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Claims for Patent: 8,618,141

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Claims for Patent: 8,618,141

Title:Aryl ureas with angiogenesis inhibiting activity
Abstract: 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.
Inventor(s): Dumas; Jacques (Bethany, CT), Scott; William J. (Guilford, CT), Elting; James (Madison, CT), Hatoum-Makdad; Holia (Hamden, CT)
Assignee: Bayer Healthcare LLC (Whippany, NJ)
Application Number:13/551,884
Patent Claims: 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-pyr- idyloxy)phenyl)urea of the formula below or a pharmaceutically acceptable salt thereof ##STR00012##

2. A method as in claim 1 wherein the compound N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyr- idyloxy)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-pyr- idyloxy)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-pyr- idyloxy)phenyl)urea of the formula below ##STR00013##

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-pyr- idyloxy)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-pyr- idyloxy)phenyl)urea of the formula below is between 0.01 to 200 mg/Kg of total body weight ##STR00014##
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