3-(Arylamino)methylene-1, 3-dihydro-2H-indol-2-ones as kinase inhibitors

Abstract

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation.

1 . A method for treating diseases related to unregulated tyrosine kinase signal transduction, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound selected from the group consisting of 
 3-[(3-Bromo-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-[(4-Bromo-phenylamino)-methyl]-1,3-dihydro-indol-2-one,    3-[(3-Bromo-phenylamino)-methyl]-1,3-dihydro-indol-2-one,    3-[(4-Ethyl-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-Ethyl-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    4-[(2-Oxo-1,3-dihydro-indol-3-ylididenemethyl)-amino]-benzoic acid ethyl ester,    3-[(2-Ethyl-phenylamino)-methylene})-1,3-dihydro-indol-2-one,    3-[(3-Fluoro-4-methyl-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-[(3-Fluoro-2-methyl-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-[(4-Hydroxy-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-[(3-Chloro-4-hydroxy-phenylamino)-methylene]-1,3-dihydro-indol-2-one,    3-[(4-Fluoro-2-methyl-phenylamino)-methylene]-1,3-dihydro-indol-2-one and    pharmaceutically acceptable salts thereof.    
     
     
         2 . The method of  claim 1  wherein said disease is selected from the group consisting of cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders and metabolic diseases.  
     
     
         3 . The method of  claim 1  wherein said disease is a blood vessel proliferative disorder and the blood vessel proliferative disorder is selected from the group consisting of diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, arthritis and restenosis.  
     
     
         4 . The method of  claim 1  wherein said disease is a blood vessel proliferative disorder and the fibrotic disorder is selected from the group consisting of hepatic cirrhosis, atherosclerosis and surgical adhesions.  
     
     
         5 . The method of  claim 1  wherein said disease is a mesangial cell proliferative disorder and the mesangial cell proliferative disorder is selected from the group consisting of glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy syndromes, transplant rejection and glomerulopathies.  
     
     
         6 . The method of  claim 1  wherein said disease is a metabolic disorder and the metabolic disorder is selected from the group consisting of psoriasis, diabetes mellitus, wound healing, inflammation and neurodegenerative diseases.  
     
     
         7 . The method of  claim 2  wherein said blood vessel proliferative disorder is diabetic retinopathy.  
     
     
         8 . The method of  claim 2  wherein said blood vessel proliferative disorder is age-related macular degeneration.  
     
     
         9 . The method of  claim 6  wherein said metabolic disorder is psoriasis.