AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES

摘要

Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.;

主权项

1. A compound having the following formula I:or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein:
Y is N or CR6; R1 is selected from H and C1-3alkyl or C3-6cycloalkyl, each optionally substituted by 0-7 R1a; R1a at each occurrence is independently hydrogen, deuterium, F, Cl, Br or CN; R2 is —C(O)R2a; or C1-6alkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 R2a or a 5-14 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, each group substituted with 0-4 R2a; R2a at each occurrence is independently hydrogen, ═O, halo, OCF3, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)pRc, C1-6 alkyl substituted with 0-3 Ra, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, C2-6 alkynyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra or a —(CH2)r-5-7 membered heterocycle comprising carbon atoms or 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra; R3 is C3-10 cycloalkyl, C6-10 aryl or a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, each group substituted with 0-4 R3a; R3a at each occurrence is independently hydrogen, ═O, halo, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)pRc, C1-6 alkyl substituted with 0-3 Ra, C2-6 alkenyl substituted with 0-3 Ra, C2-6 alkynyl substituted with 0-3 Ra, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-3 Ra or a —(CH2)r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Ra; or two R3a, 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 Ra1; R4 and R5 are independently hydrogen, C1-4 alkyl substituted with 0-1 Rf, (CH2)r-phenyl substituted with 0-3 Rd or a —(CH2)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p; R6 is hydrogen, halo, C1-4alkyl, C1-4haloalkyl, OC1-4haloalkyl, OC1-4alkyl, CN, NO2 or OH; R11 at each occurrence is independently hydrogen, C1-4 alkyl substituted with 0-3 Rf, CF3, C3-10 cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd; Ra and Ra1 at each occurrence are independently hydrogen, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-3 Rf, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, C2-6 alkynyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf; Rb is hydrogen, C1-6 alkyl substituted with 0-3 Rd, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rd; Rc is C1-6 alkyl substituted with 0-3 Rf, (CH2)r—C3-6 cycloalkyl substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rf; Rd at each occurrence is independently hydrogen, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rc, —NReRe, —NReC(O)ORc, C1-6 alkyl or (CH2)r-phenyl substituted with 0-3 Rf; Re at each occurrence is independently selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl and (CH2)r-phenyl substituted with 0-3 Rf; Rf independently at each occurrence is hydrogen, halo, CN, NH2, OH, C3-6 cycloalkyl, CF3, O(C1-6alkyl) or a —(CH2)r-5-7 membered heterocycle comprising carbon atoms and 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.