IMIDAZO[1,2-b]PYRIDAZINE-BASED COMPOUNDS, COMPOSITIONS COMPRISING THEM, AND METHODS OF THEIR USE

Abstract

Imidazo[1,2-b]pyridazine-based compounds of the formula: are disclosed, wherein R 1 , R 2 and R 3 are defined herein. Compositions comprising the compounds and methods of their use to treat, manage and/or prevent diseases and disorders mediated by mediated by adaptor associated kinase 1 activity are also disclosed.

1 - 41 . (canceled) 
     
     
         42 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 X is or N; 
 each R 1A  is independently —OR 1C , —N(R 1C ) 2 , —C(O)R 1C , —C(O)OR 1C , —C(O)N(R 1C ) 2 , —N(R 1C )C(O)OR 1C , cyano, halo, or optionally substituted C 1-12  hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more R 1B ; 
 each R 1B  is independently —OR 1C , —N(R 1C ) 2 , —C(O)R 1C , —C(O)OR 1C , —C(O)N(R 1C ) 2 , —N(R 1C )C(O)OR 1C , cyano or halo; 
 each R 1C  is independently hydrogen or optionally substituted C 1-12  hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more of cyano, halo or hydroxyl; 
 each R 2C  is independently —OR 2D , —N(R 2D ) 2 , —C(O)R 2D , —C(O)OR 2D , —C(O)N(R 2D ) 2 , —N(R 2D )C(O)OR 2D , cyano, halo, or optionally substituted C 1-12  hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more with one or more amino, cyano, halo, hydroxyl, or R 2D ; 
 each R 2D  is independently hydrogen or optionally substituted C 1-12  hydrocarbyl or 2-12-membered heterocarbyl, which optional substitution is with one or more of amino, cyano, halo, or hydroxyl; and 
 m is 0-3. 
 
     
     
         43 . The compound of  claim 42 , with the provision that R 2C  is not optionally substituted phenyl or pyridinyl. 
     
     
         44 . The compound of  claim 42 , which is of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         45 . The compound of  claim 44 , which is of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The compound of  claim 45 , which is of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         47 . The compound of  claim 45 , which is of the formula: 
       
         
           
           
               
               
           
         
       
     
     
         48 - 66 . (canceled) 
     
     
         67 . The compound of  claim 42 , wherein each R 2D  is independently hydrogen or C 1-12  hydrocarbyl. 
     
     
         68 . The compound of  claim 67 , wherein at least one R 2D  is optionally substituted C 1-12  hydrocarbyl, which optional substitution is with one or more of amino, cyano, halo, hydroxyl. 
     
     
         69 . The compound of  claim 67 , wherein R 2D  is 2-12-membered heterocarbyl comprising at least one nitrogen atom. 
     
     
         70 . A pharmaceutical composition comprising a compound of  claim 42  and a pharmaceutically acceptable excipient or diluent.