Substituted tetrahydroisoquinoline compounds useful as GPR120 agonists

1. A compound according to the formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is

(1) bond,

(2) (C 1-2 )alkyl, or

(3) halo(C 1-2 )alkyl;

ring A is phenyl, pyridine, pyrimidine, pyrazole, pyrazine, isothiazole, or benzisoxazole;

R 1 is a

R 2 is

(1) hydroxy,

(2) COOH,

(3) tetrazole,

(5) hydroxyisoxazole,

(6) triazole,

(7) C(O)NH 2 ,

(8) C(O)NHC 1-6 alkyl,

(9) C(O)NHC 3-6 cycloalkyl,

(10) C(O)NHC 2-5 cycloheteroalkyl,

(11) C(O)NH-aryl,

(12) C(O)NH-heteroaryl,

(13) SO 2 C 1-6 alkyl,

(14) SO 2 C 3-6 cycloalkyl,

(15) SO 2 C 2-5 cycloheteroalkyl,

(16) SO 2 -aryl, or

(17) SO 2 -heteroaryl;

R 3 is

(1) hydrogen,

(2) halogen,

(3) cyano, or

(4) (C 1-3 )alkyl;

R 4 is

(1) hydrogen,

(2) (C 1-3 )alkyl,

(3) halo(C 1-3 )alkyl, or

(4) halogen;

R 5 is

(1) cyano,

(2) (C 1-3 )alkyl,

(3) halo(C 1-3 )alkyl,

(4) (C 1-3 )alkoxy,

(5) halo(C 1-3 )alkoxy, or

(6) halogen;

R 6 is

(1) (C 1-3 )alkoxy,

(2) halo(C 1-3 )alkoxy,

(3) halo(C 1-3 )alkyl,

(4) (C 3-6 )cycloalkyl,

(5) (C 3-6 )cycloalkyl-O-,

(6) (C 3-6 )cycloalkyl-S-,

(7) (C 3-6 )cycloalkyl-(C 1-2 )alkyl-,

(8) (C 3-6 )cycloalkyl-halo(C 1-2 )alkyl-,

(9) phenyl,

(10) 5- to 6-membered heteroaryl-O- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S, or

(11) 5- to 6-membered heteroaryl- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S,

wherein alkyl, cycloalkyl, phenyl and heteroaryl are unsubstituted or substituted with 1-3 substituents selected from (C 1-3 )alkyl, halo(C 1-3 )alkyl, (C 1 - 3 )alkoxy, halo(C 1-3 )alkoxy, and halogen;

n is 0, 1, 2 or 3;

m is 1;

p is 0, 1, 2 or 3; and

q is 0, 1, or 2.

2. The compound of claim 1 wherein X is

(1) bond, or

(2) (C 1 - 2 )alkyl;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein X is a bond; or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 wherein

R 2 is

(1) hydroxy,

(2) COOH, or

(3) tetrazole;

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 wherein R 2 is COOH; or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 wherein R 3 is

(1) hydrogen,

(2) halogen, or

(3) (C 1-3 )alkyl;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 wherein R 3 is

(1) hydrogen, or

(2) halogen;

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 wherein R 4 is

(1) hydrogen, or

(C 1-3 )alkyl;

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 wherein R 4 is hydrogen; or

a pharmaceutically acceptable salt thereof.

10. The compound of claim 1 wherein R 5 is

(1) cyano,

(2) (C1-3)alkyl,

(3) halo(C1-3)alkyl,

(4) (C1-3)alkoxy, or

(5) halogen;

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 wherein R 5 is

(1) cyano, or

(2) halogen;

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 wherein R 6 is

(1) halo(C 1-3 )alkoxy,

(2) halo(C 1-3 )alkyl,

(3) (C 3-6 )cycloalkyl,

(4) (C 3-6 )cycloalkyl-O-,

(5) (C 3-6 )cycloalkyl-S-,

(6) (C 3-6 )cycloalkyl-(C 1-2 )alkyl-,

(7) phenyl,

(8) 5- to 6-membered heteroaryl-O- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S, or

(9) 5- to 6-membered heteroaryl- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S,

wherein alkyl, cycloalkyl, phenyl and heteroaryl are unsubstituted or substituted with 1-3 substituents selected from (C 1-3 )alkyl, halo(C 1-3 )alkyl, (C 1-3 )alkoxy, halo(C 1-3 )alkoxy, and halogen; or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 wherein R 6 is (C 3-6 )cycloalkyl-O-, wherein cycloalkyl is unsubstituted or substituted with 1-3 substituents selected from (C 1 - 3 )alkyl, halo(C 1-3 )alkyl, (C 1-3 )alkoxy, halo(C 1-3 )alkoxy, and halogen; or a pharmaceutically acceptable salt thereof.

14. A compound according to the formula I:

wherein:

X is

(1) a bond, or

(2) (C 1-2 )alkyl;

ring A is phenyl, pyridine, pyrimidine, pyrazole, pyrazine, isothiaozole, or benzisoxazole;

R 1 is

R 2 is

(1) hydroxy,

(2) COOH, or

(3) tetrazole;

R 3 is

(1) hydrogen,

(2) halogen, or

(3) (C 1-3 )alkyl;

R 4 is

(1) hydrogen, or

(2) (C 1-3 )alkyl;

R 5 is

(1) cyano,

(2) (C 1-3 )alkyl,

(3) halo(C 1-3 )alkyl,

(4) (C 1-3 )alkoxy, or

(5) halogen;

R 6 is

(1) halo(C 1-3 )alkoxy,

(2) halo(C 1-3 )alkyl,

(3) (C 3-6 )cycloalkyl,

(4) (C 3-6 )cycloalkyl-O-,

(5) (C 3-6 )cycloalkyl-S-,

(6) (C 3-6 )cycloalkyl-(C 1-2 )alkyl-,

(7) phenyl,

(8) 5- to 6-membered heteroaryl-O- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S, or

(9) 5- to 6-membered heteroaryl- wherein the heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, O and S,

wherein alkyl, cycloalkyl, phenyl and heteroaryl are unsubstituted or substituted with 1-3 substituents selected from (C 1-3 )alkyl, halo(C 1-3 )alkyl, (C 1-3 )alkoxy, halo(C 1-3 )alkoxy, and halogen;

n is 0, 1, 2 or 3;

m is 1;

p is 0, 1, 2 or 3; and

q is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

15. A compound according to the formula I:

wherein:

X is a bond;

ring A is aryl;

R 1 is (C 1-6 )alkyl;

R 2 is COOH;

R 3 is

(1) hydrogen, or

(2) halogen;

R 4 is hydrogen;

R 5 is

(1) cyano, or

(2) halogen;

R 6 is (C 3-6 )cycloalkyl-O-, wherein cycloalkyl is unsubstituted or substituted with 1-3 substituents selected from (C 1-3 )alkyl, halo(C 1-3 )alkyl, (C 1-3 )alkoxy, halo(C 1-3 )alkoxy, and halogen;

n is 0, 1, 2 or 3;

m is 1;

p is 0, 1, 2 or 3; and

q is 0, 1, or 2, or a pharmaceutically acceptable salt thereof.

16. A compound selected from the group consisting of:

1) 3-(2-(2-chloro-5-cyclobutoxy-4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-propanoic acid;

2) 3-(2-(3-(difluoromethyl)-2-fluoro-5-(pyridin-2-yloxy)phenyl)-1,2,3,4-tetra-hydro-isoquinolin-6-yl)propanoic acid;

3) 3-(2-(2,3-difluoro-5-(3-methoxycyclobutoxy)phenyl)-1,2,3,4-tetrahydroiso-quinolin-6-yl)-propanoic acid;

4) 3-(2-(2-fluoro-4-methoxy-5-((5-methylthiazol-2-yl)oxy)phenyl)-1,2,3,4-tetra-hydroisoquinolin-6-yl)propanoic acid;

5) 3-(2-(6-cyclobutoxy-3-fluoropyridin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6- yl)-propanoic acid;

6) 3-(2-(5-cyclobutoxy-2-fluorophenyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-propanoic acid;

7) 3-(2-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroisoquinolin-6-yl) butanoic acid;

8) 3-(2-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydro-isoquinolin-6-yl)-butanoic acid;

9) 3-(2-{3-chloro-2-fluoro-5-[(5-methyl- 1,3-thiazol-2-yl)oxy]phenyl}-1,2,3,4-tetrahydro- isoquinolin-6-yl)propanoic acid;

10) 3- {2- [5-(cyclobutyloxy)-3-(difluoromethyl)-2-fluorophenyl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

11) 3- {2- [5-(cyclobutyloxy)-2,3-difluorophenyl]-1,2,3,4-tetrahydroisoquinolin- 6-yl}-propanoic acid;

12) 3- {2- [3-cyano-5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

13) 3- {2-[2-fluoro-3-methoxy-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

14) 3-(2- {3-(difluoromethyl)-2-fluoro-5-[(5-methyl- 1,3-thiazol-2-yl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

15) 3- {2- [3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

16) 3-(2- {3-(difluoromethyl)-2-fluoro-5-[(5-methylpyridin-2-yl)oxy]phenyl-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

17) 3-(2-{2-fluoro-3-methoxy-5-[(5-methyl-1,3-thiazol-2-yl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)propanoic acid;

18) 3-{2-[5-(cyclobutyloxy)-2-fluoro-3-methoxyphenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

19) 3-{2- [5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

20) 3-(2-{2,3-difluoro-5-[(trans-3-methoxycyclobutyl)oxy]phenyl}-1,2,3,4-tetrahydro-isoquinolin-6-yl)propanoic acid;

21) 3-(2-{2-fluoro-4-methoxy-5-[(5-methyl-1,3-thiazol-2-yl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

22) 3-{2- [4-chloro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

23) 3-{2- [5-(cyclobutylmethyl)-2-fluorophenyl]-5-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

24) 3-{2-[2-chloro-5-(cyclobutyloxy)-4-methoxyphenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

25) 3-{2-[6-(cyclobutyloxy)-3-fluoropyridin-2-yl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

26) 3-{2- [2-(cyclobutylsulfanyl)-5-fluoropyridin-4-yl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

27) 3-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

28) 3-(2-{2-fluoro-4-methoxy-5-[(5-methylpyridin-2-yl)oxy]phenyl }-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

29) 3-{2-[6-fluoro-3-(trifluoromethyl)-1,2-benzisoxazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

30) 3-{7-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

31) 3-{2- [5-(cyclobutyloxy)-2-fluoro-4-methoxyphenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

32) 3-{2-[5-(cyclobutyloxy)-2,3-difluorophenyl]-1-methyl-1,2,3,4-tetrahydro-isoquinolin-6- yl}propanoic acid;

33) 3-{2-[2-fluoro-5-(pyrazin-2-yloxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

34) 3-(2-{3-cyano-2-fluoro-5- [(trans-3-methoxycyclobutyl)oxy]phenyl}1-1,2,3,4-tetrahydro- isoquinolin-6-yl)propanoic acid;

35) 3-(2-{3-(difluoromethyl)-2-fluoro-5-[(5-fluoropyridin-2-yl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

36) 3-{2-[5-(cyclobutyloxy)-2-fluorophenyl]-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

37) 3-{2-[2-chloro-5-(cyclobutyloxy)-3-fluorophenyl]-1-methyl-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

38) 3-{2-[6-(cyclobutylsulfanyl)pyridin-2-yl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

39) 3- {2-[5-(cyclobutyloxy)-2-fluorophenyl]-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

40) 3- {2-[3,5-dichloro-4-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

41) 3-{2-[6-(cyclobutyloxy)pyrazin-2-yl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

42) 3-{2-[2-cyano-5-(cyclobutyloxy)-4-methoxy phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}-propanoic acid;

43) 3- {2-[4-cyano-1-(4-methoxy phenyl)-3-methyl-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydro- isoquinolin-6-yl}propanoic acid;

