IDO inhibitors

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient, diluent, or carrier, and a compound according to the formula,

a tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein

R 1 and R 4 are each hydrogen

and

R 5 is

wherein

R 13 is hydrogen or —SH; and

R 11 is —C 1 -C 6 alkyl-R A1 , -Q-(C 1 -C 6 )alkyl-R A1 , —C 1 -C 6 alkyl-Q-R A1 , -Q-(C 1 -C 6 )alkyl-Q-R A1 , —C 1 -C 6 alkyl-Q-(C 1 -C 6 )alkyl-R A1 , -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-R A1 , or -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-QR A1 ;

R 12 and R 14 are each independently hydrogen or halogen; and

R 15 is hydrogen;

wherein

each Q is independently —C(R A2 ) 2 —, —O—, —N(R A2 )—, —S—, —C(O)—, —S(O)—, —S(O) 2 —, —C(O)N(R A2 )—, —N(R A2 )C(O)—, or —CO)O—, wherein each R A2 is independently hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl;

R A1 is C 3 -C 8 cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted by 1, 2, 3, or 4 R A3 groups, wherein

each R A3 is independently halogen, cyano, nitro, —OR, —SR, —NR 2 , —C(O)R, —C(O)OR, —C(O)NR 2 , —S(O)R, —S(O) 2 R, —S(O)OR, —S(O) 2 OR, —S(O)NR 2 , —S(O) 2 NR 2 , —OC(O)R, —OC(O)OR, —OC(O)NR 2 , —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)NR 2 , —N(R)S(O)R, —N(R)S(O) 2 R, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 8 cycloalkyl, heterocyclyl, or aryl, wherein the cycloalkyl, heterocyclyl, aryl are each optionally substituted with 1, 2, 3, or 4 groups which are each independently R 30 or —C 1 -C 6 alkyl-R 30 , wherein R 30 is halogen, cyano, nitro, —OR A11 , —SR A11 , —N(R A11 ) 2 , —C(O)OR A11 , —C(O)N(R A11 ) 2 , —C(O)R A11 , —S(O)R A11 , —S(O) 2 R A11 , —S(O)O R A11 , —S(O) 2 OR A11 , —S(O)N(R A11 ) 2 , —S(O) 2 N(R A11 ) 2 , OC(O)R A11 , —OC(O)OR A11 , —OC(O)N(R A11 ) 2 , —N(R A11 )C(O)R A11 , —N(R A11 )C(O)OR A11 , —N(R A11 )C(O)N(R A11 ) 2 , —N(R A11 )S(O)R A11 , —N(R A11 )S(O) 2 R A11 , C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl, wherein each R A11 is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C 3 -C 8 cycloalkyl(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, or heteroaryl(C 1 -C 6 )alkyl,

or R A1 and R A2 taken together, when attached to the same carbon atom, form ═C 3 -C 8 cycloalkyl, or =heterocyclyl, wherein the cycloalkyl and heterocyclyl are optionally substituted with 1, 2, 3, or 4 groups which are each independently halogen, cyano, nitro, —OR, —SR, —NR 2 , —C(O)OR, —C(O)NR 2 , —C(O)R, —S(O)R, —S(O) 2 R, —S(O)OR, —S(O) 2 OR, —S(O) NR 2 , —S(O) 2 NR 2 , —OC(O)R, —OC(O)OR, —OC(O)NR 2 , —N(R)C(O)R, —N(R)C(O)OR, —N(R)C(O)NR 2 , —N(R)S(O)R, —N(R)S(O) 2 R, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl; and

each R is independently hydrogen or R 2 , wherein R 2 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C 3 -C 8 cycloalkyl(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, or heteroaryl(C 1 -C 6 )alkyl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkylalkyl, heterocyclylalkyl, arylalkyl, and heteroarylalkyl are each optionally substituted with 1, 2, 3, or 4 groups which are each independently halogen, cyano, nitro, —OR 10 , —SR 10 , —N(R 10 ) 2 , —C(O)OR 10 , —C(O)N(R 10 ) 2 , —C(O)R 10 , —S(O)R 10 , —S(O) 2 R 10 , —S(O)OR 10 , —S (O) 2 OR 10 , —S(O)N(R 10 ) 2 , —S(O) 2 N(R 10 ) 2 , —OC(O)R 10 , —OC(O)OR 10 , —OC(O)N(R 10 ) 2 , —N(R 10 )C(O)R 10 , —N(R 10 )C(O)OR 10 , —N(R 10 )C(O)N(R 10 ) 2 , —N(R 10 )S(O)R 10 , —N(R 10 )S(O) 2 R 10 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each R 10 is independently hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C 3 -C 8 cycloalkyl(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, or heteroaryl(C 1 -C 6 )alkyl,

