Aryl sulfonamides as BLT1 antagonists

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

A is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein aryl and heteroaryl are unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alky, C 3-6 cycloalkyl, and halogen;

B is selected from the group consisting of:

(1) aryl, and

(2) heteroaryl,

wherein aryl is unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl and halogen, and wherein heteroaryl is unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl and halogen;

X is selected from the group consisting of:

(1) —NHSO 2 CF 3 ,

(2) —NHSO 2 CH 2 CF 3 ,

(3) —NHSO 2 CHF 2 ,

(4) —NHSO 2 C 1-6 alkyl,

(5) —NHSO 2 CH 2 C 3-6 cycloalkyl, and

(6) —NHSO 2 C 3-6 cycloalkyl,

wherein alkyl and cycloalkyl are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl;

Z is selected from the group consisting of:

(1) heteroaryl,

(2) C 2-6 cycloheteroalkyl, and

(3) C 3-6 cycloalkyl,

wherein heteroaryl, cycloheteroalkyl and cycloalkyl are unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl;

R a is selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) C 1-6 alkyl; and

R b is selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) C 1-6 alkyl.

2. The compound according to claim 1 wherein Z is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 wherein Z is selected from the group consisting of:

(1) pyridine,

(2) pyrazole, and

(3) thiazole,

wherein pyridine, pyrazole, and thiazole are independently unsubstituted or substituted with 1-4 substituents independently selected from selected from C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein Z is thiazole; or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 wherein X is selected from the group consisting of:

(1) —NHSO 2 CF 3 ,

(2) —NHSO 2 CH 2 CF 3 ,

(3) —NHSO 2 CHF 2 , and

(4) —NHSO 2 C 1-4 alkyl;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 wherein X is —NHSO 2 CF 3 ; or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 wherein A is selected from the group consisting of:

(1) phenyl, and

(2) heteroaryl,

wherein phenyl and heteroaryl are unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl and halogen; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein A is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl and halogen; or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 wherein A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl and halogen; or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 wherein A is selected from the group consisting of:

(1) pyridine, and

(2) triazole,

wherein pyridine and triazole are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl and halogen; or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 wherein A is pyridine; or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 wherein B is selected from the group consisting of:

(1) phenyl, and

(2) pyridine,

wherein phenyl and pyridine are unsubstituted or substituted with 1-4 substituents independently selected from halogen; or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 wherein B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from halogen; or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 wherein B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from F; or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 wherein R a and R b are independently selected from the group consisting of: hydrogen, and C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 wherein R a and R b are hydrogen; or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 wherein

A is selected from the group consisting of:

(1) pyridine, and

(2) triazole,

wherein pyridine and triazole are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl and halogen;

B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from halogen;

X is —NHSO 2 CF 3 ;

Z is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl; and

R a and R b are hydrogen;

or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1 wherein

A is pyridine;

B is phenyl, wherein phenyl is unsubstituted or substituted with 1-4 substituents independently selected from F;

X is —NHSO 2 CF 3 ;

Z is thiazole, wherein thiazole is unsubstituted or substituted with 1-2 substituents independently selected from C 1-6 alkyl; and

R a and R b are hydrogen;

or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 1 selected from:

(1) 1,1,1-Trifluoro-N-(2-((3R,4S)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(2) 1,1,1-Trifluoro-N-(2-((3S,4R)-4-hydroxy-3-((5-(thiazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(3) 1,1,1-Trifluoro-N-(2-((3S,4R)-4-hydroxy-3-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(4) 1,1,1-Trifluoro-N-(2-((3R,4S)-4-hydroxy-3-((5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(5) 1,1,1-Trifluoro-N-(2-((3,4-trans)-4-hydroxy-3-((5-(1-methyl-1H-pyrazol-5-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(6) 1,1,1-Trifluoro-N-(2-((3R,4S)-4-hydroxy-3-((5-(5-methylthiazol-2-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(7) 1,1,1-Trifluoro-N-(2-((3S,4R)-4-hydroxy-3-((5-(5-methylthiazol-2-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(8) 1,1,1-trifluoro-N-{4-fluoro-2-[(rac-trans) 4-hydroxy-3-{[5-(1,3-thiazol-5-yl)pyridin-2-yl]methyl}-3,4-dihydro-2H-chromen-7-yl]phenyl}methanesulfonamide;

(9) 1,1,1-Trifluoro-N-(2-((3,4-trans)-4-hydroxy-3-((5-(thiazol-4-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(10) 1,1,1-Trifluoro-N-(2-((3,4-trans)-4-hydroxy-3-((5-(thiazol-2-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(11) 1,1,1-Trifluoro-N-(2-((3,4-trans)-4-hydroxy-3-((5-(thiazol-2-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(12) 1,1,1-Trifluoro-N-(2-((3,4-trans)-4-hydroxy-3-((5-(thiazol-4-yl)pyridin-2-yl)methyl)chroman-7-yl)phenyl)methanesulfonamide;

(13) 1,1,1-trifluoro-N-{4-fluoro-2-[(3S,4R)-4-hydroxy-3-{[5-(1,3-thiazol-5-yl)pyridin-2-yl]methyl}-3,4-dihydro-2H-chromen-7-yl]phenyl}methanesulfonamide; and

(14) 1,1,1-trifluoro-N-{4-fluoro-2-[(3R,4S)-4-hydroxy-3-{[5-(1,3-thiazol-5-yl)pyridin-2-yl]methyl}-3,4-dihydro-2H-chromen-7-yl]phenyl}methanesulfonamide;

or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

21. A method of treating type 2 diabetes mellitus in a patient in need of treatment comprising administration to the patient of a therapeutically effective amount of a compound of claim 1 , of a pharmaceutically acceptable salt thereof.