Claims
- 1. A succinate or malonate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)- phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 2. The compound of claim 1, wherein the succinate complex is a monosuccinate, hemisuccinate or sesquisuccinate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)- phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 3. The compound of claim 2, wherein the succinate complex is a monosuccinate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 4. The compound of claim 2, wherein the succinate complex is a hemisuccinate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 5. The compound of claim 2, wherein the succinate complex is a sesquisuccinate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 6. A method of treating abnormal cell growth in a mammal comprising administering to said mammal an amount of a monosuccinate, hemisuccinate or sesquisuccinate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide that is effective in treating abnormal cell growth.
- 7. A method according to claim 6, wherein said abnormal cell growth is cancer.
- 8. The method according to claim 7 wherein said cancer is selected from lung cancer, non small cell lung (NSCL) cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, gastric cancer, colon cancer, breast cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), colorectal cancer (CRC), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, or a combination of one or more of the foregoing cancers.
- 9. The method according to claim 8, wherein said cancer is selected from breast cancer, colon cancer, ovarian cancer, non small cell lung (NSCL) cancer, colorectal cancer (CRC), prostate cancer, bladder cancer, renal cancer, gastric cancer, endometrial cancer, head and neck cancer, and esophagel cancer.
- 10. The method according to claim 9, wherein said cancer is selected from renal cancer, gastric cancer, colon cancer, breast cancer, and ovarian cancer.
- 11. The method according to claim 10, wherein said cancer is selected from colon cancer, breast cancer or ovarian cancer.
- 12. The method according to claim 11, wherein said cancer is breast cancer.
- 13. The method according to claim 11, wherein said cancer is ovarian cancer.
- 14. The method according to claim 11, wherein said cancer is colon cancer.
- 15. A method for the treatment of abnormal cell growth in a mammal which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, radiation, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxics, anti-hormones, and anti-androgens.
- 16. The method of claim 15, which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with a cytotoxic.
- 17. The method of claim 16, which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with Taxol®.
- 18. A method for the treatment of abnormal cell growth in a mammal which comprises administering to said mammal an amount of the compound of claim 1 that is effective in treating abnormal cell growth in combination with a compound selected from the group consisting of Cyclophosphamide, 5-Fluorouracil, Floxuridine, Gemcitabine, Vinblastine, Vincristine, Daunorubicin, Doxorubicin, Epirubicin, Tamoxifen, Methylprednisolone, Cisplatin, Carboplatin, CPT-11, gemcitabine, paclitaxel, and docetaxel.
- 19. The method of claim 18, comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with a compound selected from the group consisting Tamoxifen, Cisplatin, Carboplatin, paclitaxel and docetaxel.
- 20. A method for treating a mammal having a disease characterized by an overexpression of erbB2, comprising administering to the mammal the compound of claim 1 in an amount that is effective in treating a disease characterized by the overexpression of erbB2.
- 21. A method for treating a mammal having cancer characterized by an overexpression of erbB2, comprising administering to the mammal the compound of claim 2 in an amount that is effective in treating said cancer characterized by the overexpression of erbB2.
- 22. A method for inducing cell death comprising exposing a cell which overexpresses erbB2 to an effective amount of the compound of claim 1.
- 23. The method of claim 22, wherein the cell is a cancer cell.
- 24. The method of claim 23, wherein the cell is in a mammal.
- 25. The method of claim 24, wherein the mammal is a human.
- 26. The method of claim 22, further comprising exposing the cell to a growth inhibitory agent.
- 27. The method of claim 22, further comprising exposing the cell to a chemotherapeutic agent.
- 28. The method of claim 22, further comprising exposing the cell to radiation.
- 29. A method of treating cancer in a human, wherein the cancer expresses the erbB2 receptor, comprising administering to the human a therapeutically effective amount of the compound of claim 1 that has reduced affinity for the erbB1 receptor.
- 30. The method of claim 29, wherein the cancer is not characterized by overexpression of erbB1 receptor.
- 31. The method of claim 29, wherein the cancer is characterized by overexpression of the erbB1 and erbB2 receptor.
- 32. A pharmaceutical composition comprising an amount of a compound according to claim 1 effective to treat a hyperproliferative disorder in a mammal, and a pharmaceutically acceptable carrier.
- 33. The pharmaceutical composition of claim 32, wherein the composition is adapted for oral administration.
- 34. The pharmaceutical composition of claim 33, wherein the pharmaceutical composition is in tablet form.
- 35. The pharmaceutical composition of claim 33, wherein the pharmaceutical composition is in capsule form.
- 36. The compound of claim 1, wherein the malonate complex is a di-malonate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl}-allyl)-acetamide.
