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.

That which is claimed is:  
     
         1 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       where X is carbon nitrogen bonded to a substituent species characterized as having a sigma m value greater than 0 or less than 0; X′ is nitrogen characterized as having a sigma m valve greater than 0 or less than 0; A, A′ and A″ individually are substituent species characterized as having a sigma m value greater than 0, less than 0 or 0; m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7, or 8; E I , E II , E III , E IV , E V  and E VI  individually represent hydrogen, lower alkyl or halo substituted lower alkyl, such that at least one of E I , E II , E III , E IV , E V  and E VI  is not hydrogen; Z′ and Z″ individually are hydrogen or lower alkyl; and the wavy line in the structure indicates that the compound can have a cis (Z) or trans (E) form.  
     
     
         2 . The method of  claim 1  whereby the compound has the trans (E) form.  
     
     
         3 . The compound of  claim 1  wherein A is hydrogen.  
     
     
         4 . The compound of  claim 1  wherein A, A′ and A″ are all hydrogen.  
     
     
         5 . The compound of  claim 1  wherein 1 or 2 of the substituents designated as E I , E II , E III , E IV , E V  and E VI  are non-hydrogen substituents.  
     
     
         6 . The compound of  claim 1  wherein m plus n is 2 or 3.  
     
     
         7 . The compound of  claim 1  wherein at least one of Z′ and Z″ are hydrogen.  
     
     
         8 . The compound of  claim 1  wherein Z′ is hydrogen and Z″ is methyl.  
     
     
         9 . The compound of  claim 1  selected from the group consisting of (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.  
     
     
         10 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       where X and X′ are individually nitrogen or carbon bonded to a substituent species characterized as having a sigma m value greater than 0, less than 0 or 0; A, A′ and A″ individually are substituent species characterized as having a sigma m value greater than 0, less than 0 or 0; m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7, or 8; E I , E II ,E III , E IV , E V  and E VI  individually represent hydrogen, lower alkyl or halo substituted lower alkyl, such that at least one of E I , E II , E III , E IV , E V  and E VI  is not hydrogen and with the proviso that E III , E IV , E V  and E VI  are selected to provide a chiral center having an S configuration; Z′ and Z″ individually are hydrogen or lower alkyl; and the wavy line in the structure indicates that the compound can have a cis (Z) or trans (E) form.  
     
     
         11 . A compound of the formula:  
       
         
           
           
               
               
           
         
       
       where X and X′ are individually nitrogen or carbon bonded to a substituent species characterized as having a sigma m value greater than 0, less than 0 or; A, A′ and A″ individually are substituent species characterized as having a sigma m value greater than 0, less than 0 or 0; m is an integer and n is an integer such that the sum of m plus n is 1, 2, 3, 4, 5, 6, 7, or 8; E I ,E II , E III , E IV , E V  and E VI  individually represent hydrogen, lower alkyl or halo substituted lower alkyl, such that at least one of E I , E II , E III , E IV , E V  and E VI  is not hydrogen and with the proviso that E III , E IV , E V  and E VI  are selected to provide a chiral center having a R configuration; Z′ and Z″ individually are hydrogen or lower alkyl; and the wavy line in the structure indicates that the compound can have a cis (Z) or trans (E) form.