Compounds and methods for kinase modulation, and indications therefor

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

That which is claimed is: 
     
         1 . A method of treating a patient diagnosed with metastatic melanoma comprising:
 (a) identifying a metastatic melanoma patient who is positive for a  V600E BRAF mutation; and   (b) administering to the patient identified in step (a) an effective amount of a sulfonamide compound or a pharmaceutically acceptable salt thereof, whose chemical structure comprises a Core Moiety I, as shown below:   
       
         
           
           
               
               
           
         
         in which R 112  is amino, substituted amino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or lower alkyl; 
         R 83  is hydrogen, fluoro, or chloro; and 
       
       
         
           
           
               
               
           
         
         represents a carbon-carbon bond connecting the Core Moiety I with the remainder of the compound, which comprises a hydrocarbon having 8-18 carbon atoms and one or more heteroatoms. 
       
     
     
         2 . The method of  claim 1  in which R 112  is a substituted aryl. 
     
     
         3 . The method of  claim 2  in which the substituted aryl is a fluorobenzene radical. 
     
     
         4 . The method of  claim 2  in which the substituted aryl is a difluorobenzene radical. 
     
     
         5 . The method of  claim 2  in which R 83  is hydrogen. 
     
     
         6 . The method of  claim 1  in which R 112  is a lower alkyl. 
     
     
         7 . The method of  claim 1  in which the lower alkyl is n-propyl. 
     
     
         8 . The method of  claim 7  in which R 83  is fluoro. 
     
     
         9 . The method of  claim 1  in which R 112  is a difluorobenzene radical and R 83  is hydrogen. 
     
     
         10 . The method of  claim 1  in which the remainder of the compound includes a heteroaryl moiety. 
     
     
         11 . The method of  claim 10  in which the heteroaryl moiety includes two nitrogen atoms. 
     
     
         12 . The method of  claim 1  in which the patient's cancer has metastasized to the patient's brain.