Granted Patent B2

US 7,943,669 · App. 11/917,811 · Granted May 17, 2011

Abstract

Claims (164)

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is O, S, OCH 2 , or SCH 2 ;

X 1 is O or S;

R 1 is H, C 1-8 alkyl, C 2-8 alkenyl, aryl, heteroaryl, C 3-10 cycloalkyl, or a heterocyclyl, wherein each R 1 group is substituted with 0-4 R 1a ;

R 1a , at each occurrence, is S substituted with 0-1 R 1b , O substituted with 0-1 R 1b , halogen, NH 2 substituted with 0-2 R 1b , —CN, NO 2 , C 1-6 alkyl substituted with 0-3 R 1b , C 2-6 alkenyl substituted with 0-2 R 1b , C 2-6 alkynyl substituted with 0-2 R 1b , aryl substituted with 0-2 R 1b , heteroaryl substituted with 0-2 R 1b , C 3-10 cycloalkyl substituted with 0-2 R 1b , or heterocycle substituted with 0-2 R 1b ;

R 1b , at each occurrence, is S substituted with 0-1 R 1c , O substituted with 0-1 R 1c , halogen, methanesulfonyl, NH 2 substituted with 0-2 R 1c , —CN, NO 2 , C 1-6 alkyl substituted with 0-3 R 1c , C 2-6 alkenyl substituted with 0-2 R 1c , aryl substituted with 0-2 R 1c , heteroaryl substituted with 0-2 R 1c , C 3-10 cycloalkyl substituted with 0-2 R 1c , or a heterocycle substituted with 0-2 R 1c ;

R 1c , at each occurrence, is S substituted with 0-1 R 1d , O substituted with 0-1 R 1d , halogen, NH 2 substituted with 0-2 R 1d , —CN, NO 2 , C 1-6 alkyl substituted with 0-2 R 1d , C 2-6 alkenyl substituted with 0-2 R 1d , aryl substituted with 0-2 R 1d , heteroaryl substituted with 0-2 R 1d , C 3-10 cycloalkyl substituted with 0-2 R 1d , or a heterocycle substituted with 0-2 R 1d ;

R 1d , at each occurrence, is OH, SH, S, O, halogen, NH 2 , —CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, aryl, CF 3 , or OCF 3 ;

R 2 is —C≡C—R 2a or —CH═CH—R 2a ;

R 2a , at each occurrence, is S substituted with 0-1 R 2b , O substituted with 0-1 R 2b , halogen, NH 2 substituted with 0-2 R 2b , —CN, NO 2 , C 1-6 alkyl substituted with 0-2 R 2b , C 2-6 alkenyl substituted with 0-2 R 2b , aryl substituted with 0-2 R 2b , heteroaryl substituted with 0-2 R 2b , C 3-10 cycloalkyl substituted with 0-2 R 2b , or a heterocycle substituted with 0-2;

R 2b , at each occurrence, is S substituted with 0-1 R 2c , O substituted with 0-1 R 2c , halogen, methanesulfonyl, NH 2 substituted with 0-2 R 2c , —CN, NO 2 , C 1-6 alkyl substituted with 0-2 R 2c , C 2-6 alkenyl substituted with 0-2 R 2c , aryl substituted with 0-2 R 2c , heteroaryl substituted with 0-2 R 2c , C 3-10 cycloalkyl substituted with 0-2 R 2c , or a heterocycle substituted with 0-2 R 2c ;

R 2c , at each occurrence, is S substituted with 0-1 R 2d , O substituted with 0-1 R 2d , halogen, NH 2 substituted with 0-2 R 2d , —CN, NO 2 , C 1-6 alkyl substituted with 0-2 R 2d , C 2-6 alkenyl substituted with 0-2 R 2d , aryl substituted with 0-2 R 2d , heteroaryl substituted with 0-2 R 2d , C 3-10 cycloalkyl substituted with 0-2 R 2d , or a heterocycle substituted with 0-2 R 2d ;