44) 3-{2-[2-cyano-3-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

45) 3-{2-[2-chloro-5-(cyclobutyloxy)-3-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

46) 3-{2-[2-cyano-5-(cyclobutyloxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

47) 3-{2-[4-fluoro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

48) 3-(2-{12-cyano-5-[(trans-3-methoxycyclobutyl)oxy]phenyl}-1,2,3,4-tetra-hydroisoquinolin-6-yl)-propanoic acid;

49) 3- {2- [5-(cyclobutyloxy)-2,3-difluorophenyl]-1-methyl-1,2,3,4-tetrahydro-isoquinolin-6- yl}-propanoic acid;

50) 3-(2-{[3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

51) 3-{8-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

52) 3-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-2-methyl-propanoic acid;

53) 3-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-butanoic acid;

54) 3- {2- [3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

55) 3- {2-[2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

56) 3-(2-(5-(cyclobutyldifluoromethyl)-2-fluorophenyl)-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl)propanoic acid;

57) 3-(2-(3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl)-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl)-2-methylpropanoic acid;

58) 3-(5-fluoro-2-(2-fluoro-5-(trifluoromethoxy)phenyl)-7-methyl-1,2,3,4-tetra-hydroisoquinolin-6-yl)propanoic acid;

59) 3-(2-(3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl)-5-fluoro-1,2,3,4-tetra-hydro-isoquinolin-6-yl)propanoic acid;

60) 3-(2-(5-(cyclobutylmethyl)-2-fluorophenyl)-5-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl)-propanoic acid;

61) 3-(2-(5-cyclobutoxy-2-fluorophenyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)-propanoic acid;

62) 3-(2-{3-chloro-2-fluoro-5-[(5-methyl-1,3-thiazol-2-yl)oxy]phenyl}-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)propanoic acid;

63) 3- {2- [6-(cyclobutyloxy)-3-fluoropyridin-2-yl]-5-fluoro-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

64) 3- {2- [5-(cyclobutyloxy)-2,3-difluorophenyl]-5-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

65) 3-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

66) 3-(2- {2,3-difluoro-5- [(trans-3-methoxycyclobutyl)oxy]phenyl}-5-fluoro-1,2,3,4-tetra- hydroisoquinolin-6-yl)propanoic acid;

67) 3-(2-{5-[cyclobutyl(difluoro)methyl]-2-fluorophenyl}-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

68) 3-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}-2-methylpropanoic acid;

69) 3-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}-2-methylpropanoic acid;

70) 3-{5-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-7-methyl-1,2,3,4-tetra-hydro-isoquinolin-6-yl}propanoic acid;

71) 3-{2 [4-chloro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

72) 3-{5-chloro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydro-isoquinolin-6- yl}propanoic acid;

73) 3-{2 [3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl]-5-fluoro-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

74) 3-{2 [5-(cyclobutylmethyl)-2-fluorophenyl]-fluoro-1,2,3,4-tetrahydro-isoquinolin-6-yl}propanoic acid;

75)3 [2-(5-{[3-(difluoromethyl)cyclobutyl]oxy}-2,3-difluorophenyl)-5-fluoro-1,2,3,4-tetra- hydroisoquinolin-6-yl]propanoic acid;

76) 3-{2-[2-cyano-5-(cyclobutyloxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

77) 3-{5-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}-2-methylpropanoic acid;

78) 3-{2-[2-cyano-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

79) 3-(2-(2-cyano-5-cyclobutoxy-3-fluorophenyl)-5-fluoro-1,2,3,4-tetrahydro-isoquinolin-6- yl)-2-methylpropanoic acid;

80) 3-{5-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

81) 3-{2- [5-(cyclobutyloxy)-2-fluorophenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

82) 3-{2- [2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

83) (1S,2S)-2-(2-(2,3-difluoro-5-((1R,3S)-3-methylcyclobutoxy)phenyl)-1,2,3,4-tetrahydro- isoquinolin-6-yl)cyclopropanecarboxylic acid;

84) 2-(2-(2-fluoro-5-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-cyclo-propanecarboxylic acid;

