Potassium channel inhibitors

1. A compound of formula I, or a pharmaceutically acceptable salt thereof, having the formula I:

wherein:

A and B are independently selected from the group consisting of

a pyridyl ring, wherein the point of attachment to the pyridyl ring is a carbon atom,

wherein said pyridyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N pyridyl ring atom is unsubstituted or substituted with oxo, said pyridyl ring R 4 substitutions being on one or more pyridyl ring carbon atoms

C is a phenyl ring, wherein said phenyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 ;

D is selected from the group consisting of:

a heteroaryl ring, wherein the point of attachment to the heteroaryl ring is a carbon atom, and the heteroaryl ring is selected from the group consisting of: a 4-6 membered saturated heterocyclic ring with 1, 2 or 3 heteroatom ring atoms selected from the group consisting of N, O and S, wherein the point of attachment to the heterocyclic ring is a carbon atom,

wherein said heteroaryl or saturated heterocyclic ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable S or N heteroaryl or heterocyclic ring atom is unsubstituted or substituted with oxo, said heteroaryl ring R 4 substitutions being on one or more heteroaryl ring carbon atoms;

X and Y are independently selected from the group consisting of H and OR 5 and —NHS(O)R 5 ;

R a , in each instance in which it appears, is independently selected from the group consisting of

1) hydrogen,

2) C 1 -C 6 alkyl,

3) halogen,

4) aryl,

5) heterocycly,

6) C 3 -C 10 cycloalkyl, and

7) OR 5 ,

said alkyl, aryl, heterocyclyl and cycloalkyl is unsubstituted or substituted with at least one substituent selected from R 6 ,

R 4 , in each instance in which it appears, is independently selected from the group consisting of

1) hydrogen,

2) halogen,

3) NO 2 ,

4) CN,

5) CR 4 ═C(R 5 ) 2 ,

6) C≡CR 5 ,

7) (CR a 2 ) n OR 5 ,

8) (CR a 2 ) n N(R 5 ) 2 ,

9) (CR a 2 ) n C(O)R 5 ,

10) (CR a 2 ) n C(O)OR 5 ,

11) (CR a 2 ) n R 5 ,

12) (CR a 2 ) n S(O)mR 5 ,

13) (CR a 2 ) n S(O) m N(R 5 ) 2 ,

14) OS(O) m R 5 ,

15) N(R 5 )C(O)R 5 ,

16) N(R 5 )S(O) m R 5 ,

17) (CR a 2 ) n N(R 6 )R 5 ,

18) (CR a 2 ) n N(R 5 )(CR a 2 ) n C(O)N(R 5 ) 2 ,

19) (CR a 2 ) n N(R 5 )(CR a 2 ) n C(O)OR 5 ,

20) N(R 5 )(CR a 2 ) n R 5 ,

21) N(R 5 )(CR a 2 ) n N(R 5 ) 2 ,

22) (CR a 2 ) n C(O)N(R 5 ) 2 ,

23) N 3 , and

22) =O;

R 5 , in each instance in which it appears, is independently selected from the group consisting of

1) hydrogen,

2) unsubstituted or substituted C 1 -C 6 alkyl,

3) unsubstituted or substituted C 3 -C 10 cycloalkyl,

4) unsubstituted or substituted aryl,

5) unsubstituted or substituted heterocycle,

6) CF 3 ,

7) unsubstituted or substituted C 2 -C 6 alkenyl, and

8) unsubstituted or substituted C 2 -C 6 alkynyl,

or in the case where R 5 is attached to a nitrogen atom that is disubstituted with R 5 , each R 5 is independently selected from C 1 -C 6 alkyl, and the nitrogen atom together with each R 5 form a ring;

R 6 , in each instance in which it appears, is independently selected from the group consisting of