R 2d , at each occurrence, is OH, SH, S, O, halogen, NH 2 , —CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, aryl, CF 3 , or OCF 3 ;

R 3 is halogen or C 1-6 alkyl substituted with 0-2 R 3a ;

R 3a , at each occurrence, is OH, O, S, halogen, C(O)NH 2 , C(O)NH—C 1-4 alkyl, or C(O)N(C 1-4 alkyl) 2 ;

alternatively, R 3 and R 5e combine to form a 5, 6, or 7 membered ring consisting of carbon atoms and 0-2 heteroatoms selected from the group consisting of O, N, and S(O) 0-2 and there are 0-2 ring double bonds in the bridging portion formed by R 3 and R 5e ;

R 4a , at each occurrence, is H, halogen, or C 1-6 alkyl substituted with 0-2 R 4d ;

R 4d , at each occurrence, is OH, O, halogen, NH 2 , NH—C 1-4 alkyl, or N(C 1-4 alkyl) 2 ;

R 4b , at each occurrence, is H, halogen, or C 1-6 alkyl substituted with 0-2 R 4e ;

R 4e , at each occurrence, is OH, O, halogen, NH 2 , NH—C 1-4 alkyl, or N(C 1-4 alkyl) 2 ;

R 4c , at each occurrence, is H, halogen, or C 1-6 alkyl substituted with 0-2 R 4f ;

R 4f , at each occurrence, is OH, O, halogen, NH 2 , NH—C 1-4 alkyl, or N(C 1-4 alkyl) 2 ;

R 5a , at each occurrence, is H, halogen, CH 3 , or CH 2 CH 3 ;

R 5b , at each occurrence, is H, halogen, CH 3 , or CH 2 CH 3 ;

R 5c , at each occurrence, is H, halogen, CH 3 , or CH 2 CH 3 ;

R 5d , at each occurrence, is H, halogen, CH 3 , or CH 2 CH 3 ; and,

R 5e , at each occurrence, is H, halogen, CH 3 , or CH 2 CH 3 .

2. A compound according to claim 1 , wherein the compound is a compound of formula Ia:

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 , wherein the compound is a compound of formula II:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H, C 1-8 alkyl, heteroaryl, or C 3-10 cycloalkyl, wherein each R 1 group is substituted with 0-4 R 1a ;

R 1a , at each occurrence, is C 1-6 alkyl substituted with 0-3 R 1b ; C 2-6 alkynyl substituted with 0-2 R 1b ; aryl substituted with 0-2 R 1b , heteroaryl substituted with 0-2 R 1b , C 3-10 cycloalkyl substituted with 0-2 R 1b , or a heterocycle substituted with 0-2 R 1b ;

R 1b , at each occurrence, is OH substituted with 0-1 R 1c , SH substituted with 0-1 R 1c , Cl, F, NH 2 substituted with 0-2 R 1c , —CN, NO 2 , methanesulfonyl, C 1-4 alkyl substituted with 0-3 R 1c , C 2-4 alkenyl substituted with 0-2 R 1c , aryl substituted with 0-2 R 1c , heteroaryl substituted with 0-2 R 1c , C 3-6 cycloalkyl substituted with 0-2 R 1c , or a heterocycle substituted with 0-2 R 1c ;

R 1c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 1d , heteroaryl substituted with 0-2 R 1d , C 3-6 cycloalkyl substituted with 0-2 R 1d , or a heterocycle substituted with 0-2 R 1d ;

R 1d , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, or C 2-4 alkenyl;

R 2a is C 1-6 alkyl substituted with 0-2 R 2b , aryl substituted with 0-2 R 2b , or heteroaryl substituted with 0-2 R 2b ;

