Oxo-tetrahydro-isoquinoline carboxylic acids as STING inhibitors

1. A compound of formula I or a pharmaceutically acceptable salt thereof:

wherein: A is a 5- to 7-membered unsaturated non-aromatic ring having 1 or 2 heteroatoms independently selected from oxygen, nitrogen and sulfur;

R 1 is selected from —OH amino, —NHOH, —N(C 1-6 alky) 2 , and —N(C 1-6 alkyl);

n is 0, 1, 2, or 3;

z is 0, 1, 2, or 3;

y is 0, 1, 2, or 3;

each R 3 is independently selected from C 1-10 alkyl, C 1-10 haloalkyl, C 3-7 cycloalkylC 0-6 alkyl, and C 3-7 heterocycloalkylC 0-6 alkyl,

R 2 is phenyl or pyridyl, wherein R 2 is substituted by 0, 1, 2, or 3 R 5 substituents and wherein two R 5 may join together with the ring atoms to which they are attached to form a 3- to 6-membered ring;

each R 4 is independently selected from halogen, —(C 1-6 alkyl)OH, hydroxy, C 1-10 haloalkyl, C 2-10 alkenyl, C 1-6 alkyl, and aryl(C 0-10 alkyl)oxy(C 0-10 alkyl);

each R 5 is independently selected from:

halogen,

C 1-10 alkyl(oxy) 0-1 C 0-10 alkyl,

C 1-10 heteroalkyl(oxy) 0-1 C 0-10 alkyl,

C 2-10 alkenyl(oxy) 0-1 C 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 C 0-10 alkyl,

C 3-12 cycloalkyl C 0-10 alkyl(oxy) 0-1 C 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 C 0-10 alkyl,

(C 3-12 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 C 0-10 alkyl,

amino,

C 1-10 alkylaminoC 0-10 alkyl,

(C 1-10 )heteroalkyl(oxy) 0-1 (carbonyl) 0-1 aminoC 0-10 alkyl,

C 3-12 cycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 aminoC 0-10 alkyl,

aryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 aminoC 0-10 alkyl,

heteroaryl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 aminoC 0-10 alkyl,

(C 3-12 )heterocycloalkyl C 0-10 alkyl(oxy) 0-1 (carbonyl) 0-1 aminoC 0-10 alkyl,

C 0-10 alkylamino (carbonyl) 0-1 C 0-10 alkyl,

(C 1-10 )heteroalkylamino (carbonyl) 0-1 C 0-10 alkyl,

C 3-12 cycloalkylamino (carbonyl) 0-1 C 0-10 alkyl,

aryl C 0-10 alkylamino (carbonyl)C 0-10 alkyl,

heteroaryl C 0-10 alkylamino(carbonyl) 0-1 C 0-10 alkyl,

(C 3-12 )heterocycloalkylamino(carbonyl) 0-1 C 0-10 alkyl,

C 1-10 alkylsulfonylC 0-10 alkyl,

C 1-10 heteroalkylsulfonylC 1-10 alkyl,

(C 3-12 )cycloalkylC 0-10 alkylsulfonylC 0-10 alkyl,

(C 3-12 )cycloheteroalkylC 0-10 alkylsulfonylC 0-10 alkyl,

heteroarylC 0-10 alkylsulfonylC 0-10 alkyl,

arylC 0-10 alkylsulfonylC 0-10 alkyl,

C 1-10 alkylsulfonylaminoC 0-10 alkyl,

(C 1-10 alkyl) 1-2 amino,

—SO 2 NH 2 ,

SO 2 NH(C 1-10 alkyl),

—SO 2 N(C 1-10 alkyl) 2 ,

—SO 2 CF 3 ,

—SO 2 CF 2 H,

—SH,

—S(C 1-10 alkyl),

—NH═CH 2 ,

hydroxy,

—(C 1-10 alkyl)OH,

—C 0-10 alkylalkoxy,

cyano,

—(C 1-6 alkyl)cyano, and

C 1-6 haloalkyl(oxy) 0-1 ; wherein each R 5 is substituted with 0, 1, 2 or 3 R 6 substituents each independently selected by halogen, cyano, oxo, C 1-10 alkylcarbonylC 0-10 alkyl, C 1-10 alkyl, C 1-10 alkylcarbonylaminoC 0-10 alkyl, and —(C 1-10 alkyl)OH.

