PYRROLIDINONE ANILINES AS PROGESTERONE RECEPTOR MODULATORS

1 . A compound represented by the following formula:

or a pharmaceutically acceptable salt thereof;

where X is H, halo, or CF 3 ;

R 1 is H, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxycarbonyl-(CH 2 ) o —, C 1 -C 6 -alkylcarbonyloxy-(CH 2 ) p —, C 1 -C 6 -alkoxy-C 1 -C 5 -alkyl, hydroxy-C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, heterocycloalkyl-(CH 2 ) m —, C 1 -C 6 -alkyl-heterocycloalkyl-(CH 2 ) m —, —CH 2 CF 3 , C 1 -C 6 -alkylcarbonyl-(CH 2 ) o —, C 3 -C 4 -alkenyl, naphthyl, —(CH 2 ) m -heteroaryl-(R 3 ) n , or —(CH 2 ) m -phenyl-(R 3′ ) n ; and

R 2 is C 1 -C 5 -alkyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkoxycarbonyl-C 1 -C 5 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 5 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, heterocycloalkyl, C 1 -C 6 -alkyl-heterocycloalkyl, C 2 -C 4 -alkenyl, naphthyl, heteroaryl-(R 3 ) n , or phenyl-(R 3′ ) n ;

where m is an integer from 0 to 6; n is an integer from 0 to 5; o is an integer from 1 to 6; p is an integer from 2 to 6; where each R 3 is independently C 1 -C 6 -alkyl, F, Cl, Br, CF 3 , C 1 -C 6 -alkoxy, dimethylamino, C 2 -C 4 -alkenyl, oxo, or CN, or where 2 of the R 3 groups, together with the heteroaryl ring to which they are attached form a fused ring;

and where each R 3′ is independently C 1 -C 6 -alkyl, F, Cl, Br, CF 3 , C 1 -C 6 -alkoxy, dimethylamino, C 2 -C 4 -alkenyl, or CN, or where 2 of the R 3′ groups, together with the phenyl ring to which they are attached form a fused bicyclic ring.

2 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1 -C 6 -alkyl or benzyl; R 2 is phenyl-(R 3′ ) n , where n is an integer from 0 to 2; and X is chloro.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl, ethyl, or isopropyl; each R 3′ is independently chloro, fluoro, trifluoromethyl, or methyl; and n=0, 1, 2, or 3.

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, which compound is represented by the following structure:

or a pharmaceutically acceptable salt thereof, where n is 0, 1, or 2; R 1 is C 1 -C 6 -alkyl or benzyl; and each R 3′ is independently chloro, fluoro, trifluoromethyl, or methyl.

5 . A compound selected from the group consisting of:

2-chloro-4-{[(3S)-1-methyl-5-oxo-3-pyrrolidinyl][(2-methylphenyl)methyl]amino}benzonitrile;

2-chloro-4-{[(2-fluorophenyl)methyl][(3S)-1-methyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(2,4-difluorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(2,3-difluorophenyl)methyl][(3S)-1-methyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-[[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl](phenylmethyl)amino]benzonitrile;

2-chloro-4-{[(2,5-dichlorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(2-chloro-5-fluorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(2-chlorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl][(2-methylphenyl)methyl]amino}benzonitrile;

2-chloro-4-{[(2,3-difluoro-4-methylphenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile;

2-chloro-4-{[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl][(5-fluoro-2-methylphenyl)methyl]amino}benzonitrile;

2-chloro-4-{[(2-chlorophenyl)methyl][(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrile; and

2-chloro-4-{[(2,5-dichlorophenyl)methyl][(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

6 . A pharmaceutically acceptable salt of the compound of claim 5 .

7 . A composition that comprises a) the compound of claim 1 , or a pharmaceutically acceptable salt thereof; and b) a pharmaceutically acceptable carrier.

8 . A method comprising administering to a patient in need thereof an effective amount of the compound of claim 1 , or a pharmaceutically-acceptable salt thereof to treat endometreosis, uterine fibroids, dysmenorrhea, menorrhagia, pre-term labor, or infertility.

9 . A method comprising administering to a patient in need thereof an effective amount of the compound of claim 1 , or a pharmaceutically-acceptable salt thereof, to provide contraception or hormone therapy.

10 . A compound of claim 5 , which is 2-chloro-4-{[(2-fluorophenyl)methyl][(3S)-1-methyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

11 . A compound of claim 5 , which is 2-chloro-4-{[(2,4-difluorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

12 . A compound of claim 5 , which is 2-chloro-4-{[(2,3-difluorophenyl)methyl][(3S)-1-methyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

13 . A compound of claim 5 , which is 2-chloro-4-[[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl](phenylmethyl)amino]benzonitrile.

14 . A compound of claim 5 , which is 2-chloro-4-{[(2,5-dichlorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

15 . A compound of claim 5 , which is 2-chloro-4-{[(2-chloro-5-fluorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

16 . A compound of claim 5 , which is 2-chloro-4-{[(2-chlorophenyl)methyl][(3S)-1-ethyl-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

17 . A compound of claim 5 , which is 2-chloro-4-{[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl][(2-methylphenyl)methyl]amino}benzonitrile.

18 . A compound of claim 5 , which is 2-chloro-4-{[(3S)-1-ethyl-5-oxo-3-pyrrolidinyl][(5-fluoro-2-methylphenyl)methyl]amino}benzonitrile.

19 . A compound of claim 5 , which is 2-chloro-4-{[(2-chlorophenyl)methyl][(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrile.

20 . A compound of claim 5 , which is 2-chloro-4-{[(2,5-dichlorophenyl)methyl][(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrile.