Aryl acylsulfonamides as BLT1 antagonists

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof; wherein

A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl and halogen;

B 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 alkyl and halogen;

X is selected from the group consisting of:

(1) —C(O)NHSO 2 CF 3 ,

(2) —C(O)NHSO 2 CH 2 CF 3 ,

(3) —C(O)NHSO 2 CHF 2 ,

(4) —C(O)NHSO 2 C 1-6 alkyl,

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

(6) —C(O)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) hydrogen,

(2) —C 1-6 alkyl, and

(3) phenyl,

wherein alkyl and phenyl 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 X is selected from the group consisting of:

(1) —C(O)NHSO 2 CH 2 CF 3 ,

(2) —C(O)NHSO 2 CHF 2 ,

(3) —C(O)NHSO 2 C 1-6 alkyl,

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

(5) —C(O)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; or a pharmaceutically acceptable salt thereof.

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

(1) —C(O)NHSO 2 CF 3 ,

(2) —C(O)NHSO 2 C 1-6 alkyl,

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

(4) —C(O)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; or a pharmaceutically acceptable salt thereof.

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

(1) —C(O)NHSO 2 C 1-6 alkyl, and

(2) —C(O)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; or a pharmaceutically acceptable salt thereof.

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

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

7. The compound according to claim 1 wherein A is selected from the group consisting of: pyridine, oxazole, thiazole, thiadiazole, and pyrazole, wherein pyridine, oxazole, thiazole, thiadiazole, and pyrazole are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein A is oxazole, wherein oxazole is unsubstituted or substituted with 1-3 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 selected from the group consisting of: pyridine, thiazole, thiadiazole, and pyrazole, wherein pyridine, thiazole, thiadiazole, and pyrazole are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl; or a pharmaceutically acceptable salt thereof.

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

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

12. 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.

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

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

15. 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;

B is aryl, wherein aryl 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) —C(O)NHSO 2 CF 3 ,

(2) —C(O)NHSO 2 C 1-6 alkyl,

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

(4) —C(O)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) hydrogen,

(2) —C 1-6 alkyl, and

(3) phenyl,

wherein alkyl and phenyl are unsubstituted or substituted with 1-4 substituents independently selected from C 1-6 alkyl; and

R a and R b are 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

A is oxazole, wherein oxazole is unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl and halogen;

B is phenyl;

X is selected from the group consisting of:

(1) —C(O)NHSO 2 C 1-6 alkyl, and

(2) —C(O)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 phenyl, wherein phenyl 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.

17. The compound according to claim 1 wherein

A is selected from the group consisting of: pyridine, thiazole, thiadiazole, and pyrazole, wherein pyridine, thiazole, thiadiazole, and pyrazole are unsubstituted or substituted with 1-3 substituents independently selected from C 1-6 alkyl;

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

X is selected from the group consisting of:

(1) —C(O)NHSO 2 CF 3 ,

(2) —C(O)NHSO 2 C 1-6 alkyl,

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

(4) —C(O)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 hydrogen; and

R a and R b are selected from the group consisting of: hydrogen, and C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof.

18. A compound from:

(1) 4-Fluoro-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((trifluoro-methyl)sulfonyl)benzamide;

(2) 4-Fluoro-2-((3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((trifluoro-methyl)sulfonyl)benzamide;

(3) 4-Fluoro-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-(methyl-sulfonyl)benzamide;

(4) 4-Fluoro-2-(3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-(methyl-sulfonyl)benzamide;

(5) N-(Cyclopropylsulfonyl)-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(6) N-(Cyclopropylsulfonyl)-2-(3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(7) 2-((3S,4R)-4-Hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((1-methylcyclo-propyl)sulfonyl)benzamide;

(8) 2-((3R,4S)-4-Hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((1-methylcyclo-propyl)sulfonyl)benzamide;

(9) 4-Fluoro-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((1-methyl-cyclopropyl)sulfonyl)benzamide;

(10) 4-Fluoro-2-((3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-((1-methyl-cyclopropyl)sulfonyl)benzamide;

(11) N-(tert-Butylsulfonyl)-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(12) N-(tert-Butylsulfonyl)-2-((3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(13) N-(tert-Butylsulfonyl)-4-fluoro-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(14) N-(tert-Butylsulfonyl)-4-fluoro-2-(3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(15) N-(Cyclopropylsulfonyl)-4-fluoro-2-((3S,4R)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(16) N-(Cyclopropylsulfonyl)-4-fluoro-2-(3R,4S)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(17) 2-((3,4-trans)-4-Hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-(isobutylsulfonyl)-benzamide;

(18) N-((Cyclopropylmethyl)sulfonyl)-2-((3,4-trans)-4-hydroxy-3-(pyridin-2-ylmethyl)-chroman-7-yl)benzamide;

(19) N-(Cyclopentylsulfonyl)-2-((3,4-trans)-4-hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)benzamide;

(20) 2-((3,4-trans)-4-Hydroxy-3-(pyridin-2-ylmethyl)chroman-7-yl)-N-(neopentylsulfonyl)-benzamide;

(21) 2-((3S,4R)-3-Benzyl-4-hydroxychroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)-benzamide;

(22) 2-((3R,4S)-3-Benzyl-4-hydroxychroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)-benzamide;

(23) 2-((3S,4R)-3-Benzyl-4-hydroxychroman-7-yl)-N-(cyclopropylsulfonyl)benzamide;

(24) 2-((3R,4S)-3-Benzyl-4-hydroxychroman-7-yl)-N-(cyclopropylsulfonyl)benzamide;

(25) 2-(Rac-trans)-4-Hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)-N-((1-methyl-cyclopropyl)sulfonyl)benzamide;

(26) 4R)-4-Hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)-N-((1-methylcyclopropyl)-sulfonyl)benzamide;

(27) 2-(3R,4S)-4-Hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)-N-((1-methylcyclopropyl)-sulfonyl)benzamide;

(28) 2-(Rac-trans)-4-Hydroxy-3-((1-methyl-1H-pyrazol-5-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(29) 2-((Rac-trans)-4-Hydroxy-3-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(30) 2-((Rac-trans)-3-((1-ethyl-1H-pyrazol-5-yl)methyl)-4-hydroxychroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(31) N-(tert-Butylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)chroman-7-yl)benzamide;

(32) N-(tert-Butylsulfonyl)-2-((rac-trans)-4-hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)benzamide;

(33) N-(tert-Butylsulfonyl)-2-((3S,4R)-4-hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)benzamide;

(34) N-(tert-Butylsulfonyl)-2-(3R,4S)-4-hydroxy-3-(thiazol-4-ylmethyl)chroman-7-yl)benzamide;

(35) N-(tert-Butylsulfonyl)-2-((rac-trans)-4-hydroxy-3-((1-methyl-1H-pyrazol-5-yl)methyl)chroman-7-yl)benzamide;

(36) N-(tert-Butylsulfonyl)-2-((rac-trans)-3-((1-ethyl-1H-pyrazol-5-yl)methyl)-4-hydroxychroman-7-yl)benzamide;

(37) N-(tert-Butylsulfonyl)-2-((3S,4R)-3-((1-ethyl-1H-pyrazol-5-yl)methyl)-4-hydroxychroman-7-yl)benzamide;

(38) N-(tert-Butylsulfonyl)-2-((3R,4S)-3-((1-ethyl-1H-pyrazol-5-yl)methyl)-4-hydroxychroman-7-yl)benzamide;

(39) 2-((Rac-cis)-3-([1,1′-Biphenyl]-4-ylmethyl)-4-hydroxychroman-7-yl)-4-fluoro-N-((trifluoromethyl)sulfonyl)benzamide;

(40) 2-((Rac-trans)-3-([1,1′-Biphenyl]-4-ylmethyl)-4-hydroxychroman-7-yl)-4-fluoro-N-((trifluoromethyl)sulfonyl)benzamide;

(41) 2-((3R,4S)-3-([1,1′-Biphenyl]-4-ylmethyl)-4-hydroxychroman-7-yl)-4-fluoro-N-((trifluoromethyl)sulfonyl)benzamide;

(42) 2-((3S,4R)-3-([1,1′-Biphenyl]-4-ylmethyl)-4-hydroxychroman-7-yl)-4-fluoro-N-((trifluoromethyl)sulfonyl)benzamide;

(43) 2-(Rac-trans)-4-hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(44) 2-((3R,4S or 3S,4R)-4-Hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(45) 2-((3S,4R or 3R,4S)-4-hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

(46) 2-(Rac-trans)-4-Hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide

(47) N-(tert-Butylsulfonyl)-2-(3R,4S)-4-hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)benzamide;

(48) N-(tert-Butylsulfonyl)-2-((3S,4R)-4-hydroxy-3-((2-phenyloxazol-4-yl)methyl)chroman-7-yl)benzamide;

(49) 2-((3,4-trans)-4-Hydroxy-3-((R)-1-(pyridin-2-yl)ethyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide; and

(50) 2-((3,4-trans)-4-Hydroxy-3-((S)-1-(pyridin-2-yl)ethyl)chroman-7-yl)-N-((1-methylcyclopropyl)sulfonyl)benzamide;

or a pharmaceutically acceptable salt thereof.

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

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