Substituted fused imidazole derivatives, pharmaceutical compositions, and methods of use thereof

1. A method of treating a disease comprising administering to a human subject a compound,

wherein the disease is a cardiovascular disease; and

wherein the compound is a compound of Formula (I) or a pharmaceutically acceptable salt thereof

wherein

one of X 1 , X 2 , X 3 , and X 4 is

 and the remaining members of X 1 , X 2 , X 3 , and X 4 are independently N or

G is hydrogen, —C 1-8 alkyl, —C 3-10 cycloalkyl, —C 1-6 alkylene-C 3-10 cycloaklyl, heterocyclyl, —C 1-6 alkylene-C 3-10 heterocyclyl, phenyl, heteroaryl, or NR h R k , where the alkyl, alkylene, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R c ;

L is —CH 2 —C(O)N(R 6 )—, —C(O)N(R 6 )—, —C(O)—O—, —SO 2 —, —C(O)—, heteroarylene optionally substituted one or more times with substituents independently selected from R x , or heterocyclylene optionally substituted one or more times with substituents independently selected from R y ; or the group -L-G is -cyano;

R 1 is hydrogen, R a , phenyl, or heteroaryl, where the phenyl and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ;

R 2 is R b ;

R 3 is hydrogen, —C 1-6 alkyl, or —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R z ;

R 4 is —C 1-6 alkyl or —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R y ;

R 6 is hydrogen, —C 1-6 alkyl, —C 1-6 alkylene-C 3-10 cycloaklyl, where the alkyl, alkylene, and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R x ;

R a is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -cyano,

f) —CF 3 ,

g) —OCF 3 ,

h) —O—R d ,

i) —S(O) w —R d ,

j) —S(O) 2 O—R d ,

k) —NR d R e ,

l) —C(O)—R 4 ,

m) —C(O)—O—R d ,

n) —OC(O)—R d ,

o) —C(O)NR d R e ,

p) —C(O)-heterocyclyl,

q) —NR d C(O)R e ,

r) —OC(O)NR d R e ,

S) —NR d C(O)OR d , or

t) —NR d C(O)NR d R e ,

where the alkyl, cycloalkyl, and heterocyclyl groups are optionally substituted one or more times with substituents independently selected from R y ;

R b is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -phenyl,

f) -heteroaryl,

g) -cyano,

h) —CF 3 ,

i) —OCF 3 ,

j) —O—R f ,

k) —S(O) w —R f ,

I) —S(O) 2 O—R f ,

m) —NR f R g ,

n) —C(O)—R f ,

o) —C(O)—O—R f ,

p) —OC(O)—R f ,

q) —C(O)NR f R g ,

r) —C(O)-heterocyclyl,

s) —NR f C(O)R g ,

t) —OC(O)NR f R g ,

u) —NR f C(O)OR f , or

v) —NR f C(O)NR f R g ,

where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R z ;

R c is

a) -halogen,

b) —C 1-6 alkyl,

c) —C 3-10 cycloalkyl,

d) -heterocyclyl,

e) -cyano,

f) —CF 3 ,

g) —OCF 3 ,

h) —O—R h ,

i) —S(O) w —R h ,

j) —S(O) 2 O—R h ,

k) —NR h R k ,

I) —C(O)—R h ,

m) —C(O)—O—R h ,

n) —OC(O)—R h ,

o) —C(O)NR h R k ,

p) —C(O)-heterocyclyl,

q) —NR h C(O)R k ,

r) —OC(O)NR h R k ,

s) —NR h C(O)OR k ,

t) —NR h C(O)NR h R k ,

u) —NR h S(O) w R k ,

v) -phenyl,

w) -heteroaryl, or

x) —O—(C 1-4 alkylene)-O—(C 1-4 alkylene)-N(R h )C(O)—OR k ,

where the alkylene, alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ;

R d and R e are independently hydrogen, C 1-6 alkyl, or C 3-10 cycloalkyl, where the alkyl and cycloalkyl groups are optionally substituted one or more times with substituents independently selected from R x ; or, if R d and R e are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R y ;

R f and R g are independently hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R z ; or, if R f and R g are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R z ;

R h and R k are independently hydrogen, C 1-6 alkyl, C 3-10 cycloalkyl, heterocyclyl, phenyl, or heteroaryl, where the alkyl, cycloalkyl, heterocyclyl, phenyl, and heteroaryl groups are optionally substituted one or more times with substituents independently selected from R x ; or, if R h and R k are both attached to the same nitrogen atom, together with that nitrogen atom may optionally form a heterocyclic ring selected from the group consisting of azetidino, pyrrolidino, pyrazolidino, imidazolidino, oxazolidino, isoxazolidino, thiazolidino, isothiazolidino, piperidino, piperazino, morpholino, thiomorpholino, and azepano, where each ring is optionally substituted one or more times with substituents independently selected from R x ;

