pertains to prodrugs of 9-aminomethyl substituted tetracycline compounds, methods of using the compounds, and pharmaceutical compositions containing them.
1 . A compound of the formula (I):
wherein
E is oxygen, nitrogen, or a covalent bond;
G is alkyl; heterocyclicalkyl; aryl; alkylcarbonyloxyalkyl; arylcarbonyloxyalkyl; alkyloxycarbonyloxyalkyl; arylalkylcarbonyloxyalkyl; alkyloxyalkylcarbonyloxyalkyl; alkoxyalkoxycarbonyloxyalkyl, and pharmaceutically acceptable salts thereof.
2 . The compound of claim 1 , wherein E is a covalent bond.
3 . The compound of claim 2 , wherein G is alkyl.
4 . The compound of claim 1 , wherein E is nitrogen.
5 . The compound of claim 4 , wherein G is aryl.
6 . The compound of claim 5 , wherein G is substituted phenyl.
7 . The compound of claim 1 , wherein E is oxygen.
8 . The compound of claim 7 , wherein G is alkylcarbonyloxyalkyl.
9 . A compound of the formula (II):
wherein
Q′ is a prodrug moiety and pharmaceutically acceptable salts thereof.
10 . The compound of claim 9 , wherein Q′ is of the formula
—(C═O)-E 1 -G 1
wherein
E′ is oxygen, nitrogen, or a covalent bond;
G′ is alkyl; heterocyclicalkyl; aryl; alkylcarbonyloxyalkyl; arylcarbonyloxyalkyl; alkyloxycarbonyloxyalkyl; arylalkylcarbonyloxyalkyl; alkyloxyalkylcarbonyloxyalkyl; or alkoxyalkoxycarbonyloxyalkyl.
11 . The compound of claim 10 , wherein E 1 is oxygen.
12 . The compound of claim 11 , wherein G 1 is alkylcarbonyloxyalkyl.
13 . A compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
14 . A method for treating a tetracycline responsive state in a subject, comprising administering to said subject an effective amount of a compound of claim 1 , such that said subject is treated.
15 . The method of claim 14 , wherein said tetracycline responsive state is a bacterial infection, a viral infection, or a parasitic infection.
16 . The method of claim 14 , wherein said compound is metabolized in vivo to a compound of the formula:
17 . A method for treating a tetracycline responsive state in a subject, comprising administering to said subject an effective amount of a compound of claim 9 , such that said subject is treated.
18 . The method of claim 17 , wherein said tetracycline responsive state is a bacterial infection, a viral infection, or a parasitic infection.
19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
20 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 9 and a pharmaceutically acceptable carrier.