Heteroaromatic compounds as btk inhibitors

Abstract

The present invention encompasses compounds of the formula (I) wherein the groups R 1 , Cy and Y are defined herein, which are suitable for the treatment of diseases related to BTK, and processes for making these compounds, pharmaceutical preparations containing these compounds, and their methods of use.

1 - 23 . (canceled) 
     
     
         24 . A compound of the formula (I) 
       
         
           
           
               
               
           
         
       
       wherein:
 Cy is chosen from 
 
       
         
           
           
               
               
           
         
         each R 1  is independently chosen from hydrogen or methyl; 
         R 2  is L-Ar, wherein Ar is phenyl or pyridinyl and each is optionally substituted by one or more of halogen, halo C 1-4  alkyl, C 1-4  alkyl, C 1-4  alkoxy, —CN, halo C 1-4  alkoxy, or cycloalkyl; 
         L is —(CH 2 )— or —(CHCH 3 )—; 
         Y is C 6 -C 8  spirocycle containing 1 ring nitrogen atom, and is substituted by one R 3 ; 
         R 3  is chosen from 
       
       
         
           
           
               
               
           
         
       
       and
 each R 4  is independently chosen from hydrogen, C 1-4  alkyl, or C 3-4  cycloalkyl; 
 each group defined above for R 1 -R 4  and Y can be where possible partially or fully halogenated; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         25 . The compound according to  claim 24 , wherein
 Y is chosen from   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The compound according to  claim 24 , wherein Cy is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         27 . The compound according to  claim 24  and wherein Cy is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The compound according to  claim 24  chosen from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         32 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         33 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         34 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         35 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         41 . The compound according to  claim 28  of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         42 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 24  or a pharmaceutically acceptable salt thereof. 
     
     
         43 . A method of treating a disease chosen from rheumatoid arthritis, systemic lupus erythromatosis, lupus nephritis, Sjogren's disease, vasculitis, scleroderma, asthma, allergic rhinitis, allergic eczema, B cell lymphoma, multiple sclerosis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, graft versus host disease, psoriatic arthritis, ankylosing spondylitis and uveitis, comprising administering to a patient a therapeutically effective amount of a compound according to  claim 24  or a pharmaceutically acceptable salt thereof.