Pyrrole derivatives and their methods of use

1. A compound of the formula (I):

or a pharmaceutically acceptable salt, ester, or amide thereof, wherein:

A is a 5- or 6-membered heteroaryl ring or a 6-membered aryl ring;

R 1 is —SO 2 R 10 ;

R 2 is hydrogen, or alkyl;

R 3 is aryl, heteroaryl, bicyclic heteroaryl, or —C(O)R 12 ;

R 4 is —R 14 —R 15 ;

R 5 is hydrogen, halo, aryl, heteroaryl, bicyclic heteroaryl, —R 23 —R 24 , or —R 23 —C(O)—R 24 ;

R 10 is alkyl, —N═CHN(CH 3 ) 2 , or —NR 11a R 11b ;

R 11a and R 11b are independently hydrogen or alkyl; or R 11a and R 11b taken together with the nitrogen atom to which each is attached form a 4-, 5-, or 6-membered heterocycle;

R 12 is hydrogen, alkyl, aryl, heterocycle, heteroarylalkyl, —OR 13 or —NR 16 R 17 ,

R 13 is hydrogen, alkyl or arylalkyl;

R 14 is aryl;

R 15 is aryl, heteroaryl, heterocycle or —R 21 —R 22 ;

R 16 and R 17 are independently hydrogen, alkyl, alkoxy, alkoxyalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, hydroxyalkyl or R 18 R 19 N-alkyl-;

R 18 and R 19 are independently hydrogen or alkyl;

R 21 is aryl or heteroaryl;

R 22 is arylalkyl;

R 23 is aryl; and

R 24 is heteroaryl or heterocycle.

2. The compound of claim 1 , wherein

A is phenyl; and

R 2 is alkyl.

3. The compound of claim 1 , wherein

A is phenyl; and

R 2 is methyl.

4. The compound of claim 1 , wherein

A is phenyl;

R 2 is methyl; and

R 1 is —SO 2 alkyl or —SO 2 NH 2 .

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

5-biphenyl-4-yl-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4′-chloro-biphenyl-4-yl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4′-methoxy-biphenyl-4-yl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(3′,5′-difluoro-biphenyl-4-yl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(3′-cyano-biphenyl-4-yl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-furan-3-yl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

2-methyl-1-(4-sulfamoyl-phenyl)-5-(4-thiophen-3-yl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

2-methyl-5-(4-pyridin-4-yl-phenyl)-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

1-(3-methanesulfanyl-phenyl)-2-methyl-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester;

5-[4-(1-benzyl-1H-pyrazol-4-yl)-phenyl]-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

1-(3-methanesulfonyl-phenyl)-2-methyl-5-(4-pyridin-4-yl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-[4-(5-cyano-pyridin-3-yl)-phenyl]-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4′-chloro-biphenyl-4-yl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

1-(3-methansulfonyl-phenyl)-5-(4′-methoxy-biphenyl-4-yl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4′-cyano-biphenyl-4-yl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester; and

1-(3-methanesulfonyl-phenyl)-2-methyl-5-(4-morpholin-4-yl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester.

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

7. A compound of the formula (I):

or a pharmaceutically acceptable salt, ester, or amide thereof, wherein:

A is a 5- or 6-membered heteroaryl ring or a 6-membered aryl ring;

R 1 is —SO 2 R 10 ;

R 2 is hydrogen, or alkyl;

R 3 is —C(O)R 12 ;

R 4 is aryl;

R 5 is hydrogen, halo, aryl, heteroaryl, bicyclic heteroaryl, —R 23 —R 24 , or —R 23 —C(O)—R 24 ;

R 10 is alkyl, —N═CHN(CH 3 ) 2 , or —NR 11a R 11b ;

R 11a and R 11b are independently hydrogen or alkyl; or R 11a and R 11b taken together with the nitrogen atom to which each is attached form a 4-, 5-, or 6-membered heterocycle;

R 12 is hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, cycloalkyl, aryl, heterocycle, heteroarylalkyl, or —NR 16 R 17 ;

R 16 and R 17 are independently hydrogen, alkyl, alkoxy, alkoxyalkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, hydroxyalkyl or R 18 R 19 N-alkyl-;

R 18 and R 19 are independently hydrogen or alkyl;

R 23 is aryl; and

R 24 is heteroaryl or heterocycle.

8. The compound of claim 7 , wherein

A is phenyl; and

R 2 is alkyl.

9. The compound of claim 7 , wherein

A is phenyl; and

R 2 is methyl.

10. The compound of claim 7 , wherein

A is phenyl;

R 2 is methyl; and

R 1 is —SO 2 alkyl or —SO 2 NH 2 .

11. The compound of claim 7 , wherein

A is phenyl;

R 2 is methyl;

R 1 is —SO 2 alkyl or —SO 2 NH 2 ; and

R 4 is aryl, wherein aryl is optionally substituted with 1, 2, or 3 substituents selected from the group consisting of alkyl, alkylcarbonyl, alkoxy, alkylsulfonyl, cyano, halo, haloalkyl, nitro, and —NR A R B , wherein R A and R B are independently hydrogen, alkyl, alkylcarbonyl and alkylsulfonyl.