1) hydrogen,

2) unsubstituted or substituted C 1 -C 6 alkyl,

3) halogen,

4) OR 5 ,

5) CF 3 ,

6) unsubtituted or substituted aryl,

7) unsubstituted or substituted C 3 -C 10 cycloalkyl,

8) unsubstituted or substituted heterocycle,

9) S(O) m N(R 5 ) 2 ,

10) C(O)OR 5 ,

11) C(O)R 5 ,

12) CN,

13) C(O)N(R 5 ) 2 ,

14) N(R 5 )C(O)R 5 ,

15) N(R 5 )C(O)OR 5 ,

16) N(R 5 )C(O)N(R 5 ) 2 ,

17) OC(O)N(R 5 ) 2 ,

18) S(O) m R 5 ,

19) OS(O) m R 5 ,

20) NO 2 , and

21) N(R 5 ) 2 ;

m is independently 0, 1 or 2; and

n is independently 0, 1, 2, 3, 4, 5 or 6.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

A is a pyridyl ring, wherein the point of attachment to the pyridyl ring is a carbon atom

wherein said pyridyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R4, trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N pyridyl ring atom is unsubstituted or substituted with oxo, said pyridyl ring R 4 substitutions being on one or more pyridyl ring carbon atoms;

B is a pyridyl ring, wherein the point of attachment to the pyridyl ring is a carbon atom, and the heteroaryl ring is selected from the group consisting of:

wherein said pyridyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N pyridyl ring atom is unsubstituted or substituted with oxo, said pyridyl ring R 4 substitutions being on one or more pyridyl ring carbon atoms;

C a phenyl ring,

wherein said phenyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from or tetrasubstituted with groups independently selected from R 4;

D is selected from the group consisting of:

1) a heteroaryl ring, wherein the point of attachment to the heteroaryl ring is a carbon atom, and the heteroaryl ring is selected from the group consisting of:

a) a 5-membered unsaturated monocyclic ring with 1, 2, 3, or 4 heteroatom ring atoms selected from the group consisting of N, O or S, and

b) a 6-membered unsaturated monocyclic ring with 1, 2, 3, or 4 heteroatom ring atoms selected from the group consisting of N, O or 5, and

2) a 5-membered saturated heterocyclic ring with 1, 2 or 3 heteroatom ring atoms selected from the group consisting of N, O and S, wherein the point of attachment to the heterocyclic ring is a carbon atom,

wherein said heteroaryl or saturated heterocyclic ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable S or N heteroaryl or heterocyclic ring atom is unsubstituted or substituted with oxo, said heteroaryl ring R 4 substitutions being on one or more heteroaryl ring carbon atoms; and

X and Y are independently selected from the group consisting of H, OR 5 , and —NHS(O)R 5 .

3. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein

A is a pyridyl ring, wherein the point of attachment to the pyridyl ring is a carbon atom,

wherein said pyridyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N pyridyl ring atom is unsubstituted or substituted with oxo, said heteroaryl ring R 4 substitutions being on one or more heteroaryl ring carbon atoms;

B is a pyridyl ring, wherein the point of attachment to the pyridyl ring is a carbon atom,

wherein said pyridyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N pyridyl ring atom is unsubstituted or substituted with oxo, said pyridyl ring R 4 substitutions being on one or more pyridyl ring carbon atoms;

C is a phenyl ring

wherein said phenyl ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , ; and

D is selected from the group consisting of:

1) a heteroaryl ring, wherein the point of attachment to the heteroaryl ring is a carbon atom, and the heteroaryl ring is selected from the group consisting of:

a) a 5-membered unsaturated monocyclic ring with 4 N ring atoms, and

b) a 6-membered unsaturated monocyclic ring with 1 or 2 N ring atoms, and

2) a 5-membered saturated heterocyclic ring with I N ring atom, wherein the point of attachment to the heterocyclic ring is a carbon atom,

wherein said heteroaryl or saturated heterocyclic ring is unsubstituted, mono-substituted with R 4 , disubstituted with groups independently selected from R 4 , trisubstituted with groups independently selected from R 4 , or tetrasubstituted with groups independently selected from R 4 , and wherein any stable N heteroaryl or heterocyclic ring atom is unsubstituted or substituted with oxo, said heteroaryl ring R 4 substitutions being on one or more heteroaryl ring carbon atoms.

