Claims for Patent: 10,000,480

Summary for Patent: 10,000,480

Title:	Amide-substituted heterocyclic compounds useful as modulators of IL-12, IL-23 and/or IFN alpha responses
Abstract:	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.
Inventor(s):	Ryan M. Moslin, David S. Weinstein, Stephen T. Wrobleski, John S. Tokarski, Amit Kumar, Douglas G. Batt, Shuqun Lin, Chunjian Liu, Steven H. Spergel, Yanlei Zhang, Qingjie Liu
Assignee:	Syngene International Ltd , Bristol Myers Squibb Co
Application Number:	US15/289,437
Patent Claims:	1. A compound having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein: Y is N or CR6; R1 is hydrogen, 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, 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 containing 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 containing 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 containing 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 containing 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 containing 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 containing 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 hydrogen, C1-6 alkyl, C3-6 cycloalkyl or (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 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 R2 is —C(O)R2a; or C1-6alkyl, C3-6cycloalkyl, phenyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl or pyrrolopyridinyl, each group substituted with 0-4 R2a. 3. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein both R4 and R5 are hydrogen. 4. A compound according to claim 1, having the following formulae: or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein: R1 is hydrogen or C1-3alkyl substituted by 0-7 R1a; R1a at each occurrence is independently hydrogen, deuterium or halogen; R2 is —C(O)R2a; or C1-6alkyl, C3-6cycloalkyl, phenyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, quinolinyl or pyrrolopyridinyl, each group substituted with 0-4 R2a; R2a at each occurrence is independently hydrogen, ═O, halo, CN, —(CH2)rORb, —(CH2)rC(O)Rb, —NRbC(O)Rc, —C(O)ORb, —(CH2)rC(O)NR11R11, —S(O)pNR11R11, —C1-6alkyl substituted with 0-3 Ra, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra or a —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra; R3 is C3-10 cycloalkyl, a 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, halo, OCF3, CF3, CHF2, CN, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)pRc, C1-6 alkyl substituted with 0-3 Ra, C1-6 haloalkyl, a —(CH2)r-3-14 membered carbocycle substituted with 0-3 Ra or a —(CH2)r-5-10 membered heterocycle containing 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 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 Ra; R11 at each occurrence is independently hydrogen, C1-4 alkyl substituted with 0-3 Rf or C3-6cycloalkyl substituted with 0-1 Rf; Ra at each occurrence is hydrogen, ═O, F, —(CH2)rORb or C1-6alkyl 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 containing 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 or C3-6 cycloalkyl, each group substituted with 0-3 Rf; Rd at each occurrence is independently hydrogen, F, Cl, Br or —OH; Rf at each occurrence is independently hydrogen, halo, CN, OH or O(C1-6alkyl); 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 R2 is pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl or quinolinyl, each group substituted with 0-3 R2a. 6. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R2 is —C(O)R2a; or C1-6alkyl, C3-6cycloalkyl or phenyl substituted with 0-3 R2a. 7. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R2 is: 8. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R3 is phenyl, cyclopentyl, cyclohexyl, triazolyl, oxadiazolyl, pyrimidinyl, tetrazolyl, pyrazolyl, thiazolyl, furanyl, or pyranyl, each group substituted with 0-4 R3a. 9. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein: R3a at each occurrence independently is hydrogen, phenyl, CN, NH2, OCF3, ORb, halo, cycloalkyl, C(O)NR11R11, S(O)2NR11R11, C(O)Rb, SOpRc, NRbSOpRc, NRbC(O)Rc, haloalkyl, CN, 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O substituted with 0-3 Ra and C1-6 alkyl substituted with 0-3 Ra; or one R3a and a second R3a, 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; R11 at each occurrence independently is hydrogen, C3-6 cycloalkyl substituted with 0-3 Rf, or C1-4alkyl substituted with 0-1 Rf; Ra independently at each occurrence is C1-6 alkyl substituted with 0-3 Rf, halo (F) or ORb; Rb independently at each occurrence is hydrogen, 5-7 membered heterocycle containing 1-4 heteroatoms selected from N, S or O substituted with 0-3 Rf, or C1-6 alkyl substituted with 0-3 Rd; Rd independently at each occurrence is F, Cl, Br or OH; Rc independently at each occurrence is C1-6 alkyl or C3-6 cycloalkyl, each group substituted with 0-3 Rf; Rf 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: R3 is R3aa is S(O)pRc, ORb, Cl, F, CN, NH2, C(O)NR11R11, NRbSOpRc, NRbC(O)Rc, C1-6 alkyl substituted with 0-3 Ra or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms selected from N, O, and S substituted with 0-3 R3a; R3ab, R3ac, or R3ad are independently hydrogen, Cl, F, Br, CN, ORb, C1-6 alkyl substituted with 0-3 Ra; C(O)NR11R11, C(O)Rb, S(O)pRc, or a 4-7 membered heterocycle containing 1-3 heteroatoms selected from N, O, and S substituted with 0-3 Ra; R11 at each occurrence independently is hydrogen, cyclopropyl substituted with 0-3 Rf or C1-4alkyl substituted with 0-3 Rf; Ra at each occurrence independently is C1-6 alkyl substituted with 0-3 Rf, ORb or halo; Rb at each occurrence independently is hydrogen, C1-6 alkyl substituted with 0-2 Rd or a 5- to 7-membered heterocycle containing 1-3 heteroatoms selected from N, O and S; Rc at each occurrence independently is C1-6 alkyl substituted with 0-3 Rf; Rd at each occurrence independently is F or OH; Rf 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 R3aa is S(O)pRc or C(O)NR11R11. 12. A compound according claim 10, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R3aa is ORb. 13. A compound according to claim 1, or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R3 is: 14. A pharmaceutical composition comprising one or more compounds according to claim 1, and a pharmaceutically acceptable carrier or diluent.