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US 9,540,333 B2Granted
Alkyl amide-substituted pyrimidine compounds useful in the modulation of IL-12, IL-23 and/or IFNα
AssigneeBristol-Myers Squibb Company
InventorsJoseph B. Santella, Ryan M. Moslin, David S. Weinstein, Stephen T. Wrobleski, John S. Tokarski
Life of this patent
Estimating the term…
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.
Claims16
A compound having the following formula (I):
- or a stereoisomer or pharmaceutically-acceptable sale thereof, wherein:
- R1 is C1-3alkyl optionally substituted by 0-7 R1a;
- R1a at each occurrence is independently hydrogen, deuterium, F, Cl, Br, CF3 or CN;
- R2 is —(CH2)r-3-14 membered carbocycle, each group substituted with 0-4 R2a;
- R2a at each occurrence is independently hydrogen, ═O, halo, OCF3, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(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, 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, —NRb S(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 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, S or O said fused ring further substituted by 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;
- 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, —NRb S(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 at each occurrence is independently 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, (CH2)r-phenyl substituted with 0-3 Rf, or
- Rd at each occurrence is independently hydrogen, F, Cl, Br, OCF3, CF3, CN, NO2, —ORc, —(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(C1-6 alkyl), or a —(CH2)r-5-7 membered heteroaryl 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.
16 more elements
A compound which is
- or a stereoisomer or pharmaceutically-acceptable salt thereof.
Dependencies are inferred from the claim text.