R 2b , at each occurrence, is OH substituted with 0-1 R 2c , SH substituted with 0-1 R 2c , Cl, F, NH 2 substituted with 0-2 R 2c , —CN, NO 2 , methanesulfonyl, C 1-4 alkyl substituted with 0-2 R 2c , C 2-4 alkenyl substituted with 0-2 R 2c , aryl substituted with 0-2 R 2c , heteroaryl substituted with 0-2 R 2c , C 3-6 cycloalkyl substituted with 0-2 R 2c , or a heterocycle substituted with 0-2 R 2c ;

R 2c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 2d , or heteroaryl substituted with 0-2 R 2d ;

R 2d , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, or C 2-4 alkenyl;

R 3 is Cl, F, CH 3 , or CH 2 CH 3 ;

alternatively, R 3 and R 5e combine to form a 5, 6, or 7 membered ring consisting of carbon atoms and 0-2 heteroatoms selected from the group consisting of O, N, and S(O) 0-2 and there are 0-2 ring double bonds in the bridging portion formed by R 3 and R 5e ;

R 4a , at each occurrence, is H, Cl, F, or CH 3 ;

R 4b , at each occurrence, is H, Cl, F, or CH 3 ;

R 4c , at each occurrence, is H, Cl, F, or CH 3 ;

R 5a , at each occurrence, is H, Cl, F, or CH 3 ;

R 5b , at each occurrence, is H, Cl, F, or CH 3 ;

R 5c , at each occurrence, is H, Cl, F, or CH 3 ;

R 5d , at each occurrence, is H, Cl, F, or CH 3 ; and,

R 5e , at each occurrence, is H, Cl, F, or CH 3 .

4. A compound according to claim 3 , wherein the compound is a compound of formula IIa:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H, C 1-6 alkyl, aryl, heteroaryl, or C 3-10 cycloalkyl, wherein each R 1 group is substituted with 0-1 R 1a ;

R 1a , at each occurrence, is C 1-6 alkyl substituted with 0-3 R 1b ; C 2-6 alkynyl substituted with 0-2 R 1b ; aryl substituted with 0-2 R 1b , heteroaryl substituted with 0-2 R 1b , C 5-6 cycloalkyl substituted with 0-2 R 1b , or a heterocycle substituted with 0-2 R 1b and;

R 1b , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , methanesulfonyl, C 1-4 alkyl substituted with 0-3 R 1c , C 2-4 alkenyl substituted with 0-2 R 1c , aryl substituted with 0-2 R 1c , heteroaryl substituted with 0-2 R 1c , C 5-6 cycloalkyl substituted with 0-2 R 1c , or a heterocycle substituted with 0-2 R 1c ;

R 1c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 1d , heteroaryl substituted with 0-2 R 1d , C 5-6 cycloalkyl substituted with 0-2 R 1d , or a heterocycle substituted with 0-2 R 1d ;

R 1d , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, or C 2-4 alkenyl;

R 2a is C 1-6 alkyl substituted with 0-2 R 2b , aryl substituted with 0-2 R 2b , or heteroaryl substituted with 0-2 R 2b ;

R 2b , at each occurrence, is OH substituted with 0-1 R 2c , SH, Cl, F, NH 2 , —CN, NO 2 , methanesulfonyl, C 1-4 alkyl, C 2-4 alkenyl, aryl, heteroaryl, C 5-6 cycloalkyl, or a heterocycle;

R 2c , at each occurrence, is C 1-4 alkyl;

R 3 is Cl, F, CH 3 , or CH 2 CH 3 ; and,

alternatively, R 3 and R 5e combine to form a 5, 6, or 7 membered ring consisting of carbon atoms and 0-2 heteroatoms selected from the group consisting of O, N, and S(O) 0-2 and there are 0-2 ring double bonds in the bridging portion formed by R 3 and R 5e .

