Crac channel inhibitors for the treatment of stroke and traumatic brain injury

Abstract

Described herein are methods of treatment of stroke and traumatic brain injury comprising administration of a CRAC channel inhibitor.

1 . A method for treating stroke or traumatic brain injury in an individual in need thereof comprising administering to the individual a therapeutically effective amount of a compound having the structure of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R″ 1  is 
       
       
         
           
           
               
               
           
         
         L 2  is —NH—C(═O)—, or —(═O)NH—; 
         R 2  is phenyl or pyridyl; wherein phenyl or pyridyl is optionally substituted with at least one R 3 ; 
         R 3  is independently selected from F, Cl, Br, I, —CN, —NO 2 , —OH, —OCF 3 , —OR 5 , and  13  N(R 5 ) 2 ; 
         n is an integer selected from 1-4; 
         each R 5  is independently selected from C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl; 
         R 7  is C 1 -C 6 alkyl; and 
         R 6  is selected from F, Cl, Br, I, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , —OR 5 , C 1 -C 6 alkyl, C 3 -Cscycloalkyl, and C1-C6haloalkyl; 
         or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof. 
       
     
     
         2 . The method of  claim 1  having the structure of Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 2  wherein L 2  is —NH—C(═O)—. 
     
     
         4 . The method of  claim 2  wherein R 2  is phenyl optionally substituted with at least one R 3 . 
     
     
         5 . The method of  claim 2  wherein R 2  is phenyl substituted with at least one R 3  selected from F, Cl, Br, I, —N, —OH, —OCF 3 , —OR 5 , and —N(R 5 ) 2 . 
     
     
         6 . The method of  claim 2  wherein R 6  is selected from —CF 3 , —OCF 3 , —OR 5 , C 1 -C 6 alkyl, and C 3 -C 8 cycloalkyl. 
     
     
         7 . The method of  claim 6  wherein R 6  is —CF 3  and R 7  is —CH 3 . 
     
     
         8 . The method of  claim 6  wherein R 6  is —CF 3  and R 7  is —CH 2 CH 3 . 
     
     
         9 . The method of  claim 2  wherein n is 1. 
     
     
         10 . The method of  claim 9  wherein R 3  is fluorine. 
     
     
         11 . The method of  claim 2  wherein R 2  is phenyl substituted with at least 2 F substituents. 
     
     
         12 . The method of  claim 2  wherein R 2  is phenyl substituted with at least 3 F substituents. 
     
     
         13 . The method of  claim 2  wherein R 2  is pyridyl. 
     
     
         14 . The method of  claim 13  wherein R 2  is pyridyl substituted with at least one R 3  selected from F, Cl, Br, —OH, —CN, —OCF 3 , —OR 5 , and —N(R 5 ) 2 . 
     
     
         15 . The method of  claim 14  wherein R 2  is pyridyl substituted with at least one fluorine. 
     
     
         16 .- 64 . (canceled)