Alpha2C adrenoreceptor agonists

Abstract

In its many embodiments, the present invention relates to a novel class of phenylmorpholine and phenylthiomorpholine compounds useful as α2C adrenergic receptor agonists, pharmaceutical compositions containing the compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the α2C adrenergic receptor agonists using such compounds or pharmaceutical compositions.

1 . A compound represented by the structural formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 A is a 5-membered heterocyclic ring containing 1-3 heteroatoms, and is substituted with at least one R 5 ;  
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 J 1 , J 2 , J 3 , and J 4  are independently —N—, —N(O)— or —C(R 2 )—, provided that 0-3 of J 1 , J 2 , J 3  and J 4  are —N—;  
 R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, C(═O)O—, —C(═NR 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and (═O), and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 , provided that when n is 3 or 4, no more than 2 of the R 3  groups may be (═O);  
 R 4  is independently selected from the group consisting of H and CN and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 ,—NR 7 R 7′ , —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 8  and —SO 2 NR 7 R 7′ ;  
 R 7  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6; and  
 w is 0-4.  
 with the following provisos:  
 (a) if J 1 -J 4  are each —C(H)—, n is 1, m is 1, R 4  is H, A is 3H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —C(═O)-naphthyl;  
 (b) if J 1 -J 4  are each —C(H)—, n is 1, m is 1, R 4  is H, A is 1H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —S(O 2 )-naphthyl; and  
 (c) if J 1 , J 2 , and J 4  are each —C(H)—, J 3  is —C(Br)—, n is 2, m is 1, R 3  is 3-benzyl, R 4  is H, A is 1H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —C(O 2 )benzyl.  
 
   
   
       2 . The compound of  claim 1 , wherein: 
 J 1 -J 4  are each —C(R 2 )—; 
 A is a 5-membered heterocyclic ring containing 1-3 heteroatoms, and is substituted with at least one R 5 ;  
   X is —O—, —S(O) p —, or —N(R 6 )—;    R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)N(R 7 R 7′ ) 2 , —P(═O)R 7 R 7′ , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;    Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═NR 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═N)R 7 )NR 7 O—, —S(O) p —, —SO 2 NR 7 —, —C(S)NR 7 —; 
 R 3  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —S(O) p R 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7 is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom together form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1 or 2;  
 n is 1 or 2;  
 p is 0-2;  
 q is 0-3; and  
 w is 0-4.  
   
   
   
       3 . The compound of  claim 2 , wherein A is imidazolyl.  
   
   
       4 . The compound of  claim 2 , wherein X is —O—.  
   
   
       5 . The compound of  claim 2 , wherein X is —N(R 6 )—.  
   
   
       6 . A compound represented by the structural formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 J 1 , J 2 , J 3 , and J 4  are independently —N—or —C(R 2 )—, provided that 0-3 of J 1 , J 2 , J 3  and J 4  are —N—;  
 R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═N)R 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, —SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 ,—NR 7 R 7′ , —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6;  
 z is 0-3; and  
 w is 0-4,  
 with the following provisos:  
 (a) if J 1 -J 4  are each —C(H)—, n is 1, m is 1, R 4  is H, A is 3H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —C(═O)-naphthyl;  
 (b) if J 1 -J 4  are each —C(H)—, n is 1, m is 1, R 4  is H, A is 1H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —S(O 2 )-naphthyl; and  
 (c) if J 1 , J 2 , and J 4  are each —C(H)—, J 3  is —C(Br)—, n is 2, m is 1, R 3  is 3-benzyl, R 4  is H, and X is —N(R 6 )—, then R 6  is not —C(O 2 )benzyl.  
 