12. The compound of claim 7 , wherein the compound is selected from the group consisting of:

5-(4-chloro-phenyl)-1-[4-(dimethylaminomethylene-sulfamoyl)-phenyl]-2-methyl-1H-pyrrole-3-carboxylic acid N-methoxy-N-methyl-amide;

4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide;

4-[5-(4-chloro-phenyl)-3-isobutyryl-2-methyl-pyrrol-1-yl]-benzenesulfonamide;

4-[5-(4-chloro-phenyl)-3-cyclopropanecarbonyl-2-methyl-pyrrol-1-yl]-benzenesulfonamide;

4-[5-(4-chloro-phenyl)-2-methyl-3-(4-methyl-benzoyl)-pyrrol-1-yl]-benzenesulfonamide;

4-[3-(4-chloro-3-methyl-benzoyl)-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-benzenesulfonamide;

4-[3-(4-chloro-benzoyl)-5-(4-chloro-phenyl)-2-methyl-pyrrol-1-yl]-benzenesulfonamide;

4-[5-(4-chloro-phenyl)-3-(5-fluoro-2-methoxy-benzoyl)-2-methyl-pyrrol-1-yl]-benzenesulfonamide;

5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid methoxy-methyl amide;

1-[5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrol-3-yl]propan-1-one;

5-(4-chloro-phenyl)-1-(4-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxaldehyde;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid isopropylamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid butylamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid (2-methoxy-ethyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(3-propoxy-propyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(R)-(tetrahydro-furan-2-ylmethyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid (tetrahydro-furan-3-ylmethyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid cyclobutylamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid dimethylamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl-methyl-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid isopropyl-methyl-amide;

4-[5-(4-chloro-phenyl)-2-methyl-3-(pyrrolidine-1-carbonyl)-pyrrol-1-yl]-benzenesulfonamide;

4-[5-(4-chloro-phenyl)-2-methyl-3-(piperidine-1-carbonyl)-pyrrol-1-yl]-benzene sulfonamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(2-methoxy-ethyl)-methyl-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-bis-(2-methoxy-ethyl)-amide;

4-[5-(4-chloro-phenyl)-2-methyl-3-(morpholine-4-carbonyl)-pyrrol-1-yl]-benzenesulfonamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid benzylamide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid (pyridin-3-ylmethyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid (2-dimethylamino-ethyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(3-dimethylamino-propyl)-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(2-hydroxy-ethyl)-propyl-amide;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid-(3-hydroxy-propyl)-amide;

N-acetyl-4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide

N-acetyl-4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide-N-sodium salt;

4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-N-propionyl-benzenesulfonamide; and

4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-N-propionyl-benzenesulfonamide-N-sodium salt.

13. A compound selected from the group consisting of:

ethyl 5-(4-bromophenyl)-2-methyl-1-[3-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxylate;

2-methyl-5-(4-pentyl-phenyl)-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-1-(4-dimethylsulfamoyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-methyl-1-[3-(pyrrolidine-1-sulfonyl)-phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester;

ethyl 5-(4-chlorophenyl)-2-methyl-1-[3-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrrole-3-carboxylate;

ethyl 5-(4-chlorophenyl)-2-methyl-1-(3-(methylsulfonyl)phenyl)-1H-pyrrole-3-carboxylate;

5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid;

5-(4-chloro-phenyl)-1-(3-ethanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid ethyl ester;

1-(3-ethanesulfonyl-phenyl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester;

2-methyl-5-phenyl-1-[3-(propane-2-sulfonyl)-phenyl]-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-2-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-(4-fluoro-phenyl)-1-(3-methanesulfonyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-(2-fluoro-phenyl)-1-(3-methanesulfonyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-ethyl-1-(3-methanesulfonyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid benzyl ester;

5-(4-chloro-phenyl)-4-iodo-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(4-hydroxymethyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-methyl-4-phenyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

4-(3-amino-phenyl)-5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-hydroxy-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-methoxy-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

4,5-bis-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-cyano-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(4-cyano-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

4-(3-acetyl-phenyl)-5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

4-benzo[1,3]dioxol-5-yl-5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3,5-dichloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-furan-3-yl-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-4-thiophen-3-yl-1H-pyrrole-3-carboxylic acid ethyl ester;

4-benzofuran-2-yl-5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-methyl-4-(3-nitro-phenyl)-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-2-methyl-4-naphthalen-2-yl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(4-methanesulfonyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(1H-indol-4-yl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-dimethylamino-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

4-(4-acetylamino-phenyl)-5-(4-chloro-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(4-methanesulfonylamino-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(3-dimethylcarbamoyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester;

5-(4-chloro-phenyl)-4-(4-cyanomethyl-phenyl)-2-methyl-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester; and

5-(4-chloro-phenyl)-2-methyl-4-[3-(4-methyl-piperazine-1-carbonyl)-phenyl]-1-(4-sulfamoyl-phenyl)-1H-pyrrole-3-carboxylic acid ethyl ester.