Butyrylcholinesterase inhibitors

Abstract

Butyrylcholinesterase inhibitors, their formulation, and their use primarily in the treatment of neurodegenerative diseases. These inhibitors generally are phosphates, phosphonates, phosphinates, and phosphoramidates. These inhibitors can be incorporated in pharmaceutical compositions and administered to a patient in therapeutically effective amounts to treat neurodegenerative diseases.

1 - 20 . (canceled) 
     
     
         21 . A compound of Formula 1: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         X is O or S; 
         Y is O or NH; 
         R 1  is n-butyl, isobutyl, cyclohexyl, n-pentyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 2  is n-butyl, isobutyl, cyclohexyl, n-pentyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 3  is methoxy, F, I, nitrile, carboxylic acid, or carbonyl; and 
         R 4  is methoxy, F, I, nitrile, carboxylic acid, or carbonyl. 
       
     
     
         22 . The compound of  claim 21 , wherein R 1  is n-butyl, isobutyl, cyclohexyl, n-pentyl, C 1-6  alkenyl, or phenyl substituted at least once, and each phenyl substituent is independently methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
     
     
         23 . The compound of  claim 21 , wherein the compound is a compound of Formula 7: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         R 1  is n-butyl, isobutyl, n-pentyl, phenyl or substituted phenyl; 
         R 2  is n-butyl, isobutyl, n-pentyl, phenyl or substituted phenyl; 
         R 3  is H, F, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; and 
         R 4  is H, F, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
       
     
     
         24 . A compound, wherein the compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         25 . A compound of Formula 2: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         X is O or S; 
         Y is O or NH; 
         R 1  is H, cyclohexyl, n-pentyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 2  is H, cyclohexyl, n-pentyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 3  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; 
         R 4  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; 
         R 5  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; and 
         R 6  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
       
     
     
         26 . The compound of  claim 25 , wherein the phenyl is substituted at least once, and each phenyl substituent is independently methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
     
     
         27 . A compound of Formula 3 or Formula 4: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         R 1  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 2  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 3  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; and 
         R 4  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
       
     
     
         28 . The compound of  claim 27 , wherein the phenyl is substituted at least once wherein each substituent is independently methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
     
     
         29 . The compound of  claim 27 , wherein C 1-6  alkyl is n-butyl, isobutyl, cyclohexyl, or n-pentyl. 
     
     
         30 . The compound of  claim 27 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         31 . A compound of Formula 5: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         R 1  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 2  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 3  is H, methyl, methoxy, F, Cl, Br, I, nitrile, carboxylic acid, or carbonyl; and 
         R 4  is H, methyl, methoxy, F, Cl, Br, I, nitrile, carboxylic acid, or carbonyl. 
       
     
     
         32 . The compound of  claim 31 , wherein the phenyl is substituted at least once, and each substituent is independently H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
     
     
         33 . The compound of  claim 31 , wherein C 1-6  alkyl is n-butyl, isobutyl, cyclohexyl, or n-pentyl. 
     
     
         34 . The compound of  claim 31 , wherein the compound is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         35 . A compound of Formula 6: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         R 1  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 2  is H, C 1-6  alkyl, C 1-6  alkenyl, phenyl or substituted phenyl; 
         R 3  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl; and 
         R 4  is H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
       
     
     
         36 . The compound of  claim 35 , wherein the phenyl is substituted at least once, and each substituent is independently H, methyl, methoxy, F, Cl, Br, I, NO 2 , nitrile, carboxylic acid, or carbonyl. 
     
     
         37 . The compound of  claim 35 , wherein C 1-6  alkyl is n-butyl, isobutyl, cyclohexyl, or n-pentyl.