Pyridine derivative potassium channel inhibitors

1. A compound of formula I,

or a pharmaceutically acceptable salt, or an optical isomer thereof, wherein:

A is selected from the group consisting of

1) an aryl ring, and

2) a 6-membered unsaturated monocyclic heteroaryl ring with 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, O and S, wherein the point of attachment to the heteroaryl ring is a carbon atom,

wherein said aryl or heteroaryl ring is unsubstituted, mono-substituted with R 1 , disubstituted with groups independently selected from R 1 , trisubstituted with groups independently selected from R 1 , or tetrasubstituted with groups independently selected from R 1 , and wherein any stable S or N heteroaryl or heterocyclic ring atom is unsubstituted or substituted with oxo;

D is selected from the group consisting of

1) a saturated 4-6 membered heterocyclic ring with 1, 2, 3, or 4 heteroatom ring atoms independently selected from the group consisting of N, O or S, wherein the point of attachment to the heterocyclic ring is a nitrogen atom, wherein said heterocyclic ring is unsubstituted, monosubstituted with R 2 or di-substituted with groups independently selected from R 2 ,

2)—NH(CH 2 ) n CH 3 , and

3) —NH(CH 2 ) n CF 3 ;

R 1 is independently selected from the group consisting of halogen and CN;

R 2 is independently selected from the group consisting of halogen;

R 4 is independently selected from the group consisting of hydrogen, halogen and CF 3 ;

R 5 is independently selected from the group consisting of hydrogen, halogen, CF 3 , OCF 3 , and C 1-6 alkyl; and

n is 1, 2, 3, 4, 5, or 6.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein A is selected from the group consisting of

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein A is selected from the group consisting of

4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein A is selected from the group consisting of

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein D is selected from the group consisting of

—NH(CH 2 ) n CH 3 , and NH(CH 2 ) n CF 3 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein R 1 is independently selected from the group consisting of F and CN, and R 2 is F.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, wherein R 4 is independently selected from the group consisting of hydrogen, Cl, F, and CF 3 , and R 5 is independently selected from the group consisting of hydrogen, Cl, F, CF 3 , OCF 3 , and CH 3 .

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-piperidin-1-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-pyrrolidin-1-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4-fluorophenyl)-2-morpholin-4-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4,4-difluoropiperidin-1-yl)-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-[(2,2,2-trifluoroethyl)amino]ethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4-fluorophenyl)-2-pyrrolidin-1-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4-fluorophenyl)-2-piperidin-1-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4,4-difluoropiperidin-1-yl)-2-(4-fluorophenyl)ethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(3,3-difluoropyrrolidin-1-yl)-2-pyridin-3-ylethanol,

(+/−)4-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-morpholin-4-ylethyl}benzonitrile,

(+/−)4-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-pyrrolidin-1-ylethyl}benzonitrile,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-2-ylethanol,

(+/−)-2-azetidin-1-yl-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-(4-fluoropiperidin-1-yl)-2-pyridin-3-ylethanol,

(+/−)3-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-morpholin-4-ylethyl}benzonitrile,

(+/−)4-{1-azetidin-1-yl-2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxyethyl}benzonitrile,

(+/−)4-[2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-1-(3,3-difluoropyrrolidin-1-yl)-2-hydroxyethyl]benzonitrile,

(+/−)4-[2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-1-(4,4-difluoropiperidin-1-yl)-2-hydroxyethyl]benzonitrile,

(+/−)4-[2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-1-(4-fluoropiperidin-1-yl)-2-hydroxyethyl]benzonitrile,

(+/−)-2-morpholin-4-yl-2-pyridin-2-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-morpholin-4-yl-2-pyridin-2-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-morpholin-4-yl-2-pyridin-2-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-pyridin-3-yl-2-pyrrolidin-1-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-pyridin-3-yl-2-pyrrolidin-1-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-piperidin-1-yl-2-pyridin-2-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-2-yl-2-pyrrolidin-1-ylethanol,

(+/−)-2-azetidin-1-yl-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-2-ylethanol,

(+/−)-2-(3,3-difluoropyrrolidin-1-yl)-2-pyridin-3-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-(3,3-difluoropyrrolidin-1-yl)-2-pyridin-3-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-pyrrolidin-1-ylethanol,

(1R or S,2S or R)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-pyrrolidin-1-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-pyrrolidin-1-ylethanol,

(1R or S,2S or R)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-pyridin-3-yl-2-pyrrolidin-1-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(1R or S,2S or R)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(1R or S,2S or R)-1-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)3-(2-hydroxy-1-pyrrolidin-1-yl-2-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethyl)benzonitrile,

(+/−)3-(2-hydroxy-1-morpholin-4-yl-2-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethyl)benzonitrile,

(+/−)3-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-pyrrolidin-1-ylethyl}benzonitrile,

(+/−)3-{1-azetidin-1-yl-2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxyethyl} benzonitrile,

(+/−)-2-pyridin-2-yl-2-pyrrolidin-1-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-2-azetidin-1-yl-2-pyridin-2-yl-1-{2-[3-(trifluoromethyl)phenyl]pyridin-3-yl}ethanol,

(+/−)-1-[2-(2,3-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(2-chlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(3-chlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-[2-(2,4-dichlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)4-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-piperidin-1-ylethyl}benzonitrile,

(+/−)4-{2-[2-(3,5-dichlorophenyl)pyridin-3-yl]-2-hydroxy-1-[(2,2,2-trifluoroethyl)amino]ethyl}benzonitrile,

(+/−)-1-{2-[3,5-bis(trifluoromethyl)phenyl]pyridin-3-yl}-2-morpholin-4-yl-2-pyridin-3-ylethanol,

(+/−)-1-{2-[4-chloro-3-(trifluoromethyl)phenyl]pyridin-3-yl}-2-morpholin-4-yl-2-pyridin-3-ylethanol, and

(+/−)-1-[2-(4-chlorophenyl)pyridin-3-yl]-2-morpholin-4-yl-2-pyridin-3-ylethanol.

9. A method for treating atrial fibrillation in a patient, comprising administering a compound of claim 1 to the patient.

10. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the compound claim 1 or a pharmaceutically acceptable salt thereof.