2. The compound according to claim 1 , wherein R 1 is selected from —OH, amino, —NHOH, —N(C 1-3 alkyl) 2 , and —N(C 1-3 alkyl) or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 , wherein R 1 is selected from —OH, amino, —NHOH, dimethylamino, and methylamino or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein each R 3 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-7 cycloalkylC 0-6 alkyl, and C 3-7 heterocycloalkylC 0-6 alkyl or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein each R 3 is independently selected from methyl, isopropyl, and cyclopropyl or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein each R 4 is independently selected from halogen, hydroxy, C 2-10 alkenyl, and aryl(C 0-10 alkyl)oxy(C 0-10 alkyl) or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 , wherein each R 4 is independently selected from halogen, hydroxy, ethenyl, and phenylmethoxy or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 , wherein each R 5 is independently selected from: halogen, C 1-6 alkyl(oxy) 0-1 C 0-10 alkyl, C 2-10 alkenyl, aryl C 0-10 alkyl(oxy) 0-1 C 0-10 alkyl, C 3-12 cycloalkyl C 0-10 alkyl, heteroaryl C 0-10 alkyl, (C 3-12 )heterocycloalkyl C 0-10 alkyl, C 1-10 alkylaminoC 0-10 alkyl, aryl C 0-10 alkylamino (carbonyl)C 0-10 alkyl, C 1-10 alkylsulfonylC 0-10 alkyl, C 1-10 alkylsulfonylaminoC 0-10 alkyl, (C 1-10 alkyl) 1-2 amino, —SO 2 NH(C 1-10 alkyl), —SO2N(C 1-10 alkyl) 2 , —SH, —NH═CH 2 , —(C 1-10 alkyl)OH, —C 0-10 alkylalkoxy, cyano, —(C 1-6 alkyl)cyano, and C 1-6 haloalkyl(oxy) 0-1 ; wherein each R 5 is substituted with 0, 1, 2, or 3 R 6 substituents or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 8 , wherein each R 5 is independently selected from: F, Cl, tert-butyl, isopropyl, methyl, ethyl, morpholinyl, methylsufonyl, dimethysulfamoyl, 1-cyano-1-methylethyl, cyclopropyl, piperazinyl, pyrazolyl, methoxy, —SH, —N═CH 2 , methylamino, cyano, hydroxyethyl, 2,2,2-trifluoroethyloxy, phenylaminocarbonyl, cyclohexyl, propyl, ((methylsulfonyl)amino)methyl, morpholinylmethyl, phenylmethyloxy, Br, prop-2-enyl, hydroxymethyl, phenyl, and piperidinyl, wherein each R 5 is substituted with 0, 1, 2 or 3 R 6 substituents or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 9 , wherein each R 6 is independently selected from halogen, cyano, oxo, C 1-6 alkylcarbonyl, C 1-6 alkyl, C 1-6 alkylcarbonylamino, and (C 1-10 alkyl)OH or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 , wherein each R 6 is independently selected from halogen, methylcarbonyl, hydroxyethyl, oxo, cyano, hydroxymethyl, methylcarbonyl amino, and methyl or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 , wherein R 5 is selected from hydrogen, methyl, methylcarbonyl, ethyl, isopropyl, morpholinoethyl, 2-hydroxy-2-methylpropyl, 2-hydroxyethyl, 1-phenylethyl, benzyl, tetrahydro-2H-pyranylmethyl, 1-cyclopropylethyl, and tetrahydro-2H-pyranyl or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 11 , wherein R 6 is hydrogen or oxo or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 , wherein

is selected from:

or a pharmaceutically acceptable salt thereof.