   
   
       7 . A compound represented by the structural formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 R 1  is selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —SR 7 —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2. , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═NR 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, —SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 7 ) 2 , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, —CN, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6;  
 z is 0-3; and  
 w is 0-4,  
 with the following provisos:  
 (a) if n is 1, m is 1, R 4  is H, and X is —N(R 6 )—, then R 6  is not —C(═O)-naphthyl; and  
 (b) if n is 1, m is 1, R 4  is H, and X is —N(R 6 )—, then R 6  is not —S(O 2 )-naphthyl.  
 (c) if R 1  is Br, n is 2, m is 1, R 3  is 3-benzyl, R 4  is H, A is 1H-imidazol-4-yl, and X is —N(R 6 )—, then R 6  is not —C(O 2 )benzyl.  
 
   
   
       8 . The compound of  claim 7  wherein X is —O—, n is 1, m is 1, and R 4  is H.  
   
   
       9 . The compound of  claim 7 , wherein X is —N(R 6 )—, n is 1, m is 1, and R 4  is H.  
   
   
       10 . A compound represented by the structural formula:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 R 1  is selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —SR 7 —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7 ′, —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ; 
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 J 1 , J 2 , and J 4  are independently —N— or —C(R 2 )—, provided that 0-3 of J 1 , J 2 , and J 4  are —N—;  
 R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, C(═O)O—, —C(═NR 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , —S(O) p R 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —S(O) p R 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7 is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom together form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6;  
 z is 0-3; and  
 w is 0-4,  
 with the following provisos: 
 (a) if J 1 , J 2 , and J 4  are each —C(H)—, R 1  is H, n is 1, m is 1, R 4  is H, and X is —N(R 6 )—, then R 6  is not —C(═O)-naphthyl;  
 (b) if J 1 , J 2 , and j 4  are each —C(H)—, R 1  is H, n is 1, m is 1, R 4  is H, and X is —N(R 6 )—, then R 6  is not —S(O 2 )-naphthyl; and  
 
 (c) if J 1 , J 2 , and J 4  are each —C(H)—, R 1  is Br, n is 2, m is 1, R 3  is 3-benzyl, R 4  is H, and X is —N(R 6 )—, then R 6  is not —C(O 2 )benzyl.  
 
   
   
       11 . The compound of  claim 10 , wherein X is —O—, n is 1, m is 1, and R 4  is H.  
   
   
       12 . The compound of  claim 10 , wherein X is —N(R 6 )—, n is 1, m is 1, and R 4  is H.  
   
   
       13 . The compound of  claim 10 , wherein R 1  is selected from the group consisting of —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , and —(CH 2 ) q ON═CR 7 R 7′ .  
   
   
       14 . A compound selected from the group consisting of:  
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       15 . A pharmaceutical composition comprising at least one compound of  claim 1 , or a pharmaceutically acceptable salt or solvate thereof and at least one pharmaceutically acceptable carrier, adjuvant or vehicle.  
   
   
       16 . A pharmaceutical composition comprising at least one compound of  claim 14 , or a pharmaceutically acceptable salt or solvate thereof and at least one pharmaceutically acceptable carrier, adjuvant or vehicle.  
   
   
       17 . The pharmaceutical composition of  claim 15 , further comprising one or more additional therapeutic agents.  
   
   
       18 . The pharmaceutical composition of  claim 16 , further comprising one or more additional therapeutic agents.  
   
   
       19 . The pharmaceutical composition of  claim 17 , wherein said additional therapeutic agents are selected from the group consisting of anti-inflammatory steroids, PDE-4 inhibitors, anti-muscarinic agents, cromolyn sodium, H 1  receptor antagonists, 5-HT 1 , agonists, NSAIDs, angiotensin-converting enzyme inhibitors, angiotensin II receptor agonists, β-blockers, β-agonists, leukotriene antagonists, diuretics, aldosterone antagonists, ionotropic agents, natriuretic peptides, pain management agents, anti-anxiety agents, anti-migraine agents, and therapeutic agents suitable for treating heart conditions, psychotic disorders, and glaucoma.  
   
