Mineralocorticoid receptor antagonists

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein

X is O;

Y is NR 2 R 3 ;

each R 1 is independently halo, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, or OR, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

each R is independently H, C 1 -C 6 alkyl, or C 3 -C 10 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from halo, OH, C 1 -C 6 alkoxy, CF 3 , or CN;

each R a is independently H, C 1 -C 6 alkyl, or C 3 -C 10 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from C 1 -C 6 alkyl, halo, OR, CF 3 , or CN;

each R b is independently H, C 1 -C 6 alkyl, C 3 -C 0 cycloalkyl, or aryl, wherein said alkyl, cycloalkyl and aryl are optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

R 2 is H, C 1 -C 6 alkyl, CF 3 , or C 3 -C 10 cycloalkyl, where said alkyl or cycloalkyl are optionally substituted with one to three groups selected from C 1 -C 6 alkyl, halo, OR, CF 3 , or CN;

R 3 is (CR d 2 ) t -aryl, C 3 -C 10 cycloalkyl, or (CR d 2 ) t -heteroaryl, where said alkyl, aryl, cycloalkyl, or heteroaryl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, OR, halo, CF 3 , or aryl;

each R d is independently H, halo, CF 3 , or C 1 -C 6 alkyl, where said alkyl is optionally substituted with one to three halo or OR;

R 4 is isopropyl, aryl, C 3 -C 10 cycloalkyl, heteroaryl, or heterocyclyl, where said alkyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, halo, CF 3 , or OR;

m is 0, 1, 2 or 3;

p is 0, 1, or 2;

t is 0, 1 or 2; and

z is 0 or 1.

2. The compound of Formula I, according to claim 1 , wherein

each R 1 is independently halo, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, or OR, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

R 2 is H or C 1 -C 6 alkyl, where said alkyl is optionally substituted with one to three groups selected from C 1 -C 6 alkyl, halo, OR, CF 3 , or CN;

R 3 is (CR d 2 ) t -aryl, C 3 -C 10 cycloalkyl, or (CR d 2 ) t -heteroaryl, where said aryl, cycloalkyl, or heteroaryl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, OR, halo, CF 3 , or aryl;

R 4 is

1) isopropyl,

2) aryl, where aryl is selected from phenyl, indenyl, naphthyl, dihydroindenyl, or tetrahydronaphthalenyl, or

3) C 3 -C 10 cycloalkyl,

where said alkyl, aryl, or cycloalkyl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, halo, CF 3 , or OR; and

m is 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , as illustrated by structural Formula II:

or a pharmaceutically acceptable salt thereof, wherein

each R 1 is independently halo or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

each R is independently H, C 1 -C 6 alkyl, or C 3 -C 10 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from halo, OH, C 1 -C 6 alkoxy, CF 3 , or CN;

each R a is independently H or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one to three groups selected from C 1 -C 6 alkyl, halo, OR, CF 3 , or CN;

each R b is independently H or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

R 2 is H or C 1 -C 6 alkyl;

R 3 is (CR d 2 ) t -aryl, C 3 -C 10 cycloalkyl, or (CR d 2 ) t -heteroaryl, where said aryl, cycloalkyl, or heteroaryl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, OR, halo, CF 3 , or aryl;

each R d is independently H, halo, CF 3 , or C 1 -C 6 alkyl, where said alkyl is optionally substituted with one to three halo or OR;

R 4 is

1) isopropyl,

2) aryl, where aryl is selected from phenyl, indenyl, naphthyl, dihydroindenyl, or tetrahydronaphthalenyl, or

3) C 3 -C 10 cycloalkyl,

where said alkyl, aryl, or cycloalkyl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, halo, CF 3 , or OR;

m is 0 or 1;

p is 0 or 1; and

t is 0 or 1.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein

R 3 is

1) (CR d 2 ) t -phenyl,

2) C 3 -C 10 cycloalkyl, or

3) (CR d 2 ) t -heteroaryl, where heteroaryl is pyridinyl, pyrazinyl, pyrimidinyl, or indolyl,

where said phenyl, cycloalkyl, or heteroaryl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, OR, halo, CF 3 , or aryl.

5. The compound of claim 1 , as illustrated by structural Formula III:

or a pharmaceutically acceptable salt thereof, wherein

each R 1 is independently halo or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with one to three groups selected from halo, OR, CF 3 , or CN;

each R is independently H, C 1 -C 6 alkyl, or C 3 -C 10 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted with one to three groups selected from halo, OH, C 1 -C 6 alkoxy, CF 3 , or CN;

each R a is independently H or C 1 -C 6 alkyl;

each R b is independently H or C 1 -C 6 alkyl;