85) (1R,2R)-2-{2-[5-(cyclobutyloxy)-2,3-difluorophenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropane- carboxylic acid;

86) (1R,2R)-2-{2-[3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

87) (1R,2R)-2-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropanecarboxylic acid;

88) (1S,2 S)-2-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropanecarboxylic acid;

89) (1R,2R)-2-(2-{3-cyano-2-fluoro-5- [(trans-3-methoxycyclobutyl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

90) (1S,2 S)-2-{2-[2-fluoro-5-(trifluoromethoxy)benzyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropanecarboxylic acid;

91) (1S,2 S)-2-{2- [3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

92) 2-{2- [4-fluoro-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

93) (1S,2S)-2-{2- [3-chloro-2-fluoro-5-(trifluoromethyl)benzyl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

94) 2-{2-[4-fluoro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

95) 2-{2- [4-fluoro-1-(4-fluorophenyl)-3-methyl-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

96) 2-{2-[4-fluoro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

97) (1 S,2S)-2-(2-{2-cyano-3-methoxy-5- [(trans-3-methoxycyclobutyl)oxy]-phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

98) (1 S,2S)-2-(2-{2,3-difluoro-5- [(trans-3-methylcyclobutyl)oxy]phenyl}-1,2,3,4-tetra-hydroisoquinolin-6-yl) cyclopropanecarboxylic acid;

99) (1R,2R)-2-(2-{2,3-difluoro-5-[(trans-3-methoxycyclobutyl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

100) (1S,2S)-2-(2-{2,3-difluoro-5-[(trans-3-methoxycyclobutyl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

101) (1R,2R)-2-(2-{2,3-difluoro-5-[(trans-3-methylcyclobutyl)oxy]phenyl}-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

102) 2-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-cyclopropanecarboxylic acid;

103) (1R,2R)-2-(2-{2-cyano-3-fluoro-5-[(trans-3-methoxycyclobutyl)oxy]phenyl }-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

104) 2-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropanecarboxylic acid;

105) 2-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroiso-quinolin-6-yl}cyclopropanecarboxylic acid;

106) (1S,2S)-2-(2-(2,3-difluoro-5-((1r,3S)-3-methoxycyclobutoxy)phenyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

107) (1S,2S)-2-(2-(3-cyano-2-fluoro-5-(trifluoromethoxy)phenyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

108) (1S,2S)-2-(2-(2,3-difluoro-5-((1r,3S)-3-methylcyclobutoxy)phenyl)-4-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

109) (1R,2R)-2-{2- [3-cyano-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

110) (1R,2R)-2-(2-{2,3-difluoro-5-[(trans-3-methoxy cyclobutyl)oxy]phenyl }-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

111) (1R,2R)-2-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

112) (1R,2R)-2-(2-{2,3-difluoro-5-[(trans-3-methylcyclobutyl)oxy]phenyl}-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

113) (1R,2R)-2-{5-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}cyclopropanecarboxylic acid;

114) (1R,2R)-2-{2- [3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

115) (1S,2S)-2-(2-{2,3-difluoro-5-[(trans-3-methoxy cyclobutyl)oxy]phenyl}-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

116) (1S,2S)-2-{2-[3-cyano-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

117) (1S,2S)-2-{2-[2-cyano-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

118) (1S,2S)-2-{5-fluoro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}cyclopropanecarboxylic acid;

119) (1S,2S)-2-{2-[2-cyano-3-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

120) (1S,2S)-2-{2-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

121) (1R,2R)-2-{2-[2-chloro-3-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

122) (1S,2S)-2-(2-{2,3-difluoro-5-[(trans-3-methylcyclobutyl)oxy]phenyl}-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)cyclopropanecarboxylic acid;

123) (1R,2R)-2-{2- [3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-5-fluoro-1,2,3,4-tetra hydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

124) (1S,2S)-2-{2-[2-chloro-3-fluoro-5-(trifluoromethoxy)phenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

125) (1S,2S)-2-{2-[3-chloro-5-(cyclobutyloxy)-2-fluorophenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

126) (1S,2S)-2-{2-[2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}cyclopropanecarboxylic acid;

