Quinolinones as prostaglandin receptor ligands

1. A compound of Formula B

or a pharmaceutically acceptable salt, hydrate, ester or tautomer thereof, wherein:

X is selected from a bond, O or S(O)k, wherein k is 0, 1 or 2,

R 1 is selected from the group consisting of:

(1) hydrogen,

(2) halo,

(3) hydroxy,

(4) C 1-6 alkyl,

(5) C 1-6 alkenyl,

(6) C 1-6 alkoxy,

(7) C 1-6 alkyl-S(O) m —, wherein m is 0, 1, 2 or 3

(8) C 1-6 alkyl-C(O)—

(7) C 1-6 alkoxy-C(O)—

(9) C 1-6 alkyl-C(O)—O—

(10) aryl,

(11) aralkyl,

(12) aryloxy,

(13) aralkoxy,

(14) arylthio,

(15) aroyl,

(16) aroyloxy and

wherein the alkyl , alkenyl and aryl portions of items (4)-(16) above are optionally substituted from one up to the maximum number of substituable positions with a member independently selected from the group consisting of: halo, heterocycle, C 1-6 alkoxy, C 1-6 alkyl-S(O) k —, C 1-6 alkyl-C(O)—, C 1-6 alkoxy-C(O), C 1-6 alkyl-C(O)—O, carboxy, hydroxy and aralkoxy, the alkyl portions of said C 1-6 alkoxy, C 1-6 alkyl-S(O) k —, C 1-6 alkyl-C(O)—, C 1-6 alkoxy-C(O) and C 1-6 alkyl-C(O)—O groups optionally substituted with 1-3 substituents independently selected from: halo and hydroxy,

said aryl portions of items (10)-(16) above further optionally substituted from one up to the maximum number of substituable positions with C 1-6 alkyl, optionally substituted with 1-3 substituents independently selected from the group consisting of: halo and hydroxy;

R 3 is selected from the group consisting of:

(1) C 1-6 alkyl, C 2-6 alkenyl or C 3-6 alkynyl, each optionally substituted with 1-3 halo groups.

(2) aryl, optionally substituted with 1-3 halo groups,

(3) aralkyl, optionally substituted with a substituent independently selected from the group consisting of: C 1-6 alkylsulfonyl and halo,

R 4 , R 5 , R 6 and R 7 are each independently selected from the group consisting of:

(1) hydrogen,

(2) halo, and

(3) C 1-6 alkyl, optionally substituted with 1-3 halo groups,

R 8 is selected from the group consisting of H, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkyl-C(O)—and aryl, the aryl, alkyl and alkenyl portions are optionally substituted with 1-3 halo groups,

R 9 and R 10 are independently selected from the group consisting of:

(1) halo,

(2) C 1-6 alkyl,

(3) C 1-6 alkenyl,

(4) C 1-6 alkoxy,

(5) C 1-6 alkyl-S(O) k —, wherein k is 0, 1 or 2,

(6) C 1-6 alkyl-C(O)—,

(7) C 1-6 alkoxy-C(O),

(8) C 1-6 alkyl-C(O)—O—,

(9) carboxy,

(10) hydroxy, and

(11) N(R8)2,

wherein the alkyl and alkenyl portions of items (2)-(8) above are optionally substituted from one up to the maximum number of substituable positions with a member independently selected from the group consisting of: halo, heterocycle, C 1-6 alkoxy, C 1-6 alkyl-S(O) k —, C 1-6 alkyl-C(O)—, C 1-6 alkoxy-C(O)—, C 1-6 alkyl-C(O)—O—, aralkoxy, carboxy and hydroxy, the alkyl portions of said C 1-6 alkoxy, C 1-6 alkyl-S(O) k —, C 1-6 alkyl-C(O)—, C 1-6 alkoxy-C(O) and C 1-6 alkyl-C(O)—O groups optionally substituted with 1-3 substituents independently selected from halo and hydroxy.

2. The compound according to claim 1 wherein:

X is selected from a bond, O or S(O)k, wherein k is 0, 1 or 2,

R 1 is selected from the group consisting of:

(1) halo,

(2) hydroxy,

(3) C 1-6 alkyl,

(4) C 1-6 alkoxy, and

(5) N(R 8 ) 2 , wherein R 8 is H or C 1-4 alkyl,

wherein the alkyl portions of items (3)-(4) above are optionally substituted with 1-3 halo groups,

R 3 is C 1-6 alkyl or C 2-4 alkenyl, each optionally substituted with 1-3 halo groups.

R 4 , R 5 , R 6 , R 7 and R 9 are each H, and

R 10 is H or halo.

3. The compound according to claim 2 selected from the group consisting of:

(1) 3-{4-[(4-chlorophenyl)thio]benzyl}-4-hydroxy-1-methylquinolin-2(1H)-one;

(2) 1-allyl-3-{4-[(4-chlorophenyl)thio]benzyl}-4-hydroxyquinolin-2(1H)-one;

(3) 1-allyl-4-amino-3-{4-[(4-chlorophenyl)thio]benzyl}quinolin-2(1H)-one;

(4) 3-[(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)methyl]-4-hydroxy-1-methylquinolin-2(1H)-one;

(5) 1-allyl-3-[(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)methyl]-4-hydroxyquinolin-2(1H)-one;

(6) 4-amino-3-[(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)methyl]-1-methylquinolin-2(1H)-one;

(7) 3-[(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)methyl]-4-(difluoromethoxy)-1-methylquinolin-2(1H)-one; and

(8) 3-{4-[(4-chlorophenyl)sulfonyl]benzyl}-4-hydroxy-1-methylquinolin-2(1H)-one.

4. 4-amino-3-[(3′-chloro-4′-fluoro-1,1′-biphenyl-4-yl)methyl]-1-methylquinolin-2(1H)-one; or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

6. A pharmaceutical composition comprising the compound of claim 4 and a pharmaceutically acceptable carrier.