Claims
- 1. A compound represented by the formula I:
- 2. A compound, prodrug, metabolite, salt, or solvate according to claim 1, wherein R11 is —(CH2)t(5 to 10 membered heterocyclic), —C(O)NR12R13, —(CH2)tNR12R13, —SO2NR12R13 or —CO2R12.
- 3. A compound of claim 2, wherein R11 is —(CH2)t(5 to 10 membered heterocyclic), —C(O)NR12R13, —SO2NR12R13 or —CO2R12.
- 4. A compound of claim 3, wherein R11 is —(CH2)t(5 to 10 membered heterocyclic) or —C(O)NR12R13.
- 5. A compound of claim 4, wherein R11 is —C(O)NR12R13, wherein R12 and R13 are independently selected from H, C1-C6 alkyl, C3-C10 cycloalkyl, —(CH2)t(C3-C10 cycloalkyl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9.
- 6. A compound of claim 5, wherein R11 is —C(O)NR12R13, and wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring is unsubstituted or substituted by 1 to 5 R5 substituents.
- 7. A compound of claim 6, wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring is unsubstituted or substituted with 1 to 5 R5 substituents.
- 8. A compound of claim 7, wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl ring, wherein said pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl ring is unsubstituted or substituted with 1 to 5 R5 substituents.
- 9. A compound of claim 8, wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl ring is unsubstituted or substituted with 1 to 5 R5 substituents.
- 10. A compound of claim 9, wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl ring, wherein said pyrrolidinyl is unsubstituted or substituted with 1 to 5 R5 substituents.
- 11. A compound of claim 10, wherein R12 and R13 are taken together with the nitrogen to which they are attached to form a pyrrolidin-1-yl ring, wherein said pyrrolidin-1-yl ring is unsubstituted or substituted with 1 to 5 R5 substituents.
- 12. A compound of claim 4, wherein R11 is a —(CH2)t(5 to 10 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R5 groups.
- 13. A compound of claim 12, wherein R11 is a —(CH2)t(5-8 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R5 groups.
- 14. A compound of claim 13, wherein R11 is a —(CH2)t(5 or 6 membered heterocyclic) group is unsubstituted or substituted with 1 to 5 R5 groups.
- 15. A compound of claim 14, wherein R11 is a —(CH2)t(5 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R5 groups.
- 16. A compound of claim 15, wherein R11 is a thiazolyl, unsubstituted or substituted by 1 to 5 R5 groups.
- 17. A compound of claim 15, wherein R11 is an imidazolyl, unsubstituted or substituted by 1 to 5 R5 groups.
- 18. A compound of claim 1, wherein R16 is a C1-C6 alkyl group.
- 19. A compound of claim 18, wherein R16 is methyl.
- 20. A compound of claim 1, wherein R14 is methyl.
- 21. A compound represented by the formula II:
- 22. A compound of claim 21, R16 is a C1-C6 alkyl group.
- 23. A compound of claim 22, R16 is methyl.
- 24. A compound of claim 21, wherein R14 is methyl.
- 25. A compound represented by the formula III:
- 26. A compound of claim 25, wherein R14 is methyl.
- 27. A compound represented by the formula IV:
- 28. A compound of claim 27, wherein R14 is methyl.
- 29. A compound of claim 1 wherein said compound is selected from the group consisting of:
- 30. A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 and a pharmaceutically acceptable carrier.
- 31. The pharmaceutical composition of claim 30, wherein said hyperproliferative disorder is cancer.
- 32. The pharmaceutical composition of claim 31, wherein said cancer is brain, lung, kidney, renal, ovarian, ophthalmic, squamous cell, bladder, gastric, pancreatic, breast, head, neck, oesophageal, gynecological, prostate, colorectal or thyroid cancer.
- 33. The pharmaceutical composition of claim 30, wherein said hyperproliferative disorder is noncancerous.
- 34. The pharmaceutical composition of claim 33, wherein said hyperproliferative disorder is a benign hyperplasia of the skin or prostate.
- 35. A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, enzymes, topoisomerase inhibitors, biological response modifiers, anti-hormones, and anti-androgens, and a pharmaceutically acceptable carrier.
- 36. A pharmaceutical composition for the treatment of pancreatitis or kidney disease in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 and a pharmaceutically acceptable carrier.
- 37. A pharmaceutical composition for the prevention of blastocyte implantation in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 and a pharmaceutically acceptable carrier.
- 38. A pharmaceutical composition for treating a disease related to vasculogenesis or angiogenesis in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 and a pharmaceutically acceptable carrier.
- 39. The pharmaceutical composition of claim 38 wherein said disease is selected from the group consisting of tumor angiogenesis, chronic inflammatory disease, atherosclerosis, skin diseases, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian, breast, lung, pancreatic, prostate, colon and epidermoid cancer.
- 40. A pharmaceutical composition for treating a disease related to vasculogenesis or angiogenesis in a mammal comprising a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1, a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of an antihypertensive agent, and a pharmaceutically acceptable carrier.
- 41. A method of treating a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1.
- 42. The method of claim 41 wherein said hyperproliferative disorder is cancer.
- 43. The method of claim 42 wherein said cancer is brain, lung, ophthalmic, squamous cell, renal, kidney, ovarian, bladder, gastric, pancreatic, breast, head, neck, oesophageal, prostate, colorectal, gynecological or thyroid cancer.
- 44. The method of claim 41 wherein said hyperproliferative disorder is noncancerous.
- 45. The method of claim 44 wherein said hyperproliferative disorder is a benign hyperplasia of the skin or prostate.
- 46. A method for the treatment of a hyperproliferative disorder in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, anti-hormones, and anti-androgens.
- 47. A method of treating pancreatitis or kidney disease in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1.
- 48. A method of preventing blastocyte implantation in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1.
- 49. A method for treating a disease related to vasculogenesis or angiogenesis in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1.
- 50. The method of claim 49 wherein said disease is selected from the group consisting of tumor angiogenesis, chronic inflammatory disease, atherosclerosis, skin diseases, diabetes, diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, hemangioma, glioma, melanoma, Kaposi's sarcoma and ovarian, breast, lung, pancreatic, prostate, colon and epidermoid cancer.
- 51. A method for treating a disease related to vasculogenesis or angiogenesis in a mammal comprising administering to said mammal a therapeutically effective amount of a compound, prodrug, metabolite, salt or solvate of claim 1 in conjunction with a therapeutically effective amount of an anti-hypertensive agent.
Parent Case Info
[0001] The present patent application claims priority to U.S. Serial No. 60/389,110, filed Jun. 14, 2002, which is hereby incorporated by reference in its entirety for all purposes.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60389110 |
Jun 2002 |
US |