Oxazolidin-2-one and thiazolidin-2-one derivatives for use as EP

1. A compound having the structural formula I:

or a pharmaceutically acceptable salt thereof, wherein,

X is S;

Y 1 is

1) CH 2 CH 2 , or

2) CHCH;

Y is C(O) or CH(OH);

A and W are independently selected from the group consisting of

1) a bond, and

2) C 1-6 alkylene, unsubstituted or substituted with 1, 2, 3, or 4 halogen atoms;

Z is

4) CH 2 ,

5) HC═CH, or

6) C≡C;

R 1 is

COR 5 ,

OH,

(CH 2 ) 1-3 CO 2 R 6 ,

(CH 2 ) 0-4 SO 3 R 6 ,

CF 2 SO 2 NH 2 ,

SO 2 NH 2 ,

SO 2 NHCOR 8 ,

PO(OH) 2 ,

C 1-4 alkoxy,

hydroxymethylketone,

(CH 2 ) 0-4 heterocyclyl, wherein heterocyclyl is unsubstituted or substituted with 1 to 3 groups of R 8 , or

tetrazole;

R 2 is

1) C 1-6 alkyl, provided that R 2 is not n-pentyl or butyl,

2) (CH 2 ) 0-8 C 6-10 aryl,

3) (CH 2 ) 0-8 C 5-10 heteroaryl,

4) (CH 2 ) 0-8 C 3-10 heterocycloalkyl,

5) (CH 2 ) 0-8 C 3-8 cycloalkyl,

6) O—C 1-10 alkyl,

7) O—C 6-10 alkyl,

8) O—C 5-10 heteroaryl,

9) O—C 5-10 heterocycloalkyl, or

10) O—C 3-10 cycloalkyl,

wherein aryl, heteroaryl, heterocycloalkyl, and cycloalkyl are unsubstituted or substituted with 1–3 groups of R b ;

R 3 and R 4 are independently selected from the group consisting of

1) hydrogen,

2) halogen, and

3) C 1-6 alkyl, or

R 3 and R 4 , together with the carbon atom to which they are attached, form a C 3-7 cycloalkyl ring;

R 5 is

1) hydrogen,

2) OH,

3) CH 2 OH,

4) C 1-6 alkoxy,

5) NHPO 2 R 6 ,

6) NHR 9 ,

7) NHSO 2 R 8 , or

8) NR 6 R 7 ;

R 6 and R 7 are independently selected from the group consisting of hydrogen and C 1-6 alkyl;

R 8 is selected from the group consisting of hydrogen, C 6-10 aryl, and C 1-4 alkyl;

R 9 is acyl or sulfonyl; and

R a and R b are independently selected from the group consisting of

1) C 1-6 alkoxy,

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

a) C 1-6 alkoxy,

b) C 1-6 alkylthio,

c) CN,

d) OH, or

e) CF 3 ,

3) CF 3 ,

4) nitro,

5) amino,

6) cyano,

7) C 1-6 alkylamino,

8) halogen

9) OR c ,

10) OCH 2 R c , and

11) CH 2 OR c ;

R c is

1) C 6-10 aryl,

2) C 5-10 heteroaryl,

3) C 3-10 heterocycloalkyl, or

4) C 3-8 cycloalkyl.

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

1) cyclohexyl,

2) unsubstituted aryl, or

3) aryl substituted with

a) unsubstituted C 1-6 alkyl,

b) C 1-6 alkyl substituted with C 1-6 alkoxy

c) halogen, or

d) CF 3 .

3. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is tetrazole or COR 5 , wherein R 5 is CH 2 OH or OH.

4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein A is a bond, (CH 2 ) 1-4 , or (CH 2 ) 1-5 CF 2 , and W is a bond or (CH 2 ) 1-6 .

5. A compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein Z is

1) CH 2 ,

2) CH═CH,

3) C≡C,

R 3 and R 4 are independently selected from the group consisting of hydrogen and F, or R 3 and R 4 , together with the carbon atom to which they are attached, form a cyclopropyl or cyclohexyl ring.

6. A compound of claim 5 selected from the group consisting of

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-thiazolidin-3-yl}heptanoic acid,

7-{4-[(1E)-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-thiazolidin-3-yl}heptanoic acid,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-[(1E)-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-[(1E)-3-hydroxy-3-(1-phenylcyclopropyl)prop-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-(3-hydroxy-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-(4,4-difluoro-3-hydroxy-4]phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

7-(4-{(1E)-4,4-difluoro-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-2-oxo-1,3-thiazolidin-3-yl)heptanoic acid,

4-{(1E)-4,4-difluoro-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-[(1E)-4-cyclohexyl-4,4-difluoro-3-hydroxybut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-[(1E)-4-cyclohexyl-3-hydroxybut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-(4,4-difluoro-3-oxo-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-(3-oxo-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-(7-hydroxy-6-oxoheptyl)-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(2E)-6-(1H-tetraazol-5-yl)hex-2-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(3E)-6-(1H-tetraazol-5-yl)hex-3-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(4E)-6-(1H-tetraazol-5-yl)hex-2-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(2Z)-6-(1H-tetraazol-5-yl)hex-2-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(3Z)-6-(1H-tetraazol-5-yl)hex-3-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(4Z)-6-(1-tetraazol-5-yl)hex-4-enyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-4-ynyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-2-ynyl]-1,3-thiazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-3-ynyl]-1,3-thiazolidin-2-one,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-yl]-2-oxo-1,3-thiazolidin-3-yl)}-2,2-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-thiazolidin-3-yl}-4,4-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-thiazolidin-3-yl}-5,5-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-thiazolidin-3-yl}-6,6-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}heptanoic acid,

7-{4-[(1E)-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}heptanoic acid,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-[(1E)-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-[(1E)-3-hydroxy-3-(1-phenylcyclopropyl)prop-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-(3-hydroxy-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-(4,4-difluoro-3-hydroxy-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

7-(4-{(1E)-4,4-difluoro-3-hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-2-oxo-1,3-oxazolidin-3-yl)heptanoic acid,

4-{(1E)-4,4-difluoro-3-hydroxy-4-[3-methoxymethyl)phenyl]but-1-enyl}-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-[(1E)-4-cyclohexyl-4,4-difluoro-3-hydroxybut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-[(1E)-4-cyclohexyl-3-hydroxybut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-(4,4-difluoro-3-oxo-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-(3-oxo-4-phenylbutyl)-3-[6-(1H-tetraazol-5-yl)hexyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-(7-hydroxy-6-oxoheptyl)-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(2E)-6-(1H-tetraazol-5-yl)hex-2-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(3E)-6-(1H-tetraazol-5-yl)hex-3-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(4E)-6-(1H-tetraazol-5-yl)hex-4-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(2Z)-6-(1H-tetraazol-5-yl)hex-2-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(3Z)-6-(1H-tetraazol-5-yl)hex-3-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[(4Z)-6-(1H-tetraazol-5-yl)hex-4-enyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-4-ynyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-2-ynyl]-1,3-oxazolidin-2-one,

4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-3-[6-(1H-tetraazol-5-yl)hex-3-ynyl]-1,3-oxazolidin-2-one,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}-2,2-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}-4,4-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}-5,5-difluoroheptanoic acid,

7-{4-[(1E)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-2-oxo-1,3-oxazolidin-3-yl}-6,6-difluoroheptanoic acid, and

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition which is comprised of a compound in accordance with claim 1 and a pharmaceutically acceptable carrier.