Aryl ureas with angiogenisis inhibiting activity
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.
1. A method for treating a condition in a human and/or other mammal which is ischemic retinal-vein occlusion or age related macular degeneration, comprising administering to a human or other mammal in need thereof an effective amount of
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 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 patient in need thereof in the same formulation or in separate formulations.
3. A method for treating age related macular degeneration comprising administering to a human or other mammal in need thereof an effective amount of 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
4. A method as in claim 1 wherein the disease that is treated is ischemic retinal-vein occlusion or age related macular degeneration,
in combination with an infectious disease selected from the group consisting of:
tuberculosis, Helicobacter pylori infection during peptic ulcer disease, Chaga's disease resulting from Trypanosoma cruzi infection, effects of Shiga-like toxin resulting from E. coli infection, effects of enterotoxin A resulting from Staphylococcus infection, meningococcal infection, and infections from Borrelia burgdorferi, Treponema pallidum , cytomegalovirus, influenza virus, Theiler's encephalomyelitis virus, and the human immunodeficiency virus (HIV).
5. A method as in claim 3 comprising administering the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea tosylate.
6. A method as in claim 1 comprising administering the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea tosylate.
7. A method for treating ischemic retinal-vein occlusion comprising administering to a human or other mammal in need thereof an effective amount of 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
8. A method as in claim 7 comprising administering the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N′-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl) urea tosylate.