Claims
- 1. A compound of the following structural formula 1
- 2. A compound of the following structural formula 2
- 3. A compound having the following structural formula 4
- 4. The compound of claim 1 wherein n is 0.
- 5. The compound of claim 1 wherein n is 1.
- 6. The compound of claim 1 wherein n is 2.
- 7. The compound of claim 1 wherein n is 3.
- 8. The compound of claim 1 wherein R is ethanoyl.
- 9. The compound of claim 1 wherein R1 is H, R2 is H, and R3 is H.
- 10. The compound of claim 1 wherein R4 is attached to ring carbon of (R)-configuration.
- 11. The compound of claim 1 wherein R4 is attached to ring carbon of (S)-configuration.
- 12. The compound of claim 1 wherein R4 is H, methyl, ethyl, phenyl, tert-butyl, n-propyl, or ethoxycarbonyl.
- 13. The compound of claim 1 wherein X is hydroxy, methoxy, primary amino, N-methylamino, N-ethylamino, N-(n-propyl)amino, or N-(methyl ethanoate-2-yl)amino.
- 14. A mixture of two or more compounds of claim 1.
- 15. The mixture of claim 14, and further comprising at least one pair of stereoisomers of one of the compounds in the mixture.
- 16. A mixture of stereoisomers of the compound of claim 1.
- 17. The mixture of stereoisomers of claim 16 wherein n is 0.
- 18. The mixture of stereoisomers of claim 16 wherein n is 1.
- 19. The mixture of stereoisomers of claim 16 wherein n is 2.
- 20. The mixture of stereoisomers of claim 16 wherein n is 3.
- 21. The mixture of stereoisomers of claim 16 wherein R is ethanoyl.
- 22. The mixture of stereoisomers of claim 16 wherein R1 is H, R2 is H, and R3 is H.
- 23. The mixture of stereoisomers of claim 16 wherein R4 is attached to ring carbon of (R)-configuration.
- 24. The mixture of stereoisomers of claim 16 wherein R4 is attached to ring carbon of (S)-configuration.
- 25. The mixture of stereoisomers of claim 16 wherein R4 is H, methyl, ethyl, phenyl, tert-butyl, n-propyl, or ethoxycarbonyl.
- 26. The mixture of stereoisomers of claim 16 wherein X is hydroxy, methoxy, primary amino, N-methylamino, N-ethylamino, N-(n-propyl)amino, or N-(methyl ethanoate-2-yl)amino.
- 27. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.
- 28. A pharmaceutical composition comprising the mixture of stereoisomers of claim 16 and a pharmaceutically acceptable carrier.
- 29. A method of treating, preventing, or inhibiting a disease or disorder associated with a bacterial infection, a protozoal infection, or cell proliferation in a subject which comprises administering to the subject a therapeutically effect amount of at least one compound of claim 1.
- 30. A method of treating, preventing, or inhibiting a disease or disorder associated with a bacterial infection, a protozoal infection, or cell proliferation in a subject which comprises administering to the subject a therapeutically effect amount of the mixture of stereoisomers of claim 16.
- 31. The method of claim 29, wherein the bacterial infection is caused by an organism belonging to Mycobacterium.
- 32. The method of claim 31, wherein the organism is Mycobacterium tuberculosis.
- 33. The method of claim 29, wherein the protozoal infection is caused by a Plasmodium parasite.
- 34. The method of claim 33, wherein the Plasmodium parasite is P. falciparum, P. vivax, P. ovale, or P. malariae.
- 35. The method of claim 29, wherein the disease or disorder associated with cell proliferation is cancer, papillomas, acute and chronic inflammation, rheumatoid arthritis, psoriasis, atherosclerosis, diabetic retinopathy, chronic obstructive pulmonary disorder, tuberculosis, chronic cholecystitis, osteoarthritis, rheumatic carditis, bronchiectasis, Hashimoto's thyroiditis, inflammatory bowel disease, or silicosis.
- 36. The method of claim 35, wherein the cancer is leukemia, CNS cancer, renal cancer, non-small cell lung cancer, melanoma, prostate cancer, colon cancer, ovarian cancer, or breast cancer.
- 37. The method of claim 30, wherein the bacterial infection is caused by an organism belonging to Mycobacterium.
- 38. The method of claim 37, wherein the organism is Mycobacterium tuberculosis.
