Claims
- 1. A substituted tetracycline compound of Formula I:
- 2. The tetracycline compound of claim 1, wherein R4 and R4′ are hydrogen or the oxygen of a carbonyl group, X is CR6R6′; R2, R2′, R6, R6′, R8, R9, R10, R11, and R12 are each hydrogen; and R5 is hydroxy or hydrogen.
- 3. The tetracycline compound of claim 2, wherein R4, R4′, and R5 are each hydrogen.
- 4. The tetracycline compound of claim 3, wherein R7 is aryl.
- 5. The tetracycline compound of claim 4, wherein R7 is substituted or unsubstituted phenyl.
- 6. The tetracycline compound of claim 4, wherein said aryl group is substituted or unsubstituted napthyl.
- 7. The tetracycline compound of claim 4, wherein R7 is heteroaryl.
- 8. The tetracycline compound of claim 3, wherein R7 is substituted or unsubstituted alkyl.
- 9. The tetracycline compound of claim 3, wherein R7 is substituted or unsubstituted alkenyl.
- 10. The tetracycline compound of claim 3, wherein R7 is substituted or unsubstituted alkynyl.
- 11. The tetracycline compound of claim 3, wherein R7 is alkylcarbonyl amino.
- 12. The tetracycline compound of claim 3, wherein R7 is carbonyl.
- 13. The tetracycline compound of claim 3, wherein R7 is substituted or unsubstituted imino.
- 14. The tetracycline compound of claim 3, wherein R7 is NR7c(C═W′)WR7a.
- 15. The tetracycline compound of claim 3, wherein R7 is sulfonamido.
- 16. A tetracycline compound of the formula
- 17. A 7,9-substituted tetracycline compound of Formula III:
- 18. The tetracycline compound of claim 17, wherein X is CR6R6′; R2, R2′, R6, R6′, R8, R10, R11, and R12 are each hydrogen; R and R4′ are each hydrogen or the oxygen of a carbonyl group; and R5 is hydroxy or hydrogen.
- 19. The tetracycline compound of claim 18, wherein R4 and R4′ are each hydrogen and R5 is hydrogen.
- 20. The tetracycline compound of claim 19, wherein R7 is aryl.
- 21. The tetracycline compound of claim 20, wherein R7 is substituted or unsubstituted phenyl.
- 22. The tetracycline compound of claim 19, wherein R7 is substituted or unsubstituted alkyl.
- 23. The tetracycline compound of claim 19, wherein said R7 is acyl.
- 24. The tetracycline compound of claim 19, wherein R7 is substituted or unsubstituted alkynyl.
- 25. The tetracycline compound of any one of claims 17, 20, 22, 23 or 24, wherein R9 is substituted or unsubstituted aryl.
- 26. The tetracycline compound of any one of claims 17, 20, 22, 23 or 24, wherein R9 is substituted or unsubstituted alkyl.
- 27. The tetracycline compound of any one of claims 17, 20, 22, 23 or 24, wherein said R9 is acyl.
- 28. The tetracycline compound of claim 27, wherein R9 is acetyl.
- 29. The tetracycline compound of any one of claims 17, 20, 22, 23 or 24, wherein R9 is substituted or unsubstituted alkynyl.
- 30. A tetracycline compound of formula IV:
- 31. The tetracycline compound of claim 1, wherein R4 and R4′ are each hydrogen or the oxygen of a carbonyl group; X is CR6R6′; R2, R2′, R5, R6, R6′, R8, R9, R10, R11, and R12 are each hydrogen; R7 is NR7′R7″; R7′ and R7″ are each lower alkyl; and R4 and R4′ are each hydrogen.
- 32. The tetracycline compound of claim 31, wherein R9 is substituted or unsubstituted aryl.
- 33. The tetracycline compound of claim 31, wherein R9 is substituted or unsubstituted alkynyl.
- 34. The tetracycline compound of claim 31, wherein R9 is alkyl.
- 35. The tetracycline compound of claim 31, wherein R9 is —(CH2)0-3NR9cC(=Z′)ZR9a.
- 36. The tetracycline compound of claim 31, wherein R9 is —N═S.
- 37. The tetracycline compound of claim 31, wherein R9 is aminoalkyl.
- 38. The tetracycline compound of claim 37, wherein said aminoalkyl is alkylaminoalkyl.