   
       20 . The pharmaceutical composition of  claim 18 , wherein said additional therapeutic agents are selected from the group consisting of steroids, PDE-4 inhibitors, anti-muscarinic agents, cromolyn sodium, H 1  receptor antagonists, 5-HT 1  agonists, NSAIDs, angiotensin-converting enzyme inhibitors, angiotensin II receptor agonists, β-blockers, β-agonists, leukotriene antagonists, diuretics, aldosterone antagonists, ionotropic agents, natriuretic peptides, pain management agents, anti-anxiety agents, anti-migraine agents, and therapeutic agents suitable for treating heart conditions, psychotic disorders, and glaucoma.  
   
   
       21 . A method for selectively stimulating α2C adrenergic receptors in a cell in need thereof, comprising contacting said cell with a therapeutically effective amount of at least one compound of formula I:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 A is a 5-membered heterocyclic ring containing 1-3 heteroatoms, and is substituted with at least one R 5 ;  
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 J 1 , J 2 , J 3 , and J 4  are independently —N—, —N(O)— or —C(R 2 )—, provided that 0-3 of J 1 , J 2 , J 3  and J 4  are —N—;  
 R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═N)R 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, —SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and (═O), and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 , provided that when n is 3 or 4, no more than 2 of the R 3  groups may be (═O);  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 ,—NR 7 R 7′ —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, —CN, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6; and  
 w is 0-4.  
 
   
   
       22 . A method for treating one or more conditions associated with α2C adrenergic receptors, comprising administering to a mammal in need of such treatment at least one compound of formula I:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate of said compound, wherein: 
 A is a 5-membered heterocyclic ring containing 1-3 heteroatoms, and is substituted with at least one R 5 ;  
 X is —O—, —S(O) p —, or —N(R 6 )—;  
 J 1 , J 2 , J 3 , and J 4  are independently —N—, —N(O)— or —C(R 2 )—, provided that 0-3 of J 1 , J 2 , J 3  and J 4  are —N—;  
 R 2  is independently selected from the group consisting of H, —OH, halo, —CN, —NO 2 , —(CH 2 ) q YR 7 , —(CH 2 ) q NR 7 YR 7′ , —(CH 2 ) q OYR 7 , —(CH 2 ) q ON═CR 7 R 7′ , —P(═O)(OR 7 )(OR 7′ ), —P(═O)(NR 7 R 7′ ) 2 , —P(═O)R 8   2 , and alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl groups optionally substituted with at least one R 5 ;  
 Y is selected from the group consisting of a bond, —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═N)R 7 )—, —C(═NOR 7 )—, —C(═NR 7 )NR 7 —, —C(═NR 7 )NR 7 O—, —S(O) p —, —SO 2 NR 7 —, and —C(S)NR 7 —;  
 R 3  is independently selected from the group consisting of H and (═O), and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 , provided that when n is 3 or 4, no more than 2 of the R 3  groups may be (═O);  
 R 4  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups optionally substituted with at least one R 5 ;  
 R 5  is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 ,—NR 7 R 7′ , —SR 7 , and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents;  
 R 6  is independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —SR 7  substituents, and —C(═O)R 7 , —C(═O)OR 7 , —C(═O)NR 7 R 7′ , —SO 2 R 7  and —SO 2 NR 7 R 7′ ;  
 R 7  is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 7′  is independently selected from the group consisting of selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; or 
 R 7  and R 7′  together with the nitrogen atom together form a 3- to 8-membered heterocyclyl, heterocyclenyl or heteroaryl ring having, in addition to the N atom, 1 or 2 additional hetero atoms selected from the group consisting of O, N, —N(R 9 )— and S, wherein said rings are optionally substituted by 1 to 5 independently selected R 5  moieties,  
 
 R 8  is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 9  is independently selected from the group consisting of H, —C(O)—R 10 , —C(O)—OR 10 , and —S(O) p —OR 10  and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents; and  
 R 10  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, —OH, —CN, —NO 2 , —N(R 11 ) 2 , and —SR 11  substituents;  
 R 11  is a moiety independently selected from the group consisting of H, —CN. alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;  
 m is 1-5;  
 n is 1-3;  
 p is 0-2;  
 q is 0-6; and  
 w is 0-4.  
 