R y is

a) -halogen,

b) —NH 2 ,

c) -cyano,

d) -carboxy,

e) -hydroxy,

f) -thiol,

g) —CF 3 ,

h) —OCF 3 ,

i) —C(O)—NH 2 ,

j) —S(O) 2 —NH 2 ,

k) oxo,

l) —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

m) -heterocyclyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

n) —C 3-10 cycloalkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

o) —O—C 1-6 alkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

p) —O—C 3-10 cycloalkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

q) —NH—C 1-6 alkyl optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

r) —N(C 1-6 alkyl) 2 optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

s) —C(O)—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

t) —C(O)—O—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

u) —S—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

v) —S(O) 2 —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

w) —C(O)—NH—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

x) —C(O)—N(C 1-6 alkyl) 2 , optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

y) —S(O) 2 —NH—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

z) —S(O) 2 —N(C 1-6 alkyl) 2 , optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

aa) —NH—C(O)—C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 , or

bb) —NH—S(O) 2 —C 1-6 alkyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ;

R x is

a) —R y

b) -phenyl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

c) -heteroaryl, optionally substituted one or more times with substituents selected independently from the group consisting of halogen, —OH, —O—C 1-6 alkyl, —NH 2 , —NH—C 1-6 alkyl, and —N(C 1-6 alkyl) 2 ,

d) —O-phenyl,

e) —O-heteroaryl,

f) —C(O)-phenyl,

g) —C(O)-heteroaryl,

h) —C(O)—O-phenyl, or

i) —C(O)—O-heteroaryl;

R z is

a) —R y

b) -phenyl,

c) -heteroaryl;

d) —O-phenyl,

e) —O-heteroaryl,

f) —C(O)-phenyl,

g) —C(O)-heteroaryl,

h) —C(O)—O-phenyl, or

i) —C(O)—O-heteroaryl;

v is an integer from 0 to 4, and

w is an integer from 0 to 2.

2. The method of claim 1 , wherein the cardiovascular disease is selected from the group consisting of: hypertension, heart failure, hypercholesterolaemia, atherosclerosis, acute coronary thrombosis, deep vein thrombosis, peripheral vascular disease, congestive heart failure, acute coronary syndrome, failure of arterial fistula for dialysis, and primary pulmonary hypertension.

3. The method of claim 1 ,

wherein R 4 is -methyl, -ethyl, -isopropyl, -isobutyl, —CH 2 CH 2 —OCH 3 , —CH 2 CH 2 —F, —CH 2 CH 2 —NH 2 , or —CH 2 CH 2 —NH—CH 3 ; and

wherein R 3 is hydrogen.

4. The method of claim 1 , wherein X 3 is

and X 1 , X 2 , and X 4 are each

5. The method of claim 1 , wherein v is 1 and R 2 is attached at the 6-position of the benzothiazole ring.

6. The compound of claim 1 , wherein R 2 is fluoro, chloro, —CF 3 , or —OCF 3 .

7. The compound of claim 1 , wherein R 1 is hydrogen.

8. The compound of claim 1 , wherein R 4 is methyl.

9. The compound of claim 4 , wherein L is —C(O)NH—.

10. The compound of claim 4 , wherein G is C 1-8 alkyl optionally substituted one or more times with substituents independently selected from R c .

11. The compound of claim 10 , wherein G is C 1-8 alkyl optionally substituted once by —C(O)NR h R k .

12. The compound of claim 1 , wherein G is —CH 2 —C(O)NR h R k .

13. The compound of claim 10 , wherein G is C 1-8 alkyl optionally substituted once by —O—R h .

14. The compound of claim 13 , wherein G is —(CH 2 ) 2 —OR h .

15. The method of claim 1 , wherein the compound is selected from the group consisting of:

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-2-methyl-propyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide;

6-Fluoro-1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ethylamide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-fluoro-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-2-hydroxy-propyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-2-hydroxy-propyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-am ide;

1-Ethyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

1-(2-Methoxy-ethyl)-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-ethoxy-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-ethyl-1H-benzoimidazole-5-carboxylic acid (2-fluoro-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-ethyl-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-am ide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-2-hydroxy-propyl)-amide 2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)-ethyl]-amide

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-methoxy-ethoxy)-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-methoxy-ethoxy)-ethyl]-amide; and

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-dimethylamino-ethoxy)-ethyl]-amide;

or a pharmaceutically acceptable salt thereof.