15. The compound or a pharmaceutically acceptable salt, thereof, wherein the compound is selected from:

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(1-methylethyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(1-methylethyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2,3-dihydro-11H-inden-5-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2,3-dihydro-1H-inden-5-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(4-morpholin-4-ylphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(4-morpholin-4-ylphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(methylsulfonyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(methylsulfonyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(dimethylsulfamoyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(dimethylsulfamoyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)(-2-[4-(1-cyano-1-methylethyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S) (-2-[4-(1-cyano-1-methylethyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(2-chloropyridin-4-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(2-chloropyridin-4-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-cyclopropylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-cyclopropylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(4-acetylpiperazin-1-yl)phenyl]-3-(2,3-dihydro-,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R))-2-[4-(4-acetylpiperazin-1-yl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(4-acetylpiperazin-1-yl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(4-acetylpiperazin-1-yl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{4-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]phenyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{4-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]phenyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(difluoromethoxy)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(difluoromethoxy)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(1,3-benzothiazol-5-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(1,3-benzothiazol-5-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,3-diethyl-2-oxo-2,3-dihydro-1H-indol-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-[4-(1H-pyrazol-5-yl)phenyl]-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-[4-(1H-pyrazol-5-yl)phenyl]-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-chloro-3-fluorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-chloro-3-fluorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-chloro-3-cyclopropylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-chloro-3-cyclopropylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3-cyano-4-morpholin-4-ylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3-cyano-4-morpholin-4-ylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[3-chloro-4-(difluoromethoxy)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[3-chloro-4-(difluoromethoxy)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(2-hydroxy-1,1-dimethylethyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[4-(2-hydroxy-1,1-dimethylethyl)phenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3-chloro-4-morpholin-4-ylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3-chloro-4-morpholin-4-ylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-methylpyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-methylpyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-[4-(2,2,2-trifluoroethoxy)phenyl]-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-[4-(2,2,2-trifluoroethoxy)phenyl]-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-{4-[(4-chlorophenyl)carbamoyl]phenyl}-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-{4-[(4-chlorophenyl)carbamoyl]phenyl}-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-cyclohexylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-cyclohexylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4R)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-fluoropyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2-fluoropyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(2-chloro-6-methylpyridin-4-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(2-chloro-6-methylpyridin-4-yl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-chloro-3-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-chloro-3-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(4-{[(methylsulfonyl)amino]methyl}phenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(4-{[(methylsulfonyl)amino]methyl}phenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2,6-dimethylpyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-,4-benzodioxin-6-yl)-2-(2,6-dimethylpyridin-4-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[3-chloro-4-(morpholin-4-ylmethyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[3-chloro-4-(morpholin-4-ylmethyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,4-dimethylphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,4-dimethylphenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3,4-dichlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3,4-dichlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(benzyloxy)-3-chlorophenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(benzyloxy)-3-chlorophenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3-bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3-bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-cyclopropyl-3-fluorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-cyclopropyl-3-fluorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(3,4-dihydro-2H-1-,5-benzodioxepin-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(1-cyanocyclohexyl)phenyl]-3-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-6-bromo-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2,3-dihydro-1H-inden-5-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-6-bromo-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(2,3-dihydro-1H-inden-5-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-naphthalen-2-yl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-naphthalen-2-yl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(3,4,5-trichlorophenyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-2-(3,4,5-trichlorophenyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[3-chloro-4-(1-cyano-1-methylethyl)phenyl]-3-(2,3-dihydro-,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[3-chloro-4-(1-cyano-1-methylethyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-6-bromo-2-(3-chloro-4-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-6-bromo-2-(3-chloro-4-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-7-bromo-2-(3-chloro-4-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-7-bromo-2-(3-chloro-4-methylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,4-dihydro-1H-isochromen-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-(3,4-dihydro-1H-isochromen-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(3-chloro-4-cyclohexylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(3-chloro-4-cyclohexylphenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(3,4-dihydro-2H-chromen-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(3,4-dihydro-2H-chromen-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-7-bromo-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-7-bromo-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-7-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-7-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-7-(benzyloxy)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-7-(benzyloxy)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-7-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-7-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[3-chloro-4-(1-cyanocyclopropyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[3-chloro-4-(l-cyanocyclopropyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[3-chloro-4-(1-cyanocyclopropyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[3-chloro-4-(1-cyanocyclopropyl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4′-acetamido-[1,1-biphenyl]-4-yl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4′-acetamido-[1,1′-biphenyl]-4-yl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4′-acetamido-2-chloro-[1,1′-biphenyl]-4-yl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4′-acetamido-2-chloro-[1,1′-biphenyl]-4-yl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-methyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-N,N-dimethyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-N,N-dimethyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3R,4R)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-7-vinyl-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-oxo-7-vinyl-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dithiin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(ter-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dithiin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-7-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6 yl)-N-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-hydroxyl-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(chroman-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(chroman-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(4-isopropyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(4-isopropyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(3-cyclopropyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(3-cyclopropyl-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]oxathiin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

2-((3S,4S)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl)acetic acid;

2-((3R,4R)-2-(4-(tert-butyl)-3-chlorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl)acetic acid;

(3R,4R)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((S)-6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3R,4R)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((R)-6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid;

(3S,4S)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((S)-6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid; and

(3S,4S)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((R)-6-(hydroxymethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid.

16. The pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition according to claim 16 , further comprising one or more other therapeutic agents.

18. A method for the treatment of a STING-mediated disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

19. A method of treating a condition in a mammal that can be ameliorated by the selective inhibition of STING which condition is selected from: arthritis, asthma and obstructive airways diseases, autoimmune diseases or disorders, and cancer comprising administering to the mammal in need of such treatment, a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

20. The method according to claim 19 , wherein said condition is arthritis.

21. The method according to claim 20 , wherein said condition is selected from rheumatoid arthritis, juvenile arthritis, and psoriatic arthritis.

22. The method according to claim 19 , wherein said condition is asthma or obstructive airways diseases.

23. The method according to claim 22 , wherein said condition is selected from: chronic asthma, late asthma, airway hyper-responsiveness, bronchitis, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, dust asthma, recurrent airway obstruction, and chronic obstruction pulmonary disease (COPD), and emphysema.

24. The method according to claim 19 , wherein said condition is asthma.

25. The method according to claim 19 , wherein said condition is cancer.