Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use

Abstract

Indazole compounds that modulate and/or inhibit the ophthalmic diseases and the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating ophthalmic diseases and cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

1 - 2 . (canceled)  
     
     
         3 . A method of treating age related macular degeneration, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         4 . A method of treating choroidal neovascularization, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         5 . A method of treating retinopathies comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5  wherein the retinopathies comprise diabetic retinopathy and vitreoretinopathy, and retinopathy of prematurity.  
     
     
         7 . A method of treating retinitis comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         8 . The method of  claim 7  wherein the retinitis comprises cytomegalovirus retinitis.  
     
     
         9 . A method of treating uveitis, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 . A method of treating macular edema, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         11 . A method of treating glaucoma comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptablesolvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         12 . (canceled)  
     
     
         13 . A method of treating a mammalian disease condition mediated by protein kinase activity, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . A method according to  claim 13 , wherein the mammalian disease condition is associated with tumor growth, cell proliferation, or angiogenesis.  
     
     
         15 . A method of modulating the activity of a protein kinase receptor, comprising contacting the kinase receptor with an effective amount of a compound, pharmaceutically acceptable solvate, or pharmaceutically acceptable salt, selected from the croup consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         16 . A method according to  claim 15 , wherein the protein kinase receptor is a VEGF receptor.  
     
     
         17 - 30 . (canceled)