Claims
- 1. A compound according to formula (I) or a pharmaceutically acceptable salt thereof:
- 2. The compound of claim 1, wherein the optionally formed 4 to 7-membered ring between R2 and R3 is a 6-membered ring.
- 3. The compound of claim 1, wherein the optionally formed 4 to 7-membered ring between R4 and R5 is a 6-membered ring.
- 4. The compound of claim 1, wherein the compound is:
- 5. The compound of claim 1, wherein the compound is:
- 6. The compound of claim 1, wherein the compound is:
- 7. The compound of claim 1, wherein the compound is:
- 8. The compound of claim 1, wherein the compound is:
- 9. The compound of claim 1, wherein the compound is:
- 10. A compound of the formula:
- 11. A composition comprising a compound according to formula I, and a pharmaceutically acceptable carrier:
- 12. The composition of claim 11, wherein the optionally formed 4 to 7-membered ring between R2 and R3 is a 6-membered ring.
- 13. The composition of claim 11, wherein the optionally formed 4 to 7-membered ring between R4 and R5 is a 6-membered ring.
- 14. A composition comprising the compound
- 15. A composition comprising the compound
- 16. A composition comprising the compound
- 17. A composition comprising the compound
- 18. A composition comprising the compound
- 19. A composition comprising the compound
- 20. A composition comprising the compound
- 21. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment comprising administering a therapeutically effective amount of a composition comprising one or more non-toxic pharmaceutically acceptable carriers and a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
- 22. The method of claim 21, wherein the compound of formula (J) is selected from the group consisting of:
- 23. The method of claim 21, wherein the Mycobacterium is selected from the group consisting of Mycobacterium aviumn complex (MAC), Mycobacterium kansaii, Mycobacterium marinum, Mycobacterium phlei, Mycobacterium ulcerans, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium terrae complex, Mycobacterium haemophilum, Mycobacterium fortuitum, Mycobacterium tuberculosis, Mycobacterium laprae, Mycobacterium scrofulaceum and Mycobacterium smegmatis.
- 24. The method of claim 21, wherein the Mycobacterium is Mycobacterium tuberculosis.
- 25. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment wherein the Mycobacterium is selected from the group consisting of Mycobacterium avium complex (MAC), Mycobacterium kansaii, Mycobacterium marinum, Mycobacterium phlei, Mycobacterium ulcerans, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium terrae complex, Mycobacterium haemophilum, Mycobacterium fortuitum, Mycobacterium tuberculosis, Mycobacterium laprae, Mycobacterium scrofulaceum and Mycobacterium smegmatis, comprising administering to the mammal a compound according to any of claims 2-10, or a pharmaceutically acceptable salt thereof.
- 26. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment wherein the Mycobacterium is Mycobacterium tuberculosis, comprising administering to the mammal a compound according to any of claims 2-10, or a pharmaceutically acceptable salt thereof.
- 27. The method according to claim 21, further comprising the administration of anti-microbial agent, an antiviral compound, an immunostimulant, an immunomodulator, an antibiotic, a chemokine inhibitor, or a pharmaceutically acceptable salt thereof.
- 28. The method of claim 27, wherein the anti-microbial agent is an anti-mycobacterial agent.
- 29. The method of claim 28, wherein the anti-mycobacterial agent is an anti-TB agent.
- 30. The method of claim 29, wherein the anti-TB agent comprises isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide or ethambutol.
- 31. The method of claim 27, wherein the antiviral compound is a protease inhibitor.
- 32. The method of claim 31, wherein the protease inhibitor is selected from the group consisting of indinavir, saquinavir, ritonavir, and nelfinavir.
- 33. The method of claim 27, wherein the antiviral compound is a biflavanoid.
- 34. The method of claim 33, wherein the biflavanoid is selected from the group consisting of robustaflavone, amentoflavone, and a derivative or salt thereof.
- 35. The method of claim 27, wherein the antiviral compound is selected from the group consisting of AZT, ddC, ddI, D4T, 3TC, acyclovir, gancyclovir, fluorinated nucleosides and normucleoside analog compounds such as delavirdine and nevirapine, and efavirenz, α-interfon, recombinant CD4, amantadine, rimantadine, ribavirin, and vidarabine.
- 36. The method of claim 27, wherein the immunostimulant is an interleukin or cytokine.
- 37. The method of claim 27, wherein the antibiotic is an antibacterial agent, antifungal agent, or anti-pneumocysitis agent.