16. The method of claim 1 , wherein the compound is selected from the group consisting of:

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid [2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (3-morpholin-4-yl-3-oxo-propyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-hydroxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-methoxy-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-dimethylamino-pyrrolidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-2-oxo-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((R)-3-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-((S)-3-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid [2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-methyl-2-morpholin-4-yl-2-oxo-ethyl)-amide; and

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [(R)-1-methyl-2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-amide;

or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein the compound is selected from the group consisting of:

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide;

1-M ethyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid methylcarbamoylmethyl-amide;

2-(6-Chloro-benzothiazol-2-ylamino)-1-methyl-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide;

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((S)-1-dimethylcarbamoyl-ethyl)-amide; and

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid ((R)-1-dimethylcarbamoyl-ethyl)-amide;

or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the compound is selected from the group consisting of:

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (2-ethanesulfonyl-ethyl)-amide; and

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (3-methanesulfonyl-propyl)-amide;

or a pharmaceutically acceptable salt thereof.

19. The method of claim 1 , wherein the compound is

3-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid dimethylcarbamoylmethyl-amide

or a pharmaceutically acceptable salt thereof.

20. The method of claim 1 , wherein the compound is

1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methoxy-ethyl)-amide

or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein the compound is

3-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (2-methoxy-ethyl)-amide

or a pharmaceutically acceptable salt thereof.

22. The method of claim 1 , wherein the compound is

1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid [2-(2-hydroxy-ethoxy)4-ethyl]-amide

or a pharmaceutically acceptable salt thereof.

23. The method of claim 1 , wherein the compound is

6-Methoxy-1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-morpholin-4-yl-ethyl)-amide

or a pharmaceutically acceptable salt thereof.

24. The method of claim 1 , wherein the compound is

3-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-3H-imidazo[4,5-b]pyridine-6-carboxylic acid (2-morpholin-4-yl-ethyl)-amide

or a pharmaceutically acceptable salt thereof.

25. A method of treating a disease comprising administering to a human subject a compound, wherein the cardiovascular disease; and

wherein the compound is a compound of Formula (I) or a pharmaceutically acceptable salt thereof

wherein

X 3 is

 and X 1 , X 2 , and X 4 are each

R 1 is hydrogen, —OCH 3 , or —F,

v is an integer from 0 to 2,

R 2 is —CI, —F, —CF 3 , or —OCF 3 ,

R 4 is -methyl, -ethyl, -isopropyl, or -isobutyl,

L is —C(O)N(R 6 )—,

R 6 is hydrogen, and

G is —H, -methyl, -ethyl, -n-propyl, -isopropyl, -isobutyl, —CH 2 Y 3 , —CH 2 CH 2 Y 3 , —CH 2 CH 2 CH 2 Y 3 , —CH(CH 3 )CH 2 Y 3 , —CH 2 CH(Y 3 )CH 3 , —CH(Y 3 )CH 3 , —CH 2 C(Y 3 )(CH 3 ) 2 , or —C(Y 3 )(CH 3 ) 2 ,

where

Y 3 is -cyclopropyl, —CF 3 , —OCH 3 , —OCH 2 CH 3 , —F, —OH, —O(CH 2 ) 2 —OH, - O(CH 2 ) 2 —F, —SCH 3 , —S(O) 2 —CH 3 , —SCH 2 CH 3 , —S(O) 2 CH 2 CH 3 , —NH—CH 3 , —NH—CH 2 CH 3 , —N(CH 3 ) 2 , —NH—C(O)—CH 3 , —NH—C(O)—CH 2 CH 3 , or C(O)—Y 4 ,

where

Y 4 is —OH, —OCH 3 , —OCH 2 CH 3 , —OC(CH 3 ) 3 , —NH 2 , —NH—CH 3 , —NH—CH 2 CH 3 , —N(CH 3 ) 2 , or —N(CH 2 CH 3 ) 2 .

26. The method of claim 25 , wherein the cardiovascular disease is selected from the group consisting of hypertension, heart failure, hypercholesterolaemia, atherosclerosis, acute coronary thrombosis, deep vein thrombosis, peripheral vascular disease, congestive heart failure, acute coronary syndrome, failure of arterial fistula for dialysis, and primary pulmonary hypertension.

27. A method of treating a disease comprising administering to a human subject a compound, wherein the disease is a cardiovascular disease, and wherein the compound is 1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid dimethylcarbamoylmethyl-amide or a pharmaceutically acceptable salt thereof.

28. The method of claim 27 , wherein the cardiovascular disease is selected from the group consisting of hypertension, heart failure, hypercholesterolaemia, atherosclerosis, acute coronary thrombosis, deep vein thrombosis, peripheral vascular disease, congestive heart failure, acute coronary syndrome, failure of arterial fistula for dialysis, and primary pulmonary hypertension.