HETEROCYCLIC COMPOUNDS COMPRISING PYRIDINE USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSESCompounds 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.A compound of formula I:wherein X is N or CH;R1 is selected from H, CD3, C1-3 alkyl or C3-6 cycloalkyl;R2 is -C(0)R2a; C1-6 alkyl, -(CH?.)r-3-14 membered carbocycle substituted with 0-1 R2a or a 5-12 membered heterocycle containing 1 -4 heteroatoms selected from N, O, and S, substituted with 0-4 R2a; R2a at each occurrence is independently H, OCF3, CN, NO?., -(CH?)rORb,-(CH2)rSRb, -(CH2) C(0)Rb, -(CH2)rC(0)ORb, -(CH2 OC(0)Rb, CHrlrNR^R11,-(CH2)rC (0)NR'! 1 R11 , ~(CH2)rNRbC(0)Rc, ~(CH2)rNRbC(0)QRc, -NRhC{()) R! ! RM. -S OipNR1^11, -NRbS(0)pRc, -S(0)PRc, Ci-6 alkyl substituted with 0-3 R3, Cue haloalkyl, C2-6 alkenyl substituted with 0-3 R3, -(CH2)f-3-l4 membered carbocycle substituted with 0-1 R3 or a -(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(0)P substituted with 0-2 R3;R3 is H, Ci-3 alkyl or C3-6 cycloalkykR4 is H, C1-3 alkyl or C3-6 cycloalkyl;R5 is Ci -4 alkyl substituted with 0-1 R5a, C1-4 alkoxy substituted with 0-1 R53, (CH2)r..phenyl substituted with 0-3 R5a or a ~(CH2)~5~7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(0)P;R5,3 is is independently at each occurrence, H, F, Cl, Br, OCF3, CFs, CN,NO?, -ORe, -(CH2)rC(0)Rc, -NReRe, -NReC(0)ORc, C1-6 alkyl or (CH )r-phenyl substituted with 0-3 Rf; R6 is Ci -4 alkyl substituted with 0-1 R6a, (CH2)r-phenyl substituted with 0-3 R6a or a -(CH2)-5-7 rnerabered heterocyele containing 1 -4 heteroatoms selected from N, O, and S(0)P substituted with 0-3 Rba;R6a is H, Ci-4 alkyl substituted with 0-3 Rf, CFN, C ?3-J O cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or -(CH2)r-5-7 membered heterocyele containing 1-4 heteroatoms selected from N. O, and S(0)p substituted with 0-3 Rd;R7 is H, Ci-3 alkyl or Ci-6 cycloalkyl;RH at each occurrence is independently H, Ci-4 alkyl substituted with 0-3 Rf, CFy C3-10 cycloalky] substituted with 0-1 Rf, (CH)r-pheny] substituted with 0-3 Rd or -(CH2)r~5-7 membered heterocyele containing 1-4 heteroatoms selected from N, O, and S(0)P substituted with 0-3 Rd:Ra at each occurrence is independently H, F. Cl, Br, OCFs, CF3, CHF2, CN, alkyl substituted with 0-3 R1, C1-6 haloalkyl, C2-e alkenyl substituted with 0-3 Ra, C2-e alkynyl substituted ith 0-3 R3, -(CH2)r-3-14 membered carbocycle or ~(CH2)r-5-7 membered heterocyele containing 1-4 heteroatoms selected