Claims
- 1. A method of treating cancer comprising administering to a patient in need thereof an effective amount of a compound of Formula I:
- 2. The method of claim 1, wherein R1 is halo and p is 1.
- 3. The method of claim 1, wherein R1 is F or Cl and p is 1.
- 4. The method of claim 1, wherein Z is —NR3R4 wherein R3 and R4 are lower alkyl or form a morpholine ring.
- 5. The method of claim 1, wherein Z is:
- 6. The method of claim 1, wherein R2 is methyl and q is 2, wherein the methyls are bonded at the 3 and 5 positions.
- 7. The method of claim 1, wherein the compound of formula I is selected from the group consisting of
- 8. The method of claim 1, wherein the compound of formula I is selected from the group consisting of:
- 9. The method of claim 1, wherein the compound of Formula (I) is:
- 10. The method of claim 9, wherein the salt is a malate salt.
- 11. The method of claim 1, wherein the at least one chemotherapeutic agent is selected from the group consisting of taxanes, vinca alkyloids, topoisomerase I inhibitors and topoisomerase II inhibitors.
- 12. The method of claim 1, wherein the at least one chemotherapeutic agent is selected from the group consisting of paclitaxel, docetaxel, vinblastine, vincristine, vindesine, irinotecan, doxorubicin, epirubicin, leucovorin, etopside, teniposide, idarubicine, gemcitabine, daunorubicin, carboplatin, cisplatin, oxaliplatin, chlorambucil, melphalan, cyclophosphamide, ifosfamide, temozolomide, thiotepa, mitomycin C, busulfan, carmustine, lomustine, 5-fluorouracil, capecitabine, exemestane, methotrexate, trimetrexate, fluorouracil, fluorodeoxyuridine, azacytidine, mercaptopurine, thioguanine, pentostatin, cytarabine, fludarabine, hydroxyurea, bevacizumab, cetuximab, gefitinib and imatinib.
- 13. The method of claim 1, wherein the cancer is breast cancer, small cell lung carcinoma, colon cancer, non-small cell lung cancer, renal cell cancer, a gastrointestinal stromal tumor, thyroid cancer, a sarcoma or a neuroendocrine tumor.
- 14. The method of claim 1, wherein the cancer is non-small cell lung cancer and the at least one chemotherapeutic agent is carboplatin and paclitaxel.
- 15. The method of claim 1, wherein the cancer is non-small cell lung cancer and the at least one chemotherapeutic agent is carboplatin, taxotere, cisplatin, gemcitabine, 5-fluorouracil, irinotecan or leucovorin.
- 16. The method of claim 1, wherein the cancer is colon cancer and the at least one chemotherapeutic agent is 5-fluorouracil, oxaliplatin or leucovorin.
- 17. A method of treating cancer comprising administering to a patient in need thereof an effective amount of a compound selected from the group consisting of:
5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-diethylamino-ethyl)-amide; 5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-pyrrolidin-1-yl-ethyl)-amide; 5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-morpholin-4-yl-ethyl)-amide; (S)-5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-hydroxy-3-morpholin-4-yl-propyl)-amide; (R)-5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-hydroxy-3-morpholin-4-yl-propyl)-amide; 5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-hydroxy-3-morpholin-4-yl-propyl)-amide; 5-(5-Chloro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-hydroxy-3-morpholin-4-yl-propyl)-amide; 5-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid(2-ethylamino-ethyl)-amide; and 3-[3,5-dimethyl-4-(4-morpholin-4-yl-piperidine-1-carbonyl)-1H-pyrrol-2-methylene]-5-fluoro-1,3-dihydro-indol-2-one, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in combination with at least one chemotherapeutic agent selected from the group consisting of microtubule interference agents, topoisomerase inhibitors, alkylating agents, thymidylate synthase inhibitors, irreversible steroidal aromatase inactivators, anti-metabolites, pyrimidine antagonists, purine antagonists, ribonucleotide reductase inhibitors, and kinase inhibitors.
- 18. The method of claim 17, wherein the at least one chemotherapeutic agent is selected from the group consisting of taxanes, vinca alkyloids, topoisomerase I inhibitors and topoisomerase II inhibitors.
- 19. The method of claim 17, wherein the at least one chemotherapeutic agent is selected from the group consisting of paclitaxel, docetaxel, vinblastine, vincristine, vindesine, irinotecan, doxorubicin, epirubicin, leucovorin, etopside, teniposide, idarubicine, gemcitabine, daunorubicin, carboplatin, cisplatin, oxaliplatin, chlorambucil, melphalan, cyclophosphamide, ifosfamide, temozolomide, thiotepa, mitomycin C, busulfan, carmustine, lomustine, 5-fluorouracil, capecitabine, exemestane, methotrexate, trimetrexate, fluorouracil, fluorodeoxyuridine, azacytidine, mercaptopurine, thioguanine, pentostatin, cytarabine, fludarabine, hydroxyurea, bevacizumab, cetuximab, gefitinib and imatinib.
- 20. The method of claim 17, wherein the cancer is breast cancer, small cell lung carcinoma, colon cancer, non-small cell lung cancer, renal cell cancer, a gastrointestinal stromal tumor, thyroid cancer, a sarcoma or a neuroendocrine tumor.
RELATED APPLICATIONS
[0001] This application claims priority to provisional applications 60/426,386 filed Nov. 15, 2002, the entire content of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60426386 |
Nov 2002 |
US |