- 38. A method of treating a patient who has a disease or condition selected from the group consisting of tuberculosis, tuberculosis associated with immunosuppression, tuberculosis associated with an immunodeficiency, tuberculosis associated with infection by human immunodeficiency virus (HIV), and tuberculosis associated with acquired immune deficiency syndrome (AIDS) and who is in need of such treatment which includes administration of a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof:
- 39. The method of claim 38, wherein the compound of formula (I) is selected from the group consisting of:
- 40. A method of stepwise reductive amination comprising:
(a) contacting a compound comprising ketone moiety with an excess of a compound of the formula R′NH2, wherein R′ is selected from the group consisting of H, alkyl, alkenyl, alkynyl, and aryl under conditions that allow the ketone moiety to form an imine intermediate compound; and (b) contacting the intermediate compound of step (a) with an amount of a reducing agent sufficient to reduce the imine moiety of the intermediate compound to its amino analog, under conditions that allow reduction of the imine intermediate compound to its amino analog.
- 41. A method of stepwise reductive amination to prepare a compound of formula (I) wherein R6 is NH2 comprising:
(a) contacting a compound of formula (I), wherein R6 is ═O, with an excess of a compound of the formula R′NH2, wherein R′ is selected from the group consisting of H, alkyl, alkenyl, and alkynyl, under conditions that allow formation of an imine intermediate compound of formula (I), wherein R6 is ═NH; and (b) contacting the intermediate compound of step (a) with an amount of a reducing agent sufficient to reduce the imine moiety of the intermediate compound to its amino analog, under conditions that allow reduction of the imine intermediate compound to its amino analog.
- 42. The method of claim 41, wherein the compound of formula R′NH2 is NH3.
- 43. The method of claim 41, wherein the reducing agent is NaBH4.
- 44. The method of claim 41, wherein the compound of formula (I), wherein R6 is ═O, is added to a solution comprising the compound of formula R′NH2.
- 45. The method of claim 41, wherein the amount of reducing agent is from 0.1 to 50 molar equivalents with respect to the amount of imine intermediate.
- 46. The method of claim 41, wherein the amount of compound of formula R′NH2 is from 1 to 500 molar equivalents with respect to the amount of compound of formula (I), wherein R6 is ═O.
- 47. The method of claim 41, further comprising a metal additive in the step comprising reduction of the imine intermediate.
- 48. The method of claim 47, wherein the metal additive is selected from the group consisting of CeCl3, ZnCl2, AlCl3, TiCl4, SnCl3, and LnCl3.
- 49. The method of claim 41, wherein the method is performed at a temperature from about −78 to 120° C.
- 50. The method of claim 41, wherein the method is performed at a temperature of about room temperature.
- 51. A method of preparing a compound of formula (I) wherein R6 is ═NH or ═NR′ comprising:
(a) contacting a compound of formula (I), wherein R6 is ═O, with an excess of a compound of the formula R′NH2,
wherein R′ is selected from the group consisting of H, alkyl, alkenyl, and alkynyl, under conditions that allow formation of an imine or substitututed imine compound of formula (I), wherein R6 is ═NH or ═NR′.
- 52. A compound according to formula (I) or a pharmaceutically acceptable salt thereof.
- 53. A composition comprising the compound of claim 52 and a pharmaceutically acceptable carrier.
- 54. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment comprising administering a therapeutically effective amount a compound of claim 52 or a pharmaceutically acceptable salt thereof.
- 55. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment comprising administering a therapeutically effective amount of a composition comprising one or more non-toxic pharmaceutically acceptable carriers and a compound of claim 52 or a pharmaceutically acceptable salt thereof.
- 56. The method of claim 55, further comprising the administration of anti-microbial agent, an antiviral compound, an immunostimulant, an immunomodulator, an antibiotic, a chemokine inhibitor, or a pharmaceutically acceptable salt thereof.
- 57. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment comprising administering a therapeutically effective amount of the compound of claim 10 or a pharmaceutically acceptable salt thereof.
- 58. A method of treating infection or conditions related to infection by Mycobacterium in a mammal in need of such treatment comprising administering a therapeutically effective amount of a composition comprising one or more non-toxic pharmaceutically acceptable carriers and the compound of claim 10 or a pharmaceutically acceptable salt thereof.
- 59. The method of claim 58, further comprising the administration of anti-microbial agent, an antiviral compound, an immunostimulant, an immunomodulator, an antibiotic, a chemokine inhibitor, or a pharmaceutically acceptable salt thereof.
- 60. A method of treating a patient who has a disease or condition selected from the group consisting of tuberculosis, tuberculosis associated with immunosuppression, tuberculosis associated with an immunodeficiency, tuberculosis associated with infection by human immunodeficiency virus (HIV), and tuberculosis associated with acquired immune deficiency syndrome (AIDS) and who is in need of such treatment which includes administration of a therapeutically effective amount of a compound of claim 10 or a pharmaceutically acceptable salt thereof.
PRIORITY DATA AND GOVERNMENTAL RIGHTS
[0001] This application claims priority to U.S. Provisional application serial No. 60/276,531, filed Mar. 16, 2001. This work was supported in part by the National Institutes of Health (NIH) through SBIR Grant (#1 R43 AI49053-01). Accordingly, the United States government may have certain rights to the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60276531 |
Mar 2001 |
US |