Polycyclic pyrimidines as potassium ion channel modulators

1. A compound having a structure according to Formula I:

or a pharmaceutically acceptable salt thereof,

wherein

s is an integer from 1 to 4;

R 1 is H, —OH, —NO 2 , —SO 2 NH 2 , halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted 3- to 7- membered cycloalkyl, substituted or unsubstituted 5- to 7- membered heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —NR 7 R 8 , wherein R 7 and R 8 are independently H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted 5- to 7- membered cycloalkyl, substituted or unsubstituted 5- to 7- membered heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R 7 and R 8 are optionally joined together with the nitrogen to which they are attached to form a substituted or unsubstituted 5- to 7- membered heterocycloalkyl, or substituted or unsubstituted heteroaryl;

each R 2 is independently —H or —OCH 3; and

R 3 is H, —NH 2 , —NO 2 , halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted 3- to 7- membered cycloalkyl, substituted or unsubstituted 5- to 7- membered heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

wherein two R 3 groups are optionally joined together with the atoms to which they are attached to form a substituted or unsubstituted ring.

2. The compound of claim 1 , wherein

R 1 is H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or substituted or unsubstituted aryl; and

R 3 is H, —NH 2 , —NO 2 , halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

3. The compound of claim 2 , wherein

R 1 is H, methyl, —NH 2 , or unsubstituted phenyl;

R 2 is H, or —OCH 3 ; and

R 3 is H, —NH 2 , —NO 2 , Cl, Br, F, methyl, phenyl, fluorophenyl, —CF 3 , —OCH 3 , dimethylamino, unsubstituted piperidine, p-methyl morpholino, unsubstituted pyrrolidinonyl, unsubstituted 2-thiophenyl, unsubstituted 3-thiophenyl, unsubstituted furanyl, or n-methyl piperizinyl.

4. The compound of claim 1 , wherein R 3 is Cl or —NR 7 R 8 ,

wherein R 7 and R 8 are independently H, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted 5- to 7-membered cycloalkyl, substituted or unsubstituted 5- to 7-membered heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R 7 and R 8 are optionally joined together with the nitrogen to which they are attached to form a substituted or unsubstituted 5- to 7-membered heterocycloalkyl, or substituted or unsubstituted heteroaryl.

5. The compound of claim 4 , wherein R 3 is Cl, —NH 2 , —N(CH 3 ) 2 ,

6. A metal complex, comprising a polyvalent metal ion and a polydentate component of a metal ion chelator, wherein said polydentate component is a compound according to claim 1 .

7. The complex of claim 6 , wherein said polyvalent metal ion is selected from iron, zinc, copper, cobalt, manganese, and nickel.

8. A method of treating a disorder or condition through modulation of a potassium ion channel, said method comprising administering to a subject in need of such treatment, an effective amount of an SK channel modulatory compound of claim 1 , wherein the disease is selected from the group consisting of epilepsy, seizures, learning and memory deficits, mood disorders, Parkinson's disease, and psychotic disorders.

9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the compound of claim 1 .

10. The compound of claim 3 , wherein R 1 is —H, (R 2 ) 2 are —H and —OCH 3 , and R 3 is —Cl.

11. The compound of claim 10 , wherein the compound is selected from the group consisting of:

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-pyrrolidin-1-yl-pyridin-2-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-thiophen-2-yl-pyridin-2-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(4-methyl-3,4,5,6-tetrahydro-2H-[1,3′]bipyridinyl-6′-yl)-amine,

(5-Methoxy-pyridin-2-yl)-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-thiophen-3-yl-pyridin-2-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-pyridin-2-yl-amine,

(5-Chloro-pyridin-2-yl)-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine,

N 2 -(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-N5,N5-dimethyl-pyridine-2,5-diamine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-phenyl-pyridin-2-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-[5-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-[5-(5-methyl-furan-2-yl)-pyridin-2-yl]-amine,

[5-(3-Fluoro-phenyl)-pyridin-2-yl]-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine,

(5-Fluoro-pyridin-2-yl)-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine,

[2-(6-Methyl-pyridin-2-yl)-pyrimidin-4-yl]-pyridin-2-yl-amine,

(5-Chloro-pyridin-2-yl)-(2-pyridin-2-yl-pyrimidin-4-yl)-amine,

(6-Methyl-2-pyridin-2-yl-pyrimidin-4-yl)-pyridin-2-yl-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-nitro-pyridin-2-yl)-amine,

(5 -Bromo-pyridin-2-yl)-(5-methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-amine,

(5-Methoxy-2-pyridin-2-yl-pyrimidin-4-yl)-(5-trifluoromethyl-pyridin-2-yl)-amine and

(5-Chloro-6-methyl-2-pyridin-2-yl-pyrimidin-4-yl)-(5-trifluoromethyl-pyridin-2-yl)-amine.

12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the compound of claim 11 .

13. A method of treating a disease through modulation of a potassium ion channel, said method comprising administering to a subject in need of such treatment, an effective amount of a SK channel modulatory compound of claim 11 , wherein the disease is selected from the group consisting of epilepsy, seizures, learning and memory deficits, mood disorders, Parkinson's disease, and psychotic disorders.

14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the compound of claim 10 .

15. A method for treating a disease through modulation of a potassium ion channel, said method comprising administering to a subject in need of such treatment, an effective amount of a SK channel modulatory compound of claim 10 , wherein the disease is selected from the group consisting of epilepsy, seizures, learning and memory deficits, mood disorders, Parkinson's disease, and psychotic disorders.