R 3 is

1) (CR d 2 ) t -phenyl,

2) C 3 -C 10 cycloalkyl, or

3) (CR d 2 ) t -heteroaryl, where heteroaryl is pyridinyl, pyrazinyl, pyrimidinyl, or indolyl,

where said phenyl, cycloalkyl, or heteroaryl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, OR, halo, CF 3 , or aryl;

each R d is independently H, halo, CF 3 , or C 1 -C 6 alkyl, where said alkyl is optionally substituted with one to three halo or OR;

R 4 is

1) isopropyl,

2) aryl, where aryl is selected from phenyl, dihydroindenyl, or tetrahydronaphthalenyl,

or

3) C 3 -C 6 cycloalkyl,

where said alkyl, aryl, or cycloalkyl is optionally substituted with one to four groups selected from C 1 -C 6 alkyl, halo, CF 3 , or OR;

m is 0 or 1;

p is 0 or 1; and

t is 0 or 1.

6. A compound which is

Compound

Number

CName

1

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-2,4-dioxo-3-[(1R)-1-phenylethyl]-1,3-

oxazolidine-5-carboxamide

2

(5R)-N-(3,4-Dichlorobenzyl)-5-(4-fluorobenzyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-

2,4-dioxo-1,3-oxazolidine-5-carboxamide

3

(5R)-N-(3,5-Dimethoxybenzyl)-5-(4-fluorobenzyl)-2,4-dioxo-3-[(1R)-1-

phenylethyl]-1,3-oxazolidine-5-carboxamide

4

(5R)-5-Benzyl-2,4-dioxo-N-(trans-3-phenylcyclobutyl)-3-[(1R)-1-phenylethyl]-1,3-

oxazolidine-5-carboxamide

5

5-(3-Chlorobenzyl)-N-(3,5-dimethoxybenzyl)-2,4-dioxo-3-[(1R)-1-phenylethyl]-

1,3-oxazolidine-5-carboxamide

6

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-3-(1-methylethyl)-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

7

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-2,4-dioxo-3-(1,2,3,4-

tetrahydronaphthalen-1-yl)-1,3-oxazolidine-5-carboxamide

8

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

9

(5R)-5-Benzyl-3-[(1R)-1-(4-chlorophenyl)ethyl]-N-(3,5-dimethoxybenzyl)-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

10

(5R)-5-Benzyl-3-[(1R)-1-cyclohexylethyl]-N-(3,5-dimethoxybenzyl)-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

11

(5R)-5-Benzyl-3-[(1R)-2,3-dihydro-1H-inden-1-yl]-N-(3,5-dimethoxybenzyl)-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

12

5-Benzyl-N-(4-chlorophenyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

13

(5R)-5-Benzyl-N-(3-fluorophenyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

14

(5R)-5-Benzyl-N-(4-chlorophenyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

15

(5R)-5-Benzyl-N-(4-fluorophenyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

16

(5R)-N-(4-Chlorophenyl)-3-[(1R)-1-cyclohexylethyl]-5-(4-fluorobenzyl)-2,4-dioxo-

1,3-oxazolidine-5-carboxamide

17

(5R)-5-Benzyl-3-[(1R)-1-cyclohexylethyl]-N-(3,4-dichlorobenzyl)-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

18

(5R)-5-Benzyl-N-[1-(3-chlorophenyl)-2,2,2-trifluoroethyl]-3-[(1R)-1-(4-

fluorophenyl)ethyl]-2,4-dioxo-1,3-oxazolidine-5-carboxamide

19

(5R)-5-Benzyl-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-N-phenyl-1,3-

oxazolidine-5-carboxamide

20

(5R)-5-Benzyl-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-N-pyridin-2-yl-1,3-

oxazolidine-5-carboxamide

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 , which is

Compound

Number

IUPAC Name

1

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-2,4-dioxo-3-[(1R)-1-phenylethyl]-1,3-

oxazolidine-5-carboxamide

8

(5R)-5-Benzyl-N-(3,5-dimethoxybenzyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

9

(5R)-5-Benzyl-3-[(1R)-1-(4-chlorophenyl)ethyl]-N-(3,5-dimethoxybenzyl)-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

10

(5R)-5-Benzyl-3-[(1R)-1-cyclohexylethyl]-N-(3,5-dimethoxybenzyl)-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

11

(5R)-5-Benzyl-3-[(1R)-2,3-dihydro-1H-inden-1-yl]-N-(3,5-dimethoxybenzyl)-2,4-

dioxo-1,3-oxazolidine-5-carboxamide

15

(5R)-5-Benzyl-N-(4-fluorophenyl)-3-[(1R)-1-(4-fluorophenyl)ethyl]-2,4-dioxo-1,3-

oxazolidine-5-carboxamide

18

(5R)-5-Benzyl-N-[1-(3-chlorophenyl)-2,2,2-trifluoroethyl]-3-[(1R)-1-(4-

fluorophenyl)ethyl]-2,4-dioxo-1,3-oxazolidine-5-carboxamide

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprised of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 further comprising one or more other pharmaceutically active ingredients.