wherein C 3 -C 8 cycloalkyl is cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, bicyclo[3.1.1]heptane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane or bicyclo[4.2.1]nonane.

2. A pharmaceutical composition wherein the compound is

4-(4-chloro-2-(4-chlorobenzyloxy)phenyl)-1H-imidazole;

4-(2-(2-bromophenethoxy)phenyl)-1H-imidazole;

4-(2-(2-(2-chlorophenoxy)ethyl)phenyl)-1H-imidazole;

3-(2-chlorophenethoxy)-2-(1H-imidazol-5-yl)phenol;

5-(2-(4-chlorobenzyloxy)phenyl)-1H-imidazole;

4-(2-(2-chlorophenethoxy)phenyl)-1H-imidazole;

4-(2-(2-cyclohexylethoxy)phenyl)-1H-imidazole;

5,5′-(2,2′-(3,3-dimethylpentane-1,5-diyl)bis(oxy)bis(2,1-phenylene))bis(1H-imidazole);

5-(2-(2-cyclopentylethoxy)phenyl)-1H-imidazole;

4-(2-phenethoxyphenyl)-1H-imidazole;

5-(2-(3-chlorobenzyloxy)phenyl)-1H-imidazole;

N-(2-(1H-imidazol-4-yl)benzyl)-2-chlorobenzamide;

4-(2-(3-chlorophenethoxy)phenyl)-1H-imidazole;

N-(4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)phenyl)acetamide;

4-(2-(2-methylbenzyloxy)phenyl)-1H-imidazole;

N-(3-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)phenyl)acetamide;

4-(2-((2-chlorobenzyloxy)methyl)phenyl)-1H-imidazole;

5-(2-(3-phenylpropoxy)phenyl)-1H-imidazole;

4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)-N-methylbenzamide;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzenesulfonamide;

4-(2-(benzyloxy)phenyl)-1H-imidazole;

5-(2-(3-methylbenzyloxy)phenyl)-1H-imidazole;

4-(5-bromo-2-(4-chlorobenzyloxy)phenyl)-1H-imidazole;

3-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)-N-methylbenzamide;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzonitrile;

4-(3-bromo-2-(4-chlorobenzyloxy)phenyl)-1H-imidazole;

4-(2-(4-chlorophenethoxy)phenyl)-1H-imidazole;

N-(4-chlorobenzyl)-2-(1H-imidazol-4-yl)aniline;

4-(2-(4-methylbenzyloxy)phenyl)-1H-imidazole;

3-(4-chlorobenzyloxy)-2-(1H-imidazol-5-yl)phenol;

3-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzonitrile;

4-(2-(2-chlorobenzyloxy)phenyl)-1H-imidazole;

3-((2-(1H-imidazol-4-yl)phenoxy)methyl)piperidine;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)-1-(methylsulfonyl)piperidine;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzamide ;

N-(3-(2-(1H-imidazol-5-yl)phenoxy)propyl)pyrimidin-2-amine;

2-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzonitrile ;

1-(4-((2-(1H-imidazol-4-yl)phenoxy)methyl)p iperidin-1-yl)ethanone;

N-(2-(2-(1H-imidazol-5-yl)phenoxy)ethyl)pyrimidin-2-amine;

1-(3-((2-(1H-imidazol-4-yl)phenoxy)methyl)piperidin-1-yl)ethanone;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzamide;

4-(4-chloro-2-(4-chlorobenzyloxy)phenyl)-1H-imidazole;

4-(2-(2-bromophenethoxy)phenyl)-1H-imidazole;