5. A compound according to claim 4 wherein:

R 1 is H, C 1-6 alkyl, aryl, 5-6 membered heteroaryl consisting of carbon atoms and 1-2 heteroatoms selected from the group consisting of O and N; or C 3-10 cycloalkyl, wherein each R 1 group is substituted with 0-1 R 1a ;

R 1a , at each occurrence, is C 1-4 alkyl substituted with 0-3 R 1b ; C 2-6 alkynyl substituted with 0-1 R 1b , aryl substituted with 0-1 R 1b , heteroaryl substituted with 0-1 R 1b , C 5-6 cycloalkyl substituted with 0-1 R 1b , or a heterocycle substituted with 0-1 R 1b ;

R 1b , at each occurrence, is Cl, F, methanesulfonyl, or C 1-4 alkyl substituted with 0-3 R 1c , and;

R 1c , at each occurrence, is Cl, F or a heterocycle;

R 2a is C 1-6 alkyl substituted with 0-2 R 2b , aryl substituted with 0-2 R 2b , or heteroaryl substituted with 0-2 R 2b ;

R 2b , at each occurrence, is OH optionally substituted with C 1-4 alkyl, Cl, F, methanesulfonyl, aryl, heteroaryl, C 5-6 cycloalkyl, or a heterocycle;

R 3 is Cl, F, CH 3 , or CH 2 CH 3 .

6. A compound according to claim 5 wherein R 1 is C 1-4 alkyl substituted with 0-1 R 1a .

7. A compound according to claim 3 , wherein the compound is a compound of formula IIb

or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 7 , wherein R 2a is C 1-4 alkyl substituted with a heterocycle.

9. A compound according to claim 7 , wherein R 3 is Cl or CH 3 .

10. A compound according to claim 7 , wherein X is S or SCH 2 .

11. A compound according to claim 7 , wherein X is S.

12. A compound according to claim 7 , wherein X 1 is O.

13. A compound according to claim 1 , wherein the compound is a compound selected from the group consisting of:

{2-Chloro-4-[3-(4-chloro-phenylethynyl)-5-(3-piperidin-1-yl-propoxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-propoxy)-5-phenylethynyl-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Chloro-4-[3-(4-chloro-phenylethynyl)-5-(3-morpholin-4-yl-propoxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Chloro-4-[3-(4-chloro-phenylethynyl)-5-(4-morpholin-4-ylmethyl-benzyloxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Chloro-4-[3-(4-chloro-phenylethynyl)-5-(1-methyl-piperidin-4-ylmethoxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-propoxy)-5-(3-phenyl-prop-1-ynyl)-phenylsulfanyl]-phenoxy}-acetic acid;

{4-[3-(4-Fluoro-benzyloxy)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Cyclohexylmethoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(4-Chloro-benzyloxy)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{2-Chloro-4-[3-(4-chloro-phenylethynyl)-5-hydroxy-phenylsulfanyl]-phenoxy}-acetic acid;

{4-[3-But-2-ynyloxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{2-Methyl-4-[3-(2-morpholin-4-yl-ethoxy)-5-phenylethynyl-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Chloro-4-[3-(3-methoxy-prop-1-ynyl)-5-(3-morpholin-4-yl-propoxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Chloro-4-[3-(3-morpholin-4-yl-propoxy)-5-pent-1-ynyl-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-propoxy)-5-(3-phenyl-prop-1-ynyl)-benzylsulfanyl]-phenoxy}-acetic acid;

{4-[3-(4-Fluoro-benzyloxy)-5-(3-morpholin-4-yl-prop-1-ynyl)-benzylsulfanyl]-2-methylphenoxy}-acetic acid; and,

{2-Methyl-4-[3-(3-morpholin-4-yl-ethoxy)-5-(3-phenyl-prop-1-ynyl)-benzylsulfanyl]-phenoxy}-acetic acid;

or a pharmaceutically acceptable salt thereof.