   
   
       23 . The method of  claim 22 , wherein J 1 -J 4  are each —C(R 2 )—, n is 1, A is imidazolyl, and X is —O—.  
   
   
       24 . The method of  claim 22 , wherein J 1 -J 4  are each —C(H)—, n is 1, A is imidazolyl, and X is —O—.  
   
   
       25 . The method of  claim 22 , wherein J 1 -J 4  are each —C(R 2 )—, n is 1, A is imidazolyl, and X is —N(R 6 )—.  
   
   
       26 . The method of  claim 22 , wherein J 1 -J 4  are each —C(R 2 )—, n is 1, A is imidazolyl, and X is —S(O) p —.  
   
   
       27 . A method for treating one or more conditions associated with α2C adrenergic receptors, comprising administering to a mammal in need of such treatment a compound of  claim 14  or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       28 . The method of  claim 22 , wherein the conditions are selected from the group consisting of allergic rhinitis, congestion, pain, diarrhea, glaucoma, congestive heart failure, cardiac ischemia, manic disorders, depression, anxiety, migraine, stress-induced urinary incontinence, neuronal damage from ischemia and schizophrenia.  
   
   
       29 . The method of  claim 22 , wherein the conditions are selected from the group consisting of allergic rhinitis, congestion, pain, diarrhea, glaucoma, congestive heart failure, cardiac ischemia, manic disorders, depression, anxiety, and schizophrenia.  
   
   
       30 . The method of  claim 28 , wherein the condition is congestion.  
   
   
       31 . The method of  claim 29 , wherein the condition is congestion.  
   
   
       32 . The method of  claim 30 , wherein the congestion is associated with perennial allergic rhinitis, seasonal allergic rhinitis, non-allergic rhinitis, vasomotor rhinitis, rhinitis medicamentosa, sinusitis, acute rhinosinusitis, or chronic rhinosinusitis.  
   
   
       33 . The method of  claim 30 , wherein the congestion is caused by polyps or is virally induced.  
   
   
       34 . The method of  claim 31 , wherein the congestion is associated with perennial allergic rhinitis, seasonal allergic rhinitis, non-allergic rhinitis, vasomotor rhinitis, rhinitis medicamentosa, sinusitis, acute rhinosinusitis, or chronic rhinosinusitis.  
   
   
       35 . The method of  claim 31 , wherein the congestion is caused by polyps or is virally induced.  
   
   
       36 . The method of  claim 28 , wherein the condition is pain.  
   
   
       37 . The method of  claim 36 , wherein the pain is associated with neuropathy, inflammation, arthritis or diabetes.  
   
   
       38 . The method of  claim 24 , wherein the condition is pain.  
   
   
       39 . The method of  claim 38 , wherein the pain is associated with neuropathy, inflammation, arthritis or diabetes.  
   
   
       40 . A compound of  claim 1 , in isolated and purified form.  
   
   
       41 . A compound of  claim 1  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       42 . A compound of  claim 1  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       43 . A compound of  claim 1  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       44 . A compound of  claim 1  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       45 . A compound of  claim 1  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       46 . A method for the treatment of congestion in a mammal in need thereof which comprises administering to a mammal an effective dose of at least one compound having adrenergic activity wherein said compound is a functionally selective agonist of the α2c receptor.  
   
   
       47 . The method of  claim 46 , wherein the functionally selective agonist of the α2c receptor has an efficacy that is greater than or equal to 30% E max  when assayed in the GTPγS assay.  
   
   
       48 . A method for the treatment of congestion in a mammal in need thereof without modifying the blood pressure at a therapeutic dosewhich comprises administering to the mammal an effective dose of at least one compound having adrenergic activity wherein said compound is a functionally selective agonist of the α2c receptor.