Amide-substituted heterocyclic compounds useful as modulators of IL-12, IL-23 and/or IFN alpha responses

1. A compound having the following formula I:

or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein:

Y is N or CR 6 ;

R 1 is hydrogen, C 1-3 alkyl or C 3-6 cycloalkyl, each optionally substituted by 0-7 R 1a ;

R 1a at each occurrence is independently hydrogen, deuterium, F, Cl, Br or CN;

R 2 is —C(O)R 2a ; or C 1-6 alkyl, —(CH 2 ) r -3-14 membered carbocycle substituted with 0-1 R 2a or a 5-14 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R 2a ;

R 2a at each occurrence is independently hydrogen, ═O, halo, OCF 3 , CN, NO 2 , —(CH 2 ) r OR b , —(CH 2 ) r SR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r C(O)OR b , —(CH 2 ) r OC(O)R b , CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —(CH 2 ) r NR b C(O)OR c , —NR b C(O)NR 11 R 11 , —S(O) p NR 11 R 11 , —NR b S(O) p R c , —S(O) p R c , C 1-6 alkyl substituted with 0-3 R a , C 1-6 haloalkyl, C 2-6 alkenyl substituted with 0-3 R a , C 2-6 alkynyl substituted with 0-3 R a , —(CH 2 ) r -3-14 membered carbocycle substituted with 0-1 R a or a —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-2 R a ;

R 3 is C 3-10 cycloalkyl, C 6-10 aryl or a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, each group substituted with 0-4 R 3a ;

R 3a at each occurrence is independently hydrogen, ═O, halo, OCF 3 , CF 3 , CHF 2 , CN, NO 2 , —(CH 2 ) r OR b , —(CH 2 ) r SR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r C(O)OR b , —(CH 2 ) r OC(O)R b , —(CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —(CH 2 ) r NR b C(O)OR c , —NR b C(O)NR 11 R 11 , —S(O) p NR 11 R 11 , —NR b S(O) p R c , —S(O) p R c , C 1-6 alkyl substituted with 0-3 R a , C 2-6 alkenyl substituted with 0-3 R a , C 2-6 alkynyl substituted with 0-3 R a , C 1-6 haloalkyl, —(CH 2 ) r -3-14 membered carbocycle substituted with 0-3 R a or a —(CH 2 ) r -5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R a ;

or two R 3a , together with the atoms to which they are attached, combine to form a fused ring wherein said ring is selected from phenyl and a heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O) p , each fused ring substituted with 0-3 R a1 ;

R 4 and R 5 are independently hydrogen, C 1-4 alkyl substituted with 0-1 R f , (CH 2 ) r -phenyl substituted with 0-3 R d or a —(CH 2 )-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p ;

R 6 is hydrogen, halo, C 1-4 alkyl, C 1-4 haloalkyl, OC 1-4 haloalkyl, OC 1-4 alkyl, CN, NO 2 or OH;

R 11 at each occurrence is independently hydrogen, C 1-4 alkyl substituted with 0-3 R f , CF 3 , C 3-10 cycloalkyl substituted with 0-1 R f , (CH) r -phenyl substituted with 0-3 R d or —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R d ;

R a and R a1 at each occurrence are independently hydrogen, F, Cl, Br, OCF 3 , CF 3 , CHF 2 , CN, NO 2 , —(CH 2 ) r OR b , —(CH 2 ) r SR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r C(O)OR b , —(CH 2 ) r OC(O)R b , —(CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —(CH 2 ) r NR b C(O)OR c , —NR b C(O)NR 11 R 11 , —S(O) p NR 11 R 11 , —NR b S(O) p R c , —S(O)R c , —S(O) 2 R c , C 1-6 alkyl substituted with 0-3 R f , C 1-6 haloalkyl, C 2-6 alkenyl substituted with 0-3 R a , C 2-6 alkynyl substituted with 0-3 R a , —(CH 2 ) r -3-14 membered carbocycle or —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R f ;

R b is hydrogen, C 1-6 alkyl substituted with 0-3 R d , C 1-6 haloalkyl, C 3-6 cycloalkyl substituted with 0-2 R d , or —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R f or (CH 2 ) r -phenyl substituted with 0-3 R d ;

R c is C 1-6 alkyl substituted with 0-3 R f , (CH 2 ) r —C 3-6 cycloalkyl substituted with 0-3 R f or (CH 2 ) r -phenyl substituted with 0-3 R f ;

R d at each occurrence is independently hydrogen, F, Cl, Br, OCF 3 , CF 3 , CN, NO 2 , —OR e , —(CH 2 ) r C(O)R c , —NR e R e , —NR e C(O)OR c , C 1-6 alkyl or (CH 2 ) r -phenyl substituted with 0-3 R f ;

R e at each occurrence is independently hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl or (CH 2 ) r -phenyl substituted with 0-3 R f ;

R f independently at each occurrence is hydrogen, halo, CN, NH 2 , OH, C 3-6 cycloalkyl, CF 3 , O(C 1-6 alkyl) or a —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p ;

p is 0, 1, or 2; and

r is 0, 1, 2, 3, or 4.

2. A compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is —C(O)R 2a ; or C 1-6 alkyl, C 3-6 cycloalkyl, phenyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl or pyrrolopyridinyl, each group substituted with 0-4 R 2a .

3. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein both R 4 and R 5 are hydrogen.