- 39. The method of claim 30, wherein the protozoal infection is caused by a Plasmodium parasite.
- 40. The method of claim 39, wherein the Plasmodium parasite is P. falciparum, P. vivax, P. ovale, or P. malariae.
- 41. The method of claim 30, wherein the disease or disorder associated with cell proliferation is cancer, papillomas, acute and chronic inflammation, rheumatoid arthritis, psoriasis, atherosclerosis, diabetic retinopathy, chronic obstructive pulmonary disorder, tuberculosis, chronic cholecystitis, osteoarthritis, rheumatic carditis, bronchiectasis, Hashimoto's thyroiditis, inflammatory bowel disease, or silicosis.
- 42. The method of claim 41, wherein the cancer is leukemia, CNS cancer, renal cancer, non-small cell lung cancer, melanoma, prostate cancer, colon cancer, ovarian cancer, or breast cancer.
- 43. The method of claim 29, wherein the compound is an amide.
- 44. A method of inhibiting the growth of at least one Plasmodium parasite which comprises contacting the Plasmodium parasite with at least one compound of claim 1.
- 45. The method of claim 44, wherein the Plasmodium parasite is P. falciparum, P. vivax, P. ovale, or P. malariae.
- 46. The method of claim 45, wherein the Plasmodium parasite is resistant to an antimalarial drug.
- 47. A method for making the compound of claim 1 which comprises reacting a compound having the following structural formula 2
- 48. The method of claim 47, wherein the solvent is toluene, benzene, ether, THF, CH3CN, CH2Cl2, or mixtures thereof.
- 49. The method of claim 47, wherein the solvent is CH2Cl2.
- 50. The method of claim 47, wherein the reaction is conducted at a temperature range of about −35° C. to about 10° C. for about 3 to about 240 minutes.
- 51. The method of claim 47, wherein the reaction is conducted at a temperature of about 0° C. for about 15 minutes.
- 52. The method of claim 47, wherein a catalyst is used.
- 53. The method of claim 52, wherein the catalyst is sulfuric acid dissolved in CH3CN.
- 54. A method for making the compound of claim 1 which comprises reacting compound having the following structural formula 4
- 55. The method of claim 54, wherein the solvent is toluene, benzene, ether, THF, CH3CN, CH2Cl2, or mixtures thereof.
- 56. The method of claim 54, wherein the solvent is CH2Cl2.
- 57. The method of claim 54, wherein the reaction is conducted at a temperature range of about −35° C. to about 10° C. for about 3 to about 240 minutes.
- 58. The method of claim 54, wherein the reaction is conducted at a temperature of about 0° C. for about 15 minutes.
- 59. The method of claim 54, wherein a catalyst is used.
- 60. The method of claim 59, wherein the catalyst is sulfuric acid dissolved in CH3CN.
- 61. A method for making the compound of claim 1 which comprises reacting the compound of claim 1 with LiOH, NaOH, or KOH in a solvent mixture of CH2Cl2— MeOH, or CH2Cl2— EtOH at about 20 to about 25° C., or in a solvent mixture of i-PrOH—H2O (1-9: 9-1, v/v) at about 79° C. for for about 10 to about 60 minutes, cooling to room temperature, diluting with water and a non-reacting organic solvent, and water layer acidifying to pH 2 with diluted HCl.
- 62. The method of claim 61, wherein the non-reacting organic solvent is CH2Cl2.
- 63. A method for making the compound of claim 1 which comprises reacting the acid of the compound of claim 1 with ClCO2Et in the presence of an organic base and then adding ammonia, primary amine, secondary amine, or an ammonium salts thereof and tertiary base.
- 64. The method of claim 63, wherein the organic base is Et3N, in CH2Cl2.
- 65. A method for making the compound of claim 2 which comprises reacting a compound having the structural formula 5
- 66. A method for making the compound of claim 3 which comprises reacting a compound having the structural formula 3
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Patent Application No. 60/356,633 filed Feb. 9, 2002, which names Bogdan A. Solaja, Gabriella Pocsfalvi, Dennis E. Kyle, Dej an Opsenica, and Wilbur K. Milhous as joint inventors and is herein incorporated by reference in its entirety.
ACKNOWLEDGMENT OF GOVERNMENT SUPPORT
[0002] This invention was made by employees of the United States Army. The government has rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60356633 |
Feb 2002 |
US |