from N, O, and S(0)P substituted with 0-3 Rf;Rb is H, Ci-6 alkyl substituted with 0-3 Rd, Ci-e. haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or -(CH2)r-5-7 membered heterocyele containing 1-4 heteroatoms selected from N, O, and S(0)P substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rd;Rc is Ci-6 alkyl substituted with 0-3 R1, (CH2)r~C3-6 cycloalkyl substituted with 0-3 R1 or (CH2)r-phenyI substituted with 0-3 R1;Rd is independently at each occurrence, hydrogen, F, Cl, Br, OCF3, CF3, CN, N02, -ORe, -(CH2)rC(0)Rc, -NReRe, -NReC(0)ORc, Ci-e alkyl or (CH2)r-phenyl substituted with 0-3 Rf;Re is independently at each occurrence, hydrogen, Ci-6 alkyl, C3-6 cycloalkyl or (CH2)r-phenyl substituted with 0-3 Rf; Rf is independently at each occurrence, hydrogen, halo, CN, NH2, OH, C3-6 cycloalkyl, CF3, 0(Ci-6 alkyl) or a -(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(0)P;p is 0, 1, or 2;r is 0, 1, 2, 3, or 4;or a stereoisomer or pharmaceutically acceptable salt thereof.The compound according to claim 1 of the formula whereinX is N or CH;R1 is selected from H, CDs, CM alkyl or C3-6 cycloalkyl;R2 is -C(0)R a; Cue alkyl, -(CH2)r-3-14 membered carbocycle substituted with 0-1 R2a or a 5-12 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R2a;R2a at each occurrence is independently H, OCF3, CN, NO?., -(CH2)rORb,-(CH?)rSRb, -(CH?)rC(0)Rb, -(CH?)rC(0)0Rb, -(CH?)rOC(0)Rb, CH2)rNR11R11,-(( i l ' 'CO) : : Rn. -(CH?)rNRbC (0)RC, -(CH2)rNRbC(0)0Rc, -NRbC(0)NRiiR11, -S(0)pNR!1R11, -NRbS(0)pRc, -S(0)PRc, CM alkyl substituted with 0-3 Ra, C1 -6 haloalkyi, C2-6 alkenyl substituted with 0-3 Ra, -(CH2)r-3-I4 membered carbocycle substituted with 0-1 R3 or a ~(CH2)r-5-7 membered heterocycle containing 1 -4 heteroatoms selected from N, O, and S(0)P substituted with 0-2 R3;RJ is H, Ci-3 alkyl or C3-6 cycloaikykR4 is H, C1-3 alkyl or C3-6 cycloalkyl; R5 is Ci -4 alkyl substituted with 0-1 R5a, Ci-4 alkoxy substituted with 0-1 R5a, (CH2)r-phenyl substituted with 0-3 R5a or a -(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(0)P;R3a is is independently at each occurrence, H, F, Cl, Br, OCF3, CF3, CN,NO2, -ORe, -(CH2)rC(0)Rc, -NReRe, -NReC(0)ORc, Ci-e alkyl or (CH2)r-phenyl substituted with 0-3 Rf;R6 is Ci-4 alkyl substituted with 0-1 Rba, (CFh)r-phenyl substituted with 0-3 Rba or a -(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected fromN, O, and S(0)P substituted with 0-3 RM;R6a is H, Ci-4 alkyl substituted with 0-3 R1, CFs, C3-10 cyc!oalkyl substituted with 0-1 Rf, (C...