127) 5-(2-(4-cyano-3-methyl-1-(p-tolyl)-1H-pyrazol-5-yl)-1,2,3,4-tetrahydro-isoquinolin-6-yl)pentanoic acid;

128) 5-(2-(4-cyano-3-methyl-1-(p-tolyl)-1H-pyrazol-5-yl)-1,2,3,4-tetrahydroiso-quinolin-6-yl)hexanoic acid;

129) 5-(6-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-methyl-1-(p-tolyl)-1H-pyrazole-4-carbonitrile;

130) 5-(6-(2-hydroxyethoxy)-3,4-dihydroisoquinolin-2(1H)-yl)-3-methyl-1-(p-tolyl)-1H-pyrazole-4-carbonitrile;

131) 3-(2-(5-cyclobutoxy-2,3-difluorophenyl)-7-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl)- propanoic acid;

132) 6-(2-(1H-tetrazol-5-yl)ethyl)-2-(2,3-difluoro-5-((1r,3r)-3-methoxylcyclo-butoxy)-phenyl)-1,2,3,4-tetrahydroisoquinoline;

133) 5-{2- [4-cyano-1-(4-methoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-1,2,3,4-tetrahydro- isoquinolin-6-yl}pentanoic acid;

134) 5-{2-[4-cyano-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}pentanoic acid;

135) 5-{2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}-pentanoic acid;

136) 5-[6-(2-hydroxyethoxy)-3,4-dihydroisoquinolin-2(1H)-yl]-3-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carbonitrile;

137) 5-{2-[4-chloro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}pentanoic acid;

138) 5-(6-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carbonitrile;

139) 5-[6-(4-hydroxybutoxy)-3,4-dihydroisoquinolin-2(1H)-yl]-3-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carbonitrile;

140) 5-{2-[4-cyano-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}hexanoic acid;

141) 5-(3,4-dihydroisoquinolin-2(1H)-yl)-1-(4-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbonitrile;

142) 5-{2-[4-cyano-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-1,2,3,4-tetrahydro-isoquinolin-6-yl}hexanoic acid;

143) 3-(2-1[4-fluoro-3-methyl-1-(4-methyl phenyl)-1H-pyrazol-5-yl]methyl}-1,2,3,4-tetrahydroisoquinolin-6-yl) propanoic acid;

144) 5-[6-(3-hydroxypropoxy)-3,4-dihydroisoquinolin-2(1H)-yl]-3-methyl-1-(4-methylphenyl)-1H-pyrazole-4-carbonitrile;

145) 3-2-[5-(cyclobutyloxy)-2,3-difluorophenyl]-7-fluoro-1,2,3,4-tetrahydroiso-quinolin-6-yl}propanoic acid;

146) 3-2-[4-chloro-3-methyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-5-fluoro-1,2,3,4-tetrahydro- isoquinolin-6-yl}propanoic acid;

147) 3-2-[3-chloro-2-cyano-5-(cyclobutyloxy)phenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

148) 3-{2-[5-cyano-4-(cyclobutyloxy)-6-methylpyrimidin-2-yl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

149) 3-{2-[5-cyano-2-(cyclobutyloxy)-6-methylpyrimidin-4-yl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

150) 3-{5-chloro-2-[2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

151) 342-(6-cyclopropylpyridin-2-yl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}-propanoic acid;

152) 3-{2-[2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-5-fluoro-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

153) 3-{2-[2,3-dichloro-5-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

154) 3-{2-[2-cyano-5-(cyclobutyloxy)-3-fluorophenyl]-5-methyl-1,2,3,4-tetra-hydroisoquinolin-6-yl}propanoic acid;

155) 3-{2-[6-(cyclobutyloxy)-3-fluoro-4-methoxypyridin-2-yl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

156) 3-{2-[3-cyano-6-(cyclobutyloxy)-2-methylpyridin-4-yl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid; and

157) 3-{2-[3-cyano-4-methyl-6-(1,3-thiazol-4-yl)pyridin-2-yl]-5-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl}propanoic acid;

or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier.