초록

This invention relates to methods of using aryl ureas to treat diseases mediated by the VEGF induced signal transduction pathway characterized by abnormal angiogenesis or hyperpermeability processes.

대표청구항 ▼

1. A method of blocking tumor angiogenesis in a human or other mammal comprising administering to a human or other mammal with a tumor of the breast, gastrointestinal tract, kidney, ovary or cervix, an effective amount of the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoy

1. A method of blocking tumor angiogenesis in a human or other mammal comprising administering to a human or other mammal with a tumor of the breast, gastrointestinal tract, kidney, ovary or cervix, an effective amount of the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea of the formula below or a pharmaceutically acceptable salt thereof 2. A method as in claim 1 wherein the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea or a pharmaceutically acceptable salt thereof is administered simultaneously with another angiogenesis inhibiting agent to a human or other mammal with a tumor of the breast, gastrointestinal tract, kidney, ovary or cervix in the same formulation or in separate formulations. 3. A method as in claim 1 wherein the tumor that is treated is characterized by abnormal angiogenesis or hyperpermiability processes, which are mediated by KDR (VEGFR-2). 4. A method as in claim 1 wherein the tumor that is treated is characterized by abnormal angiogenesis or hyperpermiability processes, which are not raf-mediated. 5. A method as in claim 4 wherein the tumor that is treated is characterized by abnormal angiogenesis or hyperpermiability processes, which are not p38-mediated. 6. A method of blocking tumor angiogenesis in a human or other mammal comprising administering to a human or other mammal with a tumor of the breast, gastrointestinal tract, kidney, ovary or cervix, an effective amount of the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea tosylate. 7. A method of blocking angiogenesis in a tumor of the kidney comprising administering to a human or other mammal with a tumor of the kidney an effective amount of the tosylate salt of N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea of the formula below 8. A method as in claim 7 wherein the tumor of the kidney that is treated is characterized by abnormal angiogenesis or hyperpermiability processes, which are not raf-mediated nor p38-mediated. 9. A method as in claim 8 wherein the tumor of the kidney that is treated is characterized by abnormal angiogenesis or hyperpermiability processes, which are mediated by KDR (VEGFR-2). 10. The method of claim 6, wherein the effective amount of the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea tosylate is between 0.01 to 200 mg/Kg of total body weight. 11. The method of claim 7, wherein the effective amount of the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea of the formula below is between 0.01 to 200 mg/Kg of total body weight