Substituted tetracycline compounds for treatment of
View Patent ↗Methods and compositions for the treatment of Bacillus anthracis infections are described.
1. A method for treating a bacillus anthracis infection in a subject, comprising administering to said subject an effective amount of a substituted tetracycline compound, such that said bacillus anthracis infection in said subject is treated, wherein said substituted tetracycline compound is of the formula I:
wherein
R 2″ is C(═O)—NR 2 R 2′ ;
R 2 , R 2′ , and R 3 are hydrogen;
R 4a and R 4b are each alkyl;
R 10 , R 11 , and R 12 are each hydrogen;
R 4 and R 4′ are each independently NR 4a R 4b or hydrogen;
R 5 and R 5′ are each hydrogen;
R 6 and R 6′ are each hydrogen;
R 7 is hydrogen, dialkylamino, alkyl, aryl, heterocyclic, or alkyl-O—N═C—CR 7g R 7h , wherein R 7g and R 7h are each independently hydrogen or alkyl;
R 8 is hydrogen;
R 9 is of the formula:
wherein:
J 5 and J 6 are each independently hydrogen, alkyl, alkenyl, or linked to form a ring; and
J 7 and J 8 are each alkyl, halogen, or hydrogen; and
X is CR 6′ R 6 ;
or a pharmaceutically acceptable salt, ester or enantiomer thereof.
2. The method of claim 1 , wherein R 7 is substituted or unsubstituted heteroaryl.
3. The method of claim 2 , wherein R 7 is substituted or unsubstituted pyrimidinyl, pyridinyl, or furanyl.
4. The method of claim 1 , wherein R 7 is hydrogen.
5. The method of claim 1 , wherein J 7 and J 8 are each hydrogen.
6. The method of claim 5 , wherein J 6 is hydrogen.
7. The method of claim 5 , wherein J 5 is substituted or unsubstituted alkyl.
8. The method of claim 7 , wherein J 5 is propyl.
9. The method of claim 5 , wherein J 5 and J 6 are linked to form a ring.
10. The method of claim 9 , wherein J 5 and J 6 are linked to form a substituted or unsubstituted piperidinyl ring or fused ring.
11. The method of claim 10 , wherein said fused ring is 2,3-dihydro-indole or decahydro-isoquinoline.
12. The method of claim 10 , wherein said piperidinyl ring is substituted with one or more halogens or one or more heterocyclic groups.
13. The method of claim 1 , wherein said substituted tetracycline compound is selected from the group consisting of:
14. The method of claim 1 , wherein said substituted tetracycline compound is administered in combination with a second agent.
15. The method of claim 14 , wherein said second agent is an antibiotic.
16. The method of claim 15 , wherein said second agent is selected from the group consisting of rifampin, vancomycin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin.
17. The method of claim 1 , wherein said bacillus anthracis is multidrug resistant.
18. The method of claim 1 , wherein R 7 is dimethylamino.
19. The method of claim 8 , wherein R 7 is substituted or unsubstituted heteroaryl, dimethylamino, or hydrogen.
20. The method of claim 9 , wherein R 7 is substituted or unsubstituted heteroaryl, dimethylamino, or hydrogen.
21. The method of claim 10 , wherein R 7 is substituted or unsubstituted heteroaryl, dimethylamino, or hydrogen.
22. The method of claim 11 , wherein R 7 is substituted or unsubstituted heteroaryl, dimethylamino, or hydrogen.
23. The method of claim 12 , wherein R 7 is substituted or unsubstituted heteroaryl, dimethylamino, or hydrogen.