- 37. A method of treating abnormal cell growth in a mammal comprising administering to said mammal an amount of a di-malonate complex of E-2-Methoxy-N-(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)-phenylamino]-quinazolin-6-yl-allyl)-acetamide that is effective in treating abnormal cell growth.
- 38. A method according to claim 37, wherein said abnormal cell growth is cancer.
- 39. The method according to claim 38 wherein said cancer is selected from lung cancer, non small cell lung (NSCL) cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, gastric cancer, colon cancer, breast cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's Disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, prostate cancer, chronic or acute leukemia, lymphocytic lymphomas, cancer of the bladder, cancer of the kidney or ureter, renal cell carcinoma, carcinoma of the renal pelvis, neoplasms of the central nervous system (CNS), colorectal cancer (CRC), primary CNS lymphoma, spinal axis tumors, brain stem glioma, pituitary adenoma, or a combination of one or more of the foregoing cancers.
- 40. The method according to claim 39, wherein said cancer is selected from breast cancer, colon cancer, ovarian cancer, non small cell lung (NSCL) cancer, colorectal cancer (CRC), prostate cancer, bladder cancer, renal cancer, gastric cancer, endometrial cancer, head and neck cancer, and esophagel cancer.
- 41. The method according to claim 40, wherein said cancer is selected from renal cancer, gastric cancer, colon cancer, breast cancer, and ovarian cancer.
- 42. The method according to claim 41, wherein said cancer is selected from colon cancer, breast cancer or ovarian cancer.
- 43. The method according to claim 42, wherein said cancer is breast cancer.
- 44. The method according to claim 42, wherein said cancer is ovarian cancer.
- 45. The method according to claim 42, wherein said cancer is colon cancer.
- 46. A method for the treatment of abnormal cell growth in a mammal which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, radiation, cell cycle inhibitors, enzymes, topoisomerase inhibitors, biological response modifiers, antibodies, cytotoxics, anti-hormones, and anti-androgens.
- 47. The method of claim 46, which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with a cytotoxic.
- 48. The method of claim 47, which comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with Taxol®.
- 49. A method for the treatment of abnormal cell growth in a mammal which comprises administering to said mammal an amount of the compound of claim 1 that is effective in treating abnormal cell growth in combination with a compound selected from the group consisting of Cyclophosphamide, 5-Fluorouracil, Floxuridine, Gemcitabine, Vinblastine, Vincristine, Daunorubicin, Doxorubicin, Epirubicin, Tamoxifen, Methylprednisolone, Cisplatin, Carboplatin, CPT-11, gemcitabine, paclitaxel, and docetaxel.
- 50. The method of claim 49, comprises administering to said mammal an amount of a compound of claim 1 that is effective in treating abnormal cell growth in combination with a compound selected from the group consisting Tamoxifen, Cisplatin, Carboplatin, paclitaxel and docetaxel.
- 51. A method for treating a mammal having a disease characterized by an overexpression of erbB2, comprising administering to the mammal the compound of claim 2 in an amount that is effective in treating a disease characterized by the overexpression of erbB2.
- 52. A method for treating a mammal having cancer characterized by an overexpression of erbB2, comprising administering to the mammal the compound of claim 2 in an amount that is effective in treating said cancer characterized by the overexpression of erbB2.
- 53. A method for inducing cell death comprising exposing a cell which overexpresses erbB2 to an effective amount of the compound of claim 2.
- 54. The method of claim 53, wherein the cell is a cancer cell.
- 55. The method of claim 54, wherein the cell is in a mammal.
- 56. The method of claim 55, wherein the mammal is a human.
- 57. The method of claim 53, further comprising exposing the cell to a growth inhibitory agent.
- 58. The method of claim 53, further comprising exposing the cell to a chemotherapeutic agent.
- 59. The method of claim 53, further comprising exposing the cell to radiation.
- 60. A method of treating cancer in a human, wherein the cancer expresses the erbB2 receptor, comprising administering to the human a therapeutically effective amount of the compound of claim 36 that has reduced affinity for the erbB1 receptor.
- 61. The method of claim 60, wherein the cancer is not characterized by overexpression of erbB1 receptor.
- 62. The method of claim 60, wherein the cancer is characterized by overexpression of the erbB1 and erbB2 receptor.
- 63. A pharmaceutical composition comprising an amount of a compound according to claim 2 effective to treat a hyperproliferative disorder in a mammal, and a pharmaceutically acceptable carrier.
- 64. The pharmaceutical composition of claim 63, wherein the composition is adapted for oral administration.
- 65. The pharmaceutical composition of claim 64, wherein the pharmaceutical composition is in tablet form.
CONTINUING APPLICATION DATA
[0001] This invention claims the benefit of U.S. Provisional Application Serial No. 60/340,885, filed Dec. 12, 2001, the contents of the aforementioned patent applications are hereby incorporated by reference in their entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60340885 |
Dec 2001 |
US |