4. A compound according to claim 1 , having the following formulae:

or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein:

R 1 is hydrogen or C 1-3 alkyl substituted by 0-7 R 1a ;

R 1a at each occurrence is independently hydrogen, deuterium or halogen;

R 2 is —C(O)R 2a ; or C 1-6 alkyl, C 3-6 cycloalkyl, phenyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl or pyrrolopyridinyl, each group substituted with 0-4 R 2a ;

R 2a at each occurrence is independently hydrogen, ═O, halo, CN, —(CH 2 ) r OR b , —(CH 2 ) r C(O)R b , —NR b C(O)R c , —C(O)OR b , —(CH 2 ) r C(O)NR 11 R 11 , —S(O) p NR 11 R 11 , —C 1-6 alkyl substituted with 0-3 R a , C 1-6 haloalkyl, —(CH 2 ) r -3-14 membered carbocycle substituted with 0-1 R a or a —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-2 R a ;

R 3 is C 3-10 cycloalkyl, a C 6-10 aryl, or a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, each group substituted with 0-4 R 3a ;

R 3a at each occurrence is independently hydrogen, halo, OCF 3 , CF 3 , CHF 2 , CN, —(CH 2 ) r OR b , —(CH 2 ) r SR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —S(O) p NR 11 R 11 , —NR b S(O) p R c , —S(O) p R c , C 1-6 alkyl substituted with 0-3 R a , C 1-6 haloalkyl, a —(CH 2 ) r -3-14 membered carbocycle substituted with 0-3 R a or a —(CH 2 ) r -5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R a ;

or two R 3a , together with the atoms to which they are attached, combine to form a fused ring wherein that ring is phenyl or a 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O, each fused ring substituted, as valence allows, by 0-3 R a ;

R 11 at each occurrence is independently hydrogen, C 1-4 alkyl substituted with 0-3 R f or C 3-6 cycloalkyl substituted with 0-1 R f ;

R a at each occurrence is hydrogen, ═O, F, —(CH 2 ) r OR b or C 1-6 alkyl substituted with 0-3 R f ;

R b is hydrogen, C 1-6 alkyl substituted with 0-3 R d , C 1-6 haloalkyl, C 3-6 cycloalkyl substituted with 0-2 R d , or —(CH 2 ) r -5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O) p substituted with 0-3 R f ; or (CH 2 ) r -phenyl substituted with 0-3 R d ;

R c is C 1-6 alkyl or C 3-6 cycloalkyl, each group substituted with 0-3 R f ;

R d at each occurrence is independently hydrogen, F, Cl, Br or —OH;

R f at each occurrence is independently hydrogen, halo, CN, OH or O(C 1-6 alkyl);

p is 0, 1 or 2; and

r is 0, 1 or 2.

5. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl or quinolinyl, each group substituted with 0-3 R 2a .

6. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is —C(O)R 2a ; or C 1-6 alkyl, C 3-6 cycloalkyl or phenyl substituted with 0-3 R 2a .

7. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is:

8. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3 is phenyl, cyclopentyl, cyclohexyl, triazolyl, oxadiazolyl, pyrimidinyl, tetrazolyl, pyrazolyl, thiazolyl, furanyl, or pyranyl, each group substituted with 0-4 R 3a .

9. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein:

R 3a at each occurrence independently is hydrogen, phenyl, CN, NH 2 , OCF 3 , OR b , halo, cycloalkyl, C(O)NR 11 R 11 , S(O) 2 NR 11 R 11 , C(O)R b , SO p R c , NR b SO p R c , NR b C(O)R c , haloalkyl, CN, 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O substituted with 0-3 R a and C 1-6 alkyl substituted with 0-3 R a ; or

one R 3a and a second R 3a , together with the atoms to which they are attached, combine to form a fused 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O, or phenyl;

R 11 at each occurrence independently is hydrogen, C 3-6 cycloalkyl substituted with 0-3 R f , or C 1-4 alkyl substituted with 0-1 R f ;

R a independently at each occurrence is C 1-6 alkyl substituted with 0-3 R f , halo (F) or OR b ;

R b independently at each occurrence is hydrogen, 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O substituted with 0-3 R f , or C 1-6 alkyl substituted with 0-3 R d ;

R d independently at each occurrence is F, Cl, Br or OH;

R c independently at each occurrence is C 1-6 alkyl or C 3-6 cycloalkyl, each group substituted with 0-3 R f ;

R f independently at each occurrence is hydrogen, halo or OH; and

p is 2.

10. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein:

R 3 is

R 3aa is S(O) p R c , OR b , Cl, F, CN, NH 2 , C(O)NR 11 R 11 , NR b SO p R c , NR b C(O)R c , C 1-6 alkyl substituted with 0-3 R a or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, and S substituted with 0-3 R 3a ;

R 3ab , R 3ac , or R 3ad are independently hydrogen, Cl, F, Br, CN, OR b , C 1-6 alkyl substituted with 0-3 R a ; C(O)NR 11 R 11 , C(O)R b , S(O) p R c , or a 4-7 membered heterocycle containing 1-3 heteroatoms selected from N, O, and S substituted with 0-3 R a ;

R 11 at each occurrence independently is hydrogen, cyclopropyl substituted with 0-3 R f or C 1-4 alkyl substituted with 0-3 R f ;

R a at each occurrence independently is C 1-6 alkyl substituted with 0-3 R f , OR b or halo;

R b at each occurrence independently is hydrogen, C 1-6 alkyl substituted with 0-2 R d or a 5- to 7-membered heterocycle containing 1-3 heteroatoms selected from N, O and S;

R c at each occurrence independently is C 1-6 alkyl substituted with 0-3 R f ;

R d at each occurrence independently is F or OH;

R f at each occurrence independently is halo or OH; and

p is 0-2.

11. A compound according to claim 10 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3aa is S(O) p R c or C(O)NR 11 R 11 .

12. A compound according claim 10 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3aa is OR b .

13. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3 is:

14. A pharmaceutical composition comprising one or more compounds according to claim 1 , and a pharmaceutically acceptable carrier or diluent.