14. A compound according to claim 1 , wherein the compound is a compound selected from the group consisting of:

{4-[3-Cyclohexylmethoxy-5-(4-methanesulfonyl-phenylethynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Cyclopentylmethoxy-5-(4-methanesulfonyl-phenylethynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Isobutoxy-5-(4-methanesulfonyl-phenylethynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(4-methanesulfonyl-phenylethynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-[2-(4-Chloro-phenyl)-ethoxy]-5-(4-hydroxymethyl-phenylethynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(2-Ethyl-butoxy)-5-phenylethynyl-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

[4-(3-Cyclopentyloxy-5-phenylethynyl-phenylsulfanyl)-2-methyl-phenoxy]-acetic acid;

{4-[3-(4-Fluoro-phenylethynyl)-5-(4-methanesulfonyl-benzyloxy)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

[4-(3-Cyclopentylmethoxy-5-phenylethynyl-phenylsulfanyl)-2-methyl-phenoxy]-acetic acid;

{4-[3-(2-Cyclohexyl-ethoxy)-5-phenylethynyl-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(2-Ethyl-butoxy)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-Cyclopentyloxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(2-Cyclohexyl-ethoxy)-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Cyclopentylmethoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid;

{4-[3-Cyclopentylmethoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic;

{4-[3-Isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-benzylsulfanyl]-2-methyl-phenoxy}-acetic acid;

[4-(3-Isobutoxy-5-phenylethynyl-benzylsulfanyl)-2-methyl-phenoxy]-acetic acid;

{4-[3-Isobutoxy-5-(4-methanesulfonyl-phenylethynyl)-benzylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(4-Methanesulfonyl-phenylethynyl)-5-(5-trifluoromethyl-pyridin-2-yloxy)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{4-[3-(4-Methanesulfonyl-phenylethynyl)-5-(3-trifluoromethyl-pyridin-2-yloxy)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-prop-1-ynyl)-5-(3-trifluoromethyl-pyridin-2-yloxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-prop-1-ynyl)-5-(5-trifluoromethyl-pyridin-2-yloxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{2-Methyl-4-[3-(3-morpholin-4-yl-prop-1-ynyl)-5-(3-trifluoromethyl-phenoxy)-phenylsulfanyl]-phenoxy}-acetic acid;

{4-[3-(4-Methanesulfonyl-phenylethynyl)-5-(3-trifluoromethyl-phenoxy)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid; and

{2-Methyl-4-[3-phenylethynyl-5-(5-trifluoromethyl-pyridin-2-yloxy)-phenylsulfanyl]-phenoxy}-acetic acid,

or a pharmaceutically acceptable salt thereof.

15. A compound according to claim 1 , wherein the compound is a compound of formula III:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is C 1-4 alkyl substituted with 1-2 R 1a ;

R 1a , at each occurrence, is aryl substituted with 0-2 R 1b , heteroaryl substituted with 0-2 R 1b , C 3-10 cycloalkyl substituted with 0-2 R 1b , or a heterocycle substituted with 0-2 R 1b ;

R 1b , at each occurrence, is OH substituted with 0-1 R 1c , SH substituted with 0-1 R 1c , Cl, F, NH 2 substituted with 0-2 R 1c , —CN, NO 2 , C 1-4 alkyl substituted with 0-2 R 1c , C 2-4 alkenyl substituted with 0-2 R 1c , aryl substituted with 0-2 R 1c , heteroaryl substituted with 0-2 R 1c , C 3-6 cycloalkyl substituted with 0-2 R 1c , or a heterocycle substituted with 0-2 R 1c ;

R 1c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 1d , heteroaryl substituted with 0-2 R 1d , C 3-6 cycloalkyl substituted with 0-2 R 1d , or a heterocycle substituted with 0-2 R 1d ;

R 1d , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, or C 2-4 alkenyl;

R 2a is aryl substituted with 0-2 R 2b or heteroaryl substituted with 0-2 R 2b ;