IL-12, IL-23 및/또는 IFN 알파 반응의 조정제로서 유용한 피리딘을 포함하는 헤테로시클릭 화합물하기 화학식 I을 갖는 화합물: 또는 그의 입체이성질체 또는 제약상 허용되는 염 (여기서 R1, R2, R3, R4, 및 R5는 본원에 정의된 바와 같음)은, Tyk-2에 작용하여 신호 전달 억제를 유발함으로써 IL-12, IL-23 및/또는 IFNα의 조절에 유용하다.화학식 I의 화합물 또는 그의 입체이성질체 또는 제약상 허용되는 염.여기서X는 N 또는 CH이고;R1은 H, CD3, C1-3 알킬 또는 C3-6 시클로알킬로부터 선택되고;R2는 -C(O)R2a; C1-6 알킬, 0-1개의 R2a로 치환된 -(CH2)r-3-14원 카르보사이클, 또는 0-4개의 R2a로 치환된, N, O 및 S로부터 선택된 1-4개의 헤테로원자를 함유하는 5-12원 헤테로사이클이고;R2a는 각 경우에 독립적으로 H, 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, 0-3개의 Ra로 치환된 C1-6 알킬, C1-6 할로알킬, 0-3개의 Ra로 치환된 C2-6 알케닐, 0-1개의 Ra로 치환된 -(CH2)r-3-14원 카르보사이클, 또는 0-2개의 Ra로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클이고;R3은 H, C1-3 알킬 또는 C3-6 시클로알킬이고; R4는 H, C1-3 알킬 또는 C3-6 시클로알킬이고;R5는 0-1개의 R5a로 치환된 C1-4 알킬, 0-1개의 R5a로 치환된 C1-4 알콕시, 0-3개의 R5a로 치환된 (CH2)r-페닐, 또는 N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)-5-7원 헤테로사이클이고;R5a는 각 경우에 독립적으로 H, F, Cl, Br, OCF3, CF3, CN, NO2, -ORe, -(CH2)rC(O)Rc, -NReRe, -NReC(O)ORc, C1-6 알킬, 또는 0-3개의 Rf로 치환된 (CH2)r-페닐이고;R6은 0-1개의 R6a로 치환된 C1-4 알킬, 0-3개의 R6a로 치환된 (CH2)r-페닐, 또는 0-3개의 R6a로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)-5-7원 헤테로사이클이고;R6a는 H, 0-3개의 Rf로 치환된 C1-4 알킬, CF3, 0-1개의 Rf로 치환된 C3-10 시클로알킬, 0-3개의 Rd로 치환된 (CH)r-페닐, 또는 0-3개의 Rd로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클이고;R7은 H, C1-3 알킬 또는 C3-6 시클로알킬이고;R11은 각 경우에 독립적으로 H, 0-3개의 Rf로 치환된 C1-4 알킬, CF3, 0-1개의 Rf로 치환된 C3-10 시클로알킬, 0-3개의 Rd로 치환된 (CH)r-페닐, 또는 0-3개의 Rd로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클이고;Ra는 각 경우에 독립적으로 H, 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, 0-3개의 Rf로 치환된 C1-6 알킬, C1-6 할로알킬, 0-3개의 Ra로 치환된 C2-6 알케닐, 0-3개의 Ra로 치환된 C2-6 알키닐, -(CH2)r-3-14원 카르보사이클, 또는 0-3개의 Rf로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클이고;Rb는 H, 0-3개의 Rd로 치환된 C1-6 알킬, C1-6 할로알킬, 0-2개의 Rd로 치환된 C3-6 시클로알킬, 또는 0-3개의 Rf로 치환된, N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클 또는 0-3개의 Rd로 치환된 (CH2)r-페닐이고;Rc는 0-3개의 Rf로 치환된 C1-6 알킬, 0-3개의 Rf로 치환된 (CH2)r-C3-6 시클로알킬, 또는 0-3개의 Rf로 치환된 (CH2)r-페닐이고;Rd는 각 경우에 독립적으로 수소, F, Cl, Br, OCF3, CF3, CN, NO2, -ORe, -(CH2)rC(O)Rc, -NReRe, -NReC(O)ORc, C1-6 알킬, 또는 0-3개의 Rf로 치환된 (CH2)r-페닐이고;Re는 각 경우에 독립적으로 수소, C1-6 알킬, C3-6 시클로알킬, 또는 0-3개의 Rf로 치환된 (CH2)r-페닐이고;Rf는 각 경우에 독립적으로 수소, 할로, CN, NH2, OH, C3-6 시클로알킬, CF3, O(C1-6 알킬), 또는 N, O 및 S(O)p로부터 선택된 1-4개의 헤테로원자를 함유하는 -(CH2)r-5-7원 헤테로사이클이고;p는 0, 1, 또는 2이고;r은 0, 1, 2, 3, 또는 4이다.