Compounds capable of activating cholinergic receptors

Abstract

Compounds incorporating aryl substituted olefinic amine are provided. Representative compounds are (4E)-N-methyl-5-(3-pyridyl)-4-penten-2-amine, (4E)-N-methyl-5-(5-pyrimidinyl)-4-penten-2-amine, (4E)-N-methyl-5-(5-methoxy-3-pyridyl)-4-penten-2-amine, (4E)-N-methyl-5-(6-amino-5-methyl-3-pyridyl)-4-penten-2-amine, (2R)-(4E)-N-methyl-5-(3-pyridyl)-4-penten-2-amine, (2R)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridyl)-4-penten-2-amine, (4E)-N-methyl-5-(5-bromo-3-pyridyl)-4-penten-2-amine, (4E)-N-methyl-5-(5-ethoxy-3-pyridyl)-4-penten-2-amine, (2S)-(4E)-N-methyl-5-(3-pyridyl)-4-penten-2-amine, (4E)-N-methyl-5-(5-isopropoxy-3-pyridyl)-4-penten-2-amine and (2S)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridyl)-4-penten-2-amine.

1 . A method for synthesizing a compound of the formula 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein
 each of A, A I , and A II  is H; 
 X is COR I ; 
 R I  is C 1-5  alkyl; 
 X I  is N; 
 m is 1; 
 n is 1; 
 each of E I , E II , E III , E IV , and E V  is H; 
 E VI  is C 1-5  alkyl; and 
 each of Z I  and Z II  individually is H or C 1-5  alkyl; 
 
     comprising coupling of a halo-substituted pyridine with an olefin containing a secondary alcohol functionality. 
   
   
       2 . The method of  claim 1 , wherein
 each of A, A I , and A II  is H;   X is COR I ;   R I  is isopropyl;   X I  is N;   m is 1;   n is 1;   each of E I , E II , E III , E IV , and E V  is H;   geometry about the depicted wavy line is E;   E VI  is methyl;   Z I  is H; and   Z II  is methyl.   
   
   
       3 . The method of  claim 2 , wherein the halo-substituted pyridine is 3-bromo-5-isopropoxypyridine. 
   
   
       4 . The method of  claim 3 , wherein the olefin containing a secondary alcohol functionality is 4-penten-2-ol. 
   
   
       5 . The method of  claim 4 , further comprising converting to a p-toluenesulfonate ester by treating with p-toluenesulfonyl chloride. 
   
   
       6 . The method of  claim 5 , further comprising treating with methylamine. 
   
   
       7 . The method of  claim 1 , wherein the olefin containing a secondary alcohol functionality is (2S)-(4E)-5-(5-isopropoxy-3-pyridyl)-4-penten-2-ol. 
   
   
       8 . A method for synthesizing a compound of formula 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein
 each of A, A I , and A II  is H; 
 X is COR I ; 
 R I  is C 1-5  alkyl; 
 X I  is N; 
 m is 1; 
 n is 1; 
 each of E I , E II , E III , E IV , and E V  is H; 
 E VI  is C 1-5  alkyl; and 
 each of Z I  and Z II  individually is H or C 1-5  alkyl; 
 
     comprising coupling of a halo-substituted pyridine with an olefin containing a protected amine functionality. 
   
   
       9 . The method of  claim 8 , wherein
 each of A, A I , and A II  is H;   X is COR I ;   R I  is isopropyl;   X I  is N;   m is 1;   n is 1;   each of E I , E II , E III , E IV , and E V  is H;   geometry about the depicted wavy line is E;   E VI  is methyl;   Z I  is H; and   Z II  is methyl.   
   
   
       10 . The method of  claim 9 , wherein the halo-substituted pyridine is 3-bromo-5-isopropoxypyridine. 
   
   
       11 . The method of  claim 10 , wherein the olefin containing a protected amine functionality is N-methyl-N-(tert-butoxycarbonyl)-4-penten-2-amine.