Beta-amyloid pet imaging agents

Abstract

Novel derivatives of imidazopyridinylbenzeneamines and novel derivatives of benzothiazolylbenzeneamines are disclosed that offer improved behavior when used as imaging agents for positron emission tomography of beta-amyloids. Also disclosed is a palladium-catalyzed reaction scheme under microwave conditions for aryl thioethers in general that provides a high ratio of substitution relative to reduction and can be used for the imidazopyridinylbenzeneamine derivatives as well as other compounds of related structure.

1 - 10 . (canceled) 
     
     
         11 . A compound having the formula 
       
         
           
           
               
               
           
         
       
       wherein:
 R 11  is a member selected from the group consisting of C 1 -C 6  alkyl, aryl- or halo-substituted C 1 -C 6  alkyl, hydroxyl-substituted C 1 -C 6  alkyl, and carbamoyl C 1 -C 6 alkyl; 
 
       R 12  is a member selected from the group consisting of H, C 1 -C 6  alkyl, halo-substituted C 1 -C 6  alkyl, halo, and C 1 -C 6  alkylthio, and R 13  is a member selected from the group consisting of H and C 1 -C 3  alkyl, or R 12  and R 13  are joined to form a thio-C 1 -C 3  alkylene or alkylene linkage, and 
       R 14  is a member selected from the group consisting of H and C 1 -C 6  alkyl, and 
       X is CH or N. 
     
     
         12 . The compound of  claim 11  wherein R 11  is a member selected from the group consisting of C 1 -C 3  alkyl, fluoro-substituted C 1 -C 3  alkyl, hydroxyl-substituted C 1 -C 3  alkyl, and carbamoyl C 1 -C 3  alkyl. 
     
     
         13 . The compound of  claim 11  wherein R 11  is a member selected from the group consisting of methyl, ethyl, fluoromethyl, fluoroethyl, hydroxymethyl, hydroxyethyl, carbamoylmethyl, and carbamoylethyl. 
     
     
         14 . The compound of  claim 11  wherein R 12  is a member selected from the group consisting of H, C 1 -C 3  alkyl, chloro, bromo, chloro-substituted C 1 -C 3 alkyl, bromo-substituted C 1 -C 3  alkyl, and C 1 -C 3  alkylthio, and R   1 3  is a member selected from the group consisting of H and C 1 -C 3  alkyl, or R   1 2  and R   1 3  are joined to form a thiomethylene or alkylene linkage. 
     
     
         15 . The compound of  claim 11  wherein R 12  is a member selected from the group consisting of H, bromo, and methylthio, and R 13  is a member selected from the group consisting of H and methyl, or R 12  and R 13  are joined to form a thiomethylene or alkylene linkage. 
     
     
         16 . The compound of  claim 11  wherein R 14  is a member selected from the group consisting of H and methyl. 
     
     
         17 . The compound of  claim 11  wherein R 11  is a member selected from the group consisting of C 1 -C 3  alkyl, fluoro-substituted C 1 -C 3  alkyl, hydroxyl-substituted C 1 -C 3  alkyl, and carbamoyl C 1 -C 3  alkyl; R 12  is a member selected from the group consisting of H, C 1 -C 3  alkyl, chloro, bromo, chloro-substituted C 1 -C 3  alkyl, bromo-substituted C 1 -C 3  alkyl, and C 1 -C 3  alkylthio, and R   1 3  is a member selected from the group consisting of H and C 1 -C 3  alkyl, or R   1 2  and R   1 3  are joined to form a thiomethylene or alkylene linkage; and R 14  is a member selected from the group consisting of H and methyl. 
     
     
         18 . A method for imaging amyloid deposits in a patient, said method comprising administering to said patient a compound of  claim 11  and imaging portions of said patient where amyloid deposits occur when said patient is suffering from Alzheimer's disease. 
     
     
         19 . A method for imaging amyloid deposits in a patient, said method comprising administering to said patient a compound of  claim 11  and imaging portions of said patient where amyloid deposits occur when said patient is suffering from Alzheimer's disease.