Claims
- 1. Compounds of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; —(CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, —CH2OCH2CH3, or —CH2SCH2CH3.
- 2. Compounds of Formula II: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; —(CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, —CH2OCH2CH3, or —CH2SCH2CH3.
- 3. The compounds of claims 1 or 2 wherein:R1 is an alkyl of 1-4 carbons, substituted with —OH or —OR4 where R4 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; R2 is H; and R3 is alkyl of 1-4 carbons, substituted with —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; and R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed.
- 4. The compounds of claims 1 or 2 wherein:R1 is —CH2CH2CH2OH or —CH2CH2CH2OCOCH2N(CH3)2; R2 is H; and R3 is —CH2OR7 wherein R7 is alkyl of 1-4 carbons.
- 5. The compounds of claims 1 or 2 represented in Table I:TABLE ICmpdR1R2R3 2CH2CH2CH2OHHCH2OCH3 3CH2CH2CH2OHHCH2OCH(CH3)2 4CH2CH2CH2OHHCH2OCH(CH3)CH2CH3 5CH2CH2CH2OHH(S)-CH2OCH(CH3)CH2CH3 6CH2CH2CH2OHH®-CH2OCH(CH3)CH2CH3 7CH2CHOHCH3HCH2OCH2CH3 8CH2CH2CH2OHHCH2OCH2CH2CH3 9CH2CH2CH2OHHCH2OCH2CH2CH2CH310CH2CH2CH2OHHCH(CH3)OCH2CH311CH2CH2CH2OHH(chiral) CH(CH3)OCH2CH312CH2CH2CH2OHH(chiral) CH(CH3)OCH2CH313CH2CH2CH2OHHCH(CH3)OCH314HCH2CHOHCH3CH2OCH2CH315CH2CH2CH2OHHCH(CH3)OCH2CH2CH2CH316CH2CH2CH2OHHCH(CH3)OCH(CH3)217CH2CH2CH2OHHCH2OC(CH3)318CH2CH2CH2OCOCH2NH2HCH2OCH(CH3)219CH2CH2CH2OCOCH(NH2)CH2—HCH2OCH(CH3)2CH2CH2CH2NH220CH2CH2CH2OCOCH2CH2NH2HCH2OCH(CH3)221CH2CH2CH2OCOCH2CH2—HCH2OCH(CH3)2CH2N(CH3)222CH2CH2CH2OCOCH2N(CH3)2HCH2OCH(CH3)223CH2CH2CH2OCOCH2CH2CH2—HCH2OCH(CH3)2CH2CH2NH224CH2CH2OHHCH2SCH2CH325CH2CH2CH2OHHCH2SCH2CH326CH2CH2CH2OHHCH2S(O)CH(CH3)228CH2CH2OHHCH2OH30HHCH2OH31HHCH2OCH2CH332HHCH2OCH(CH3)233CH2CH2CH2OHHCH(OH)CH334CH2CH2CH2OHHCH(OH)CH2CH335HHCH(OH)CH336HH(+/−) CH(OCH3)CH340CH2CH2CH2OHCH2OHCH2OCH(CH3)2
- 6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient or carrier.
- 7. A method for treating prostate disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5, —(CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1—4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, alkyl of 1-8 carbons substituted with —OH or —SR6, wherein R6 is alkyl of 1-4 carbons; —(CH2)nSR5, wherein n is 1 and R5 is alkyl of 1-4 carbons; or —CH2SR5, wherein R5 is alkyl of 1-4 carbons.
- 8. The method of claim 7 wherein the prostate disorder is prostate cancer or benign prostate hyperplasia.
- 9. A method for treating angiogenic disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; —(CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, alkyl of 1-8 carbons substituted with —OH or —SR6, wherein R6 is alkyl of 1-4 carbons; —(CH2)nSR5, wherein n is 1 and R5 is alkyl of 1-4 carbons; or —CH2SR5, wherein R5 is alkyl of 1-4 carbons.
- 10. The method of claim 9 wherein the angiogenic disorder is cancer of solid tumors, ocular disorders, macular degeneration, endometriosis, diabetic retinopathy, psoriasis, or hemangioblastoma.
- 11. A method for treating pathological disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; —(CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, alkyl of 1-8 carbons substituted with —OH or —SR6, wherein R6 is alkyl of 1-4 carbons; —(CH2)nSR5, wherein n is 1 and R5 is alkyl of 1-4 carbons; or —CH2SR5, wherein R5 is alkyl of 1-4 carbons.
- 12. The method of claim 11 wherein the pathological disorder is neoplasia, rheumatoid arthritis, chronic arthritis, pulmonary fibrosis, myelofibrosis, abnormal wound healing, atherosclerosis, or restenosis.
