Functionally selective alpha2C adrenoreceptor agonists

1. A compound represented by the structural formula:

or a pharmaceutically acceptable salt of said compound, wherein:

J 1 , J 2 and J 3 are —C(R 2 )—;

is a single or double bond;

R 1 is —(CH 2 ) q NR 7 YR 7′ ;

Y is selected from the group consisting of —C(═O)—, —C(═O)NR 7 —, —C(═O)O—, —C(═NR 7 )NR 7 —, —S(O) p —, and —SO 2 NR 7 ;

R 2 is independently selected from the group consisting of H, —OH, halo, and —CN, and alkyl and alkoxy optionally substituted with at least one R 5 ;

R 3 is independently selected from the group consisting of H and alkyl and alkoxy optionally substituted with at least one R 5 ;

R 4 is independently selected from the group consisting of H and alkyl;

R 5 is independently selected from the group consisting of H, halo, —OH, —CN, —NO 2 , —NR 7 R 7′ , and —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 7 is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, alkoxy, —OH, —CN, —NO 2 , —N(R 11 ) 2 and —S(O) p R 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;

R 11 is a moiety independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;

m is 1-5;

n is 1;

p is 0-2;

q is 0;

w is 1-3; and

z is 0.

2. A compound according to claim 1 , which is represented by the structural formula:

or a pharmaceutically acceptable salt or solvate of said compound, wherein:

X is H or halo;

R 1 is —(CH 2 ) q NR 7 YR 7′ ;

Y is selected from the group consisting of a —C(═O)NR 7 — and —C(═O)O—;

R 4 is independently selected from the group consisting of H and alkyl,

R 7 is independently selected from the group consisting of H and alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl, heteroaryl, and heteroarylalkyl groups, each of which is optionally substituted with at least one of halo, alkoxy, —OH, —CN, —NO 2 , —N(R 11 ) 2 and —S(O) p R 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 11 is a moiety independently selected from the group consisting of H and alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;

m is 1-5;

p is 0-2; and

q is 0;

or a pharmaceutically acceptable salt of said compound.

3. The compound of claim 2 , wherein m is 1 and R 4 is H.

4. A compound that is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

5. A compound of claim 1 , having the formula:

or a pharmaceutically acceptable salt thereof.

6. A compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

7. A compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 having the formula:

or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 , in isolated and purified form.

11. A solid pharmaceutical composition comprising at least one compound of claim 1 , or a pharmaceutically acceptable salt and at least one pharmaceutically acceptable carrier, adjuvant or vehicle.

12. A solid pharmaceutical composition comprising at least one compound of claim 4 , or a pharmaceutically acceptable salt and at least one pharmaceutically acceptable carrier, adjuvant or vehicle.

13. The pharmaceutical composition of claim 11 , additionally further comprising one or more additional therapeutic agents.

14. The pharmaceutical composition of claim 12 , additionally further comprising one or more additional therapeutic agents.

15. The pharmaceutical composition of claim 13 , 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 NSAIDs, angiotensin-converting enzyme inhibitors, angiotensin II receptor agonists, β-blockers, β-agonists, leukotriene antagonists, diuretics, aldosterone antagonists, ionotropic agents, pain management agents, anti-anxiety agents, and anti-migraine agents.

16. The pharmaceutical composition of claim 14 , 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, NSAIDs, angiotensin-converting enzyme inhibitors, angiotensin II receptor agonists, β-blockers, β-agonists, leukotriene antagonists, diuretics, aldosterone antagonists, ionotropic agents, pain management agents, anti-anxiety agents, and anti-migraine agents.

17. The pharmaceutical composition according to claims 13 wherein therapeutic agents are selected from the group consisting of 5-HT 1 agonists, natriuretic peptides, therapeutic agents suitable for treating heart conditions, psychotic disorders, and glaucoma.