4-(2-(2-(2-chlorophenoxy)ethyl)phenyl)-1H-imidazole;

tert-butyl 4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)piperidine-1-carboxylate;

1-(4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)piperidin-1-yl)ethanone;

tert-butyl 2-(1H-imidazol-4-yl)phenylcarbamate;

N-(4-((2-(1H-imidazol-4-yl)phenoxy)methyl)benzyl)acetamide;

4-((2-(1H-imidazol-4-yl)phenoxy)methyl)piperidine;

4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)phenol;

2-(2-(1H-imidazol-4-yl)phenoxy)-2,3-dihydro-1H-inden-1-one;

4-(5-(2-(1H-imidazol-4-yl)phenoxy)-3,3-dimethylpentyl)morpholine;

3-(5-(2-(1H-imidazol-4-yl)phenoxy)-3,3-dimethylpentyl)-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-fluoropyrimidine-2,4(1H,3H)-dione;

5-(2-(5-(1H-imidazol-1-yl)-3,3-dimethylpentyloxy)phenyl)-1H-imidazole;

N-(5-(2-(1H-imidazol-5-yl)phenoxy)-3,3-dimethylpentyl)pyridin-4-amine;

N-(2-(2-(2-(1H-imidazol-4-yl)phenoxy)ethyl)phenyl)acetamide;

5-(2-(1H-imidazol-4-yl)phenoxy)-N-benzyl-3,3-dimethylpentan-1-amine;

4-(2-(2-(1H-imidazol-4-yl)phenoxy)ethylidene)cyclohexanecarboxamide;

4-((2-(1H-imidazol-5-yl)phenoxy)methyl)-7-methoxy-2H-chromen-2-one;

3-(2-(2-(1H-imidazol-5-yl)phenoxy)ethyl)-1H-indole;

2-(2-(1H-imidazol-5-yl)phenoxy)-N-(5,7-difluorobenzo[d]thiazol-2-yl)acetamide;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(4-(pyrrolidin-1-yl)phenyl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-N-(2-chlorophenyl)acetamide;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(benzofuran-2-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(thiazol-2-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(benzofuran-5-yl)ethanone;

2-(3-(2-(1H-imidazol-5-yl)phenoxy)propyl)isoindoline-1,3-dione;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(4-(diethylamino)phenyl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(thiophen-3-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(thiophen-2-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(benzofuran-3-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(pyridin-2-yl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(pyridin-4-yl)ethanone;

1-(2-(2-(1H-imidazol-5-yl)phenoxy)ethyl)-1H-pyrazole;

2-(2-(1H-imidazol-5-yl)phenoxy)-N-(thiophen-2-ylmethyl)acetamide;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(benzo[b]thiophen-5-yl)ethanone;

2-(4-(2-(1H-imidazol-5-yl)phenoxy)butyl)isoindoline-1,3-dione;

2-(2-(2-(1H-imidazol-5-yl)phenoxy)ethyl)isoindoline-1,3-dione;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(3-phenylisoxazol-5-yl)ethanone;

5-(2-(phenylsulfonylmethoxy)phenyl)-1H-imidazole;

5-(2-(2-(2,3-dihydrobenzofuran-5-yl)ethoxy)phenyl)-1H-imidazole;

2-(2-(1H-imidazol-5-yl)phenoxy)-N-(furan-2-ylmethyl)acetamide;

5-(2-(1-phenylpropan-2-yloxy)phenyl)-1H-imidazole;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(4-(methylsulfonyl)phenyl)ethanone;

3-(2-(1H-imidazol-5-yl)phenoxy)-1-phenylpyrrolidin-2-one;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(2,4-dihydroxyphenyl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-N-phenylpropanamide;

4-(2-(2-(1H-imidazol-5-yl)phenoxy)ethyl)-3,5-dimethyl-1H-pyrazole;

3-(2-(2-(1H-imidazol-5-yl)phenoxy)acetyl)-2H-chromen-2-one;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(2-hydroxyphenyl)ethanone;

2-(2-(1H-imidazol-5-yl)phenoxy)-2,3-dihydro-1H-inden-1-one;

5-(2-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methoxy)phenyl)-1H-imidazole;