- 13. A method for treating neurodegenerative diseases and disorders, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, stroke, ischaemia, Huntington's disease, AIDS dementia, epilepsy, multiple sclerosis, peripheral neuropathy, chemotherapy induced peripheral neuropathy, AID related peripheral neuropathy or injuries of the brain or spinal chord which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; —(CH2)nS(O)yR5; CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, alkyl of 1-8 carbons substituted with —OH or —SR6, wherein R6 is alkyl of 1-4 carbons; —(CH2)nSR5, wherein n is 1 and R5 is alkyl of 1-4 carbons; or —CH2SR5, wherein R5 is alkyl of 1-4 carbons.
- 14. A method for treating multiple myeloma and leukemias which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of Formula I: wherein:R1 and R2 are the same or different and are independently selected from H, or alkyl of 1-8 carbons, substituted with —OH, or —OR4 where R4 is an alkyl of 1-4 carbons, aryl or the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; and R3 is —CH2OH; —CH2OR7; —(CH2)nSR5; (CH2)nS(O)yR5; —CH2SR5; or alkyl of 1-8 carbons substituted with —OH, —OR5, —OR8, —CH2OR7, —S(O)yR6 or —SR6; and wherein R5 is alkyl of 1-4 carbons or aryl; R6 is H, alkyl of 1-4 carbons or aryl of 6-10 carbons; R7 is H or alkyl of 1-4 carbons; R8 is the residue of an amino acid after the hydroxyl group of the carboxyl group is removed; n is an integer of 1-4; and y is 1 or 2; with the proviso that when R1 is (CH2)3OH and R2 is H, then R3 cannot be —CH2OH, alkyl of 1-8 carbons substituted with —OH or —SR6, wherein R6 is alkyl of 1-4 carbons; —(CH2)nSR5, wherein n is 1 and R5 is alkyl of 1-4 carbons; or —CH2SR5, wherein R5 is alkyl of 1-4 carbons.
- 15. The method of claim 14 wherein the leukemia is acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, or chronic lymphocytic leukemia.
- 16. The compound of claim 2 wherein R1 is (CH2)3OH, R2 is H, and R3 is CH2OCH(CH3)2.
- 17. The compound of claim 2 wherein R1 is (CH2)3OCOCH2N(CH3)2, R2 is H, and R3 CH2OCH(CH3)2.
- 18. A pharmaceutical composition comprising a compound of claim 16 and a pharmaceutically acceptable excipient or carrier.
- 19. A pharmaceutical composition comprising a compound of claim 17 and a pharmaceutically acceptable excipient or carrier.
- 20. A method for treating prostate disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 16.
- 21. A method for treating prostate disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 17.
- 22. The method of claim 20 wherein the prostate disorder is prostate cancer or benign prostate hyperplasia.
- 23. The method of claim 21 wherein the prostate disorder is prostate cancer or benign prostate hyperplasia.
- 24. A method for treating angiogenic disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 16.
- 25. A method for treating angiogenic disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 17.
- 26. The method of claim 24 wherein the angiogenic disorder is cancer of solid tumors, ocular disorders, macular degeneration, endometriosis, diabetic retinopathy, psoriasis, or hemangioblastoma.
- 27. The method of claim 25 wherein the angiogenic disorder is cancer of solid tumors, ocular disorders, macular degeneration, endometriosis, diabetic retinopathy, psoriasis, or hemangioblastoma.
- 28. A method for treating pathological disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 16.
- 29. A method for treating pathological disorders which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 17.
- 30. The method of claim 28 wherein the pathological disorder is neoplasia, rheumatoid arthritis, chronic arthritis, pulmonary fibrosis, myelofibrosis, abnormal wound healing, atherosclerosis, or restenosis.
- 31. The method of claim 29 wherein the pathological disorder is neoplasia, rheumatoid arthritis, chronic arthritis, pulmonary fibrosis, myelofibrosis, abnormal wound healing, atherosclerosis, or restenosis.
- 32. A method for treating neurodegenerative diseases and disorders, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, stroke, ischaemia, Huntington's disease, AIDS dementia, epilepsy, multiple sclerosis, peripheral neuropathy, chemotherapy induced peripheral neuropathy, AID related peripheral neuropathy or injuries of the brain or spinal chord which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 16.
- 33. A method for treating neurodegenerative diseases and disorders, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, stroke, ischaemia, Huntington's disease, AIDS dementia, epilepsy, multiple sclerosis, peripheral neuropathy, chemotherapy induced peripheral neuropathy, AID related peripheral neuropathy or injuries of the brain or spinal chord which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 17.
- 34. A method for creating multiple myeloma and leukemias which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 16.
- 35. A method for treating multiple myeloma and leukemias which comprises administering to a host in need of such treatment a therapeutically effective amount of a compound of claim 17.
- 36. The method of claim 34 wherein the leukemia is acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia or chronic lymphocytic leukemia.
- 37. The method of claim 35 wherein the leukemia is acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, or chronic lymphocytic leukemia.
Parent Case Info
This Application: claims benefit of U.S. Provisional Application Serial Nos. 60/227,803 filed Aug. 25, 2000 and 60/278,455 filed Mar. 23, 2001.
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