Cognition Enhancing Compounds and Compositions, Methods of Making, and Methods of Treating

Abstract

The invention relates generally to muscarinic agonists, which are useful for stimulating muscarine receptors, and treating cognitive disorders. Included among the muscarinic agonists disclosed herein are oxadiazole derivatives, compositions, and preparations thereof. Methods of synthesizing oxadiazole compounds also are provided. This disclosure also relates in part to compositions for enhancing cognitive function in subjects such as humans, the compositions comprising a muscarinic agonist or a pharmaceutically suitable form thereof. This disclosure relates in part to methods of treating animals such as humans by administering such compositions.

1 . A compound of Formula XI, a stereoisomer thereof or a pharmaceutically acceptable salt of said compound or stereoisomer, wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         wherein 
         X is O or S; 
         R 1  is NH 2 , a C 1-6  alkyl group or a C 3-6  cycloalkyl group, wherein the alkyl or cycloalkyl groups are optionally substituted with 1 or more D; 
         R 2a , R 2b , R 4a , R 4b , R 5 , R 6a , and R 6b  are independently selected from H or D; and 
         R 3  is H, D or an amino-protecting group. 
       
     
     
         2 .- 13 . (canceled) 
     
     
         14 . A method of preparing a compound of Formula XI comprising contacting a compound of Formula XX 
       
         
           
           
               
               
           
         
         with N-hydroxyguanidine or R′—C(NOH)NH 2 , wherein R′ is a C 1-6  alkyl or a C 3-6  cycloalkyl group, optionally substituted with one or more D, in the presence of a suitable base to provide the compound of Formula XI, 
       
       
         
           
           
               
               
           
         
         wherein 
         X is O; 
         R is a C 1-4  alkyl or a benzyl group; 
         R 1  is a C 1-6  alkyl group or a C 3-6  cycloalkyl group, wherein the alkyl or cycloalkyl groups are optionally substituted with 1 or more D; 
         R 2a , R 2b , R 4a , R 4b , R 5 , R 6a , and R 6b  are independently selected from H or D; and 
         R 3  is a base-stable amino-protecting group. 
       
     
     
         15 .- 150 . (canceled)