2-(2-(1H-imidazol-5-yl)phenoxy)-1-(4-(difluoromethoxy)phenyl)ethanone;

5-(2-(1H-imidazol-5-yl)phenoxy)-6,7-dihydrobenzo[c][1,2,5]oxadiazol-4(5H)-one;

5-(2-(2-(1H-pyrrol-1-yl)ethoxy)phenyl)-1H-imidazole;

3-(2-(2-(1H-imidazol-5-yl)phenoxy)acetyl)benzoic acid;

2-((2-(1H-imidazol-5-yl)phenoxy)methyl)-1H-benzo[d]imidazole;

6-(2-(2-(1H-imidazol-5-yl)phenoxy)acetyl)-2H-benzo[b][1,4]oxazin-3(4H)-one;

6-(2-(2-(1H-imidazol-5-yl)phenoxy)acetyl)benzo[d]oxazol-2(3H)-one;

1-(3-(2-(1H-imidazol-5-yl)phenoxy)propyl)-4-(3-chlorophenyl)piperazine;

2-((2-(1H-imidazol-5-yl)phenoxy)methyl)pyridine;

5-((2-(1H-imidazol-5-yl)phenoxy)methyl)-2-chloropyridine;

4-((2-(1H-imidazol-5-yl)phenoxy)methyl)pyridine;

2-((2-(1H-imidazol-5-yl)phenoxy)methyl)quinazolin-4(3H)-one;

2-((2-(1H-imidazol-5-yl)phenoxy)methyl)quinoline;

3-((2-(1H-imidazol-5-yl)phenoxy)methyl)quinoxalin-2(1H)-one;

3-((2-(1H-imidazol-5-yl)phenoxy)methyl)benzo[d]thiazol-2(3H)-one;

ethyl 2-(2-(2-(2-(1H-imidazol-5-yl)phenoxy)acetamido)thiazol-4-yl)acetate;

5-(2-(naphthalen-2-ylmethoxy)phenyl)-1H-imidazole;

5-(2-(2-(naphthalen-1-yl)ethoxy)phenyl)-1H-imidazole;

or a pharmaceutically acceptable salt thereof.

3. The pharmaceutical composition of claim 1 , wherein

(i) R 11 is —C 6 alkyl-R A1 , -Q-(C 1 -C 6 )alkyl-R A1 , —C 1 -C 6 alkyl-Q-

R A1 , -Q-(C 1 -C 6 )alkyl-Q-R A1 , C 1 -C 6 -alkyl-Q-(C 1 -C 6 )alkyl-R A1 , -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-R A1 , or -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-QR A1 ,

or

and R 12 and R 14 is halogen,

and

(ii) R 13 is hydrogen or —SH.

4. The pharmaceutical composition of claim 3 , wherein R 11 is —C 1 -C 6 alkyl-R A1 , -Q-(C 1 -C 6 )alkyl-R A1 , —C 1 -C 6 alkyl-Q-R A1 , -Q-(C 1 -C 6 )alkyl-Q-R A1 , —C 1 -C 6 alkyl-Q-(C 1 -C 6 )alkyl-R A1 , -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-R A1 , or -Q(C 1 -C 6 )alkyl-Q-(C 1 -C 6 )alkyl-QR A1 .

5. The pharmaceutical composition of claim 3 , wherein R 11 is —C 1 -C 6 alkyl-R A1 , -Q-(C 1 -C 6 )alkyl-R A1 , —C 1 -C 6 alkyl-Q-R A1 , -Q-(C 1 C 6 )alkyl-C(R A2 ) 2 —R A1 , or —(C 1 -C 6 )alkyl-Q-C 1 -C 6 alkyl-R A1 , or -Q(C 1 -C 6 )alkyl-C(R A2 ) 2 —(C 1 -C 6 )alkyl-Q-R A1 , wherein each is Q is independently —O—, —N(R A2 )—, or —S—.

6. The pharmaceutical composition of claim 3 , wherein

R 12 and R 14 are halogen

and

R 13 is hydrogen or —SH.

7. The pharmaceutical composition of claim 3 , wherein R 13 is hydrogen or —SH, and at least one of R 12 and R 14 is fluoro, chloro, bromo, methyl, or ethyl.