- 39. The tetracycline compound of claim 31, wherein R9 is substituted or unsubstituted alkyl amino.
- 40. A tetracycline compound of the formula:
- 41. A tetracycline compound of the formula (VI):
- 42. The tetracycline compound of claim 41, wherein R4 and R4′ are each hydrogen.
- 43. The tetracycline compound of claim 42, wherein R6 is alkyl.
- 44. The tetracycline compound of claim 42, wherein R6 is aryl.
- 45. The tetracycline compound of claims 42, wherein R6 is an alkoxyphenyl group, a halophenyl group, a carboxyphenyl group, an acylphenyl group, a cyanophenyl group, a nitrophenyl group, a naphthyl group, a dialkylphenyl group, an alkylphenyl group; a t-butyl group; or an aminoalkanethio group.
- 46. A tetracycline compound of formula VII:
- 47. The compound of claim 46, wherein R4 and R4′ are hydrogen or the oxygen of a carbonyl group, X is CR6R6′; R2, R2′, R6, R6′, R10, R11, and R12 are each hydrogen; R5 is hydroxy or hydrogen; and R7 and R9 are each independently amino, dialkylamino, or hydrogen.
- 48. The compound of claim 47, wherein R4, R4′, and R5 are each hydrogen; R7is hydrogen; and R9 is hydrogen or amino.
- 49. The compound of claim 48, wherein R8 is halogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl.
- 50. A tetracycline compound of the formula (VIII):
- 51. The compound of claim 50, wherein said compound is 8-phenyl 4-dedimethylamino doxycycline, 8-bromo 4-dedimethylamino doxycycline, 8-(p-nitrophenyl) 4-dedimethylamino doxycycline, 8-ethynyl-9-amino 4-dedimethylamino doxycycline or 8-phenyl-9-amino 4-dedimethylamino doxycycline.
- 52. A tetracycline compound selected from the group consisting of:
- 53. A substituted tetracycline compound selected from the group listed in Table 2, and pharmaceutically acceptable esters, prodrugs, and salts thereof.
- 54. A method for treating a tetracycline responsive state in a subject, comprising administering to said subject a tetracycline compound of any one of claims 1, 16, 17, 30, 40, 41, 46, 52, or 53, such that said subject is treated.
- 55. The method of claim 54, wherein said tetracycline responsive state is not a bacterial infection.
- 56. The method of claim 54, wherein said subject is a human.
- 57. A pharmaceutical composition comprising a therapeutically effective amount of a tetracycline compound of any one of claims 1, 16, 17, 30, 40, 41, 46, 52, or 53, and a pharmaceutically acceptable carrier.
- 58. The tetracycline compound of any one of claims 1, 16, 17, 30, 40, 41, 46, 52, or 53, wherein said compound is non-antibacterial.
- 59. A method for modulating tetracycline efflux, comprising administering an effective amount of a tetracycline compound, such that tetracycline efflux is modulated, wherein said tetracycline compound is of any one of claims 1, 16, 17, 30, 40, 41, 46, 52, or 53.
RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application Serial No. 60/367,049, entitled “8-Substituted 4-Dedimethylamino Tetracycline Compounds,” filed Mar. 21, 2002; U.S. Provisional Patent Application Serial No. 60/346,930, entitled “7-Substituted 4-Dedimethylamino Tetracycline Compounds,” filed Jan. 8, 2002; U.S. Provisional Patent Application Serial No. 60/346,929, entitled “7, 9-Substituted 4-Dedimethylamino Tetracycline Compounds,” filed Jan. 8, 2002; U.S. Provisional Patent Application Serial No. 60/347,065, entitled “9-Substituted 4-Dedimethylamino Minocycline Compounds,” filed Jan. 8, 2002; and U.S. Provisional Patent Application Serial No. 60/346,956, entitled “13-Substituted 4-Dedimethylamino Methacycline Compounds,” filed Jan. 8, 2002. The entire contents of each of these applications are hereby incorporated herein by reference.
Provisional Applications (5)
|
Number |
Date |
Country |
|
60367049 |
Mar 2002 |
US |
|
60346930 |
Jan 2002 |
US |
|
60346929 |
Jan 2002 |
US |
|
60347065 |
Jan 2002 |
US |
|
60346956 |
Jan 2002 |
US |