R 2b , at each occurrence, is OH substituted with 0-1 R 2c , SH substituted with 0-1 R 2c , Cl, F, NH 2 substituted with 0-2 R 2c , —CN, NO 2 , C 1-4 alkyl substituted with 0-2 R 2c , C 2-4 alkenyl substituted with 0-2 R 2c , aryl substituted with 0-2 R 2c , heteroaryl substituted with 0-2 R 2c , C 3-6 cycloalkyl substituted with 0-2 R 2c , or a heterocycle substituted with 0-2 R 2c ;

R 2c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 2d , or heteroaryl substituted with 0-2 R 2d ;

R 2d , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, or C 2-4 alkenyl;

R 3 is from Cl, F, CH 3 , or CH 2 CH 3 ;

alternatively, R 3 and R 5e combine to form a 5, 6, or 7 membered ring consisting of carbon atoms and 0-2 heteroatoms selected from the group consisting of O, N, and S(O) 0-2 and there are 0-2 ring double bonds in the bridging portion formed by R 3 and R 5e ;

R 4a , at each occurrence, is H, Cl, F, or CH 3 ;

R 4b , at each occurrence, is H, Cl, F, or CH 3 ;

R 4c , at each occurrence, is H, Cl, F, or CH 3 ;

R 5a , at each occurrence, is H, Cl, F, or CH 3 ;

R 5b , at each occurrence, is H, Cl, F, or CH 3 ;

R 5c , at each occurrence, is H, Cl, F, or CH 3 ;

R 5d , at each occurrence, is H, Cl, F, or CH 3 ; and,

R 5e , at each occurrence, is H, Cl, F, or CH 3 .

16. A compound according to claim 15 , wherein the compound is a compound of formula IIIa

or a pharmaceutically acceptable salt thereof, wherein:

R 1a , at each occurrence, is aryl substituted with 0-2 R 1b , heteroaryl substituted with 0-2 R 1b , C 5-6 cycloalkyl substituted with 0-2 R 1b , or a heterocycle substituted with 0-2 R 1b ;

R 1b , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl substituted with 0-2 R 1c , C 2-4 alkenyl substituted with 0-2 R 1c , aryl substituted with 0-2 R 1c , heteroaryl substituted with 0-2 R 1c , C 5-6 cycloalkyl substituted with 0-2 R 1c , or a heterocycle substituted with 0-2 R 1c ;

R 1c , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl substituted with 0-2 R 1d , heteroaryl substituted with 0-2 R 1d , C 3-6 cycloalkyl substituted with 0-2 R 1d , or a heterocycle substituted with 0-2 R 1d ;

R 2a is aryl substituted with 0-2 R 2b or heteroaryl substituted with 0-2 R 2b and; and,

R 2b , at each occurrence, is OH, SH, Cl, F, NH 2 , —CN, NO 2 , C 1-4 alkyl, C 2-4 alkenyl, aryl, heteroaryl, C 5-6 cycloalkyl, or a heterocycle.

17. A pharmaceutical composition comprising: a pharmaceutically acceptable carrier and a compound according to claim 1 .

18. {4-[3-Isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methylphenoxy}-acetic acid or a pharmaceutically acceptable salt thereof.

19. A compound according to claim 18 , where the compound is {4-[3-isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-phenylsulfanyl]-2-methyl-phenoxy}-acetic acid.

20. {4-[3-Isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-benzylsulfanyl]-2-methylphenoxy}-acetic acid or a pharmaceutically acceptable salt thereof.

21. A compound according to claim 18 , where the compound is {4-[3-isobutoxy-5-(3-morpholin-4-yl-prop-1-ynyl)-benzylsulfanyl]-2-methyl-phenoxy}-acetic acid.

22. A pharmaceutical composition comprising a compound of claim 18 and a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising a compound of claim 19 and a pharmaceutically acceptable carrier.

24. A pharmaceutical composition comprising a compound of claim 20 and a pharmaceutically acceptable carrier.

25. A pharmaceutical composition comprising a compound of claim 21 and a pharmaceutically acceptable carrier.

Assignments (12)