4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein

X is selected from the group consisting of hydrogen and —OH;

Y is selected from the group consisting of hydrogen, —OH and —NHS(O)C(CH 3 ) 3;

A is selected from the group consisting of

B is selected from the group consisting of

C is selected from the group consisting of

D is selected from the group consisting of

5. A compound of claim 4 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of

(R)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(S)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(R)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(S)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(±)-2-fluoro-5-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine,

(±)-3-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine,

(±)-2-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine,

(±)-3-[2-(4-fluorophenyl)-1-pyridin-3-yl-2-pyridin-4-ylethyl]pyridine,

(±)-2-chloro-3-[2-(4-fluorophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridine,

(±)-2-chloro-3-[2-(4-fluorophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridine,

(±)-2-chloro-3-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine,

(±)-2-fluoro-5-[2-(4-fluorophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridine,

(±)-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]-N,N-dimethylpyridin-2-amine,

(±)-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-arnine,

(±)-2-({6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethanol,

(±)-N-ethyl-N′-1[2-({6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethyl]urea,

(±)-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridine-2-carboxarnide,

(±)-methyl 3-(1-pyridin-2-yl-2,2-dipyridin-3-ylethyl)benzylcarbamate,

(±)-methyl 4-(1-pyridin-2-yl-2,2-dipyridin-3-ylethyl)benzylcarbamate,

(±)-3-(1-pyridin-2-yl-2,2-dipyridin-3-ylethyl)benzamide,

(±)-3-(1-pyridin-2-yl-2,2-dipyridin-3-ylethyl)benzoic acid,

(±)-6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-amine,

(±)-2-({3-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethanol,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}acetamide,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(±)-N-[2-({6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethyl]methanesulfonamide,

(±)-5-[2-(4-fluorophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridin-2-amine,

(±)-5-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-amine,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}glycine,

(±)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}urea,

(±)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}acetamide,

(±)-N-[2-({6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethyl]acetamide,

(±)-N-[2-({6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}amino)ethyl]methanesulfonamide,

(±)-N-{6-[1(4-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}-N′-methylurea,

(±)-tert-butyl N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}glycinate,

(±)-N-{6-[2-(3-cyanophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridin-2-yl}acetamide,

(±)-N-{6-[2-(3-cyanophenyl)-2-pyridin-2-yl-1-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(±)-N-[6-(2-phenyl-2-pyridin-2-yl-1-pyridin-3-ylethyl)pyridin-2-yl]methanesulfonamide,

(±)-N-[6-(2-phenyl-1,2-dipyridin-3-ylethyl)pyridin-2-yl]methanesulfonamide,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}urea,

(±)-6-(2-phenyl-1,2-dipyridin-3-ylethyl)pyridin-2(1 H)-one,

(±)-1-phenyl-2,2-dipyridin-3-yl-1-pyrimidin-2-ylethanol,

(±)-tert-Butyl 2-(2-hydroxy-1-phenyl-2,2-dipyridin-3-ylethyl)pyrrolidine- 1-carboxylate,

(±)-methyl 6-[1-(4-fluorophenyl)-2,2-bis(2-fluoropyridin-3-yl)ethyl]pyridin-2-ylcarbamate,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-bis(2-fluoropyridin-3-yl)ethyl]pyridin-2-yl}methanesulfonamide,

(±)-N-{6-[1-(4-fluorophenyl)-2,2-bis(2-fluoropyridin-3-yl)ethyl]pyridin-2-yl}urea,

(±)-methyl 6-[1-(4-fluorophenyl)-2,2-bis(5-methoxypyridin-3-yl)ethyl ]pyridin-2-ylcarbarnate,

(±)-N-{6-[2,2-bis(6-chloropyridin-3-yl)-1-(4-fluorophenyl)ethyl]pyridin-2-yl}methanesulfonamide,

(±)-N-{6-[2,2-bis(6-aminopyridin-3-yl)-1-(4-fluorophenyl)ethyl]pyridin-2-yl}methanesulfonamide,

3-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]-2-piperidin-1-ylpyridine,

N-{4-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-2-yl}methanesulfonamide,

N-{5-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

N-{5-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}acetamide,

5-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}-1,3,4-thiadiazol-2-amine,

6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]-N-pyridin-3-ylpyridin-2-amine,

4-[2-(6-aminopyridin-2-yl)-1-(4-chlorophenyl)-2-pyridin-3-ylethyl]pyrimidin-2-amine,

4-[1,2,2-tris(6-aminopyridin-2-yl)ethyl]fluorobenzene,

N-{6-[1-(4-fluorophenyl)-2,2-bis(6-methoxypyridin-3-yl)ethyl]pyridin-2-yl}methanesulfonamide,

(±)-6-[1-(4-fluorophenyl)-2-(6-aminopyridin-3-yl)-2-(6-methoxypyridin-2-ylethyl]pyridin-2-amine,

N˜2˜-{4-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-2-yl}-N1,N1-dimethylglycinamide,

N-{6-[1-(4-fluorophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

N-{6-[1-(4-fluorophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

methyl 6-[1-(4-fluorophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-ylcarbamate,

methyl 6-[1-(4-fluorophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-ylcarbarnate,

N-{6-[1-(3,4-dichlorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

N-{6-[1-(4-chlorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

N-(6-{2,2-dipyridin-3-yl-1-[4-(trifluoromethyl)phenyl]ethyl}pyridin-2-yl)methanesulfonamide,

4-[1-(4-chlorophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-2-amine,

N-{6-[1-(4-chlorophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

4-[1-(4-chlorophenyl)-2,2-dipyridin-3-ylethyl]-n-methylpyrimidin-2-amine,

N-{6-[1-(4-cyanophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

N-{6-[1-(4-cyanophenyl)-2-(2-fluoropyridin-3-yl)-2-pyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

4-[1-(3,4-dichlorophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-2-amine,

4-{2,2-dipyridin-3-yl-1-[4-(trifluoromethyl)phenyl]ethyl}pyrimidin-2-amine,

methyl 6-[1-(2-aminopyrimidin-4-yl)-2-(4-chlorophenyl)-2-pyridin-3-ylethyl]pyridin-2-ylcarbamate,

N-{2-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-4-yl}methanesulfonamide,

N-{4-[1-(3-bromophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-2-yl}methanesulfonamide,

2-[1-(3-chlorophenyl)-2,2-dipyridin-3-ylethyl]-4-(methylthio)pyrimidine, and

2-[1-(3-chlorophenyl)-2,2-dipyridin-3-ylethyl]pyrimidin-4-amine.

6. A compound of claim 5 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of

(R)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(S)-N-{6-[1-(4-fluorophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide,

(R)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide, and

(S)-N-{6-[1-(3-cyanophenyl)-2,2-dipyridin-3-ylethyl]pyridin-2-yl}methanesulfonamide.

7. A compound or a pharmaceutically acceptable salt thereof, which is

8. A method of treating a condition in a mammal, the treatment of which is effected or facilitated by K v 1.5 inhibition, which comprises administering a compound of claim 1 in an amount that is effective at inhibiting K v 1.5.wherein the condition is cardiac arrythmia and atrial ffibrillation.

9. A method of claim 8 , wherein the condition is cardiac arrythmia.

10. A method of claim 9 , wherein the cardiac arrythmia is atrial fibrillation.

11. A method of treating cardiac arrythmia comprising administering a compound of claim 1 with a compound selected from one of the classes of compounds consisting of antiaffhythmic agents having Kv1.5 blocking activities, ACE inhibitors, angiotensin II antagonists, cardiac glycosides, L-type calcium channel blockers, T-type calcium channel blockers, selective and nonselective beta blockers, endothelin antagonists, thrombin inhibitors, aspirin, nonselective NSAIDs, warfarin, factor Xa inhibitors, low molecular weight heparin, unfractionated heparin, clopidogrel, ticlopidine, IIb/IIIa receptor antagonists, 5HT receptor antagonists, integrin receptor antagonists, thromboxane receptor antagonists, TAFI inhibitors and P2T receptor antagonists.

12. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the compound claim 1 or a pharmaceutically acceptable crystal form or hydrate thereof.

13. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the compound claim 1 or a pharmaceutically acceptable crystal form orhydrate thereof.