发明名称 HETEROCYCLIC-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS KINASE INHIBITORS
摘要 Compounds having the following formula: wherein A is, or; and X is N or C—R7, or an enantiomer, diastereomer or a pharmaceutically-acceptable salt thereof, are useful as kinase modulators, including IRAK-4 modulation.;
申请公布号 US2015011532(A1) 申请公布日期 2015.01.08
申请号 US201314371456 申请日期 2013.01.11
申请人 Bristol-Myers Squibb Company 发明人 Paidi Venkatram Reddy;Kumar Sreekantha Ratna;Banejee Abhisek;Sistla Ramesh;Nair Satheesh Kesavan;Pitts William J.;Hynes John
分类号 C07D417/14;C07D471/10 主分类号 C07D417/14
代理机构 代理人
主权项 1. A compound according to formula (I): or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein A is X is N or C—R7;R is hydrogen, R1, halogen, cyano, nitro, —OR1, —C(═O)—R1, —C(═O)O—R1, —C(═O)NR11—R1, —S(═O)2—R1, —NR11C(═O)—R1, —NR11C(═O)NR11R11, —NR11C(═O)O—R1, —NR11S(═O)2R1 or —NR11R11;R1 is C1-6 alkyl substituted with 0-4 R1a, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 R1a, C2-6 alkynyl substituted with 0-3 R1a, C3-10 cycloalkyl substituted with 0-3 R1a, C6-10 aryl substituted with 0-3 R1a, a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R1a, or a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R1a;R1a is hydrogen, ═O, F, Cl, Br, 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)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-2 Ra, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-3 Ra, or —(CH2)r-5-7 membered heterocycle or heteroaryl, each comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Ra;R2 is C6-10 aryl substituted with 0-4 R2a, a 5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 1-4 R2a, or a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R2a;R2a at each occurrence is independently selected from 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)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-2 Ra, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra, or —(CH2)r-5-7 membered heterocycle or heteroaryl, each comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra;R3 is C1-6 alkyl substituted with 0-3 R3a, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 R3a, C2-6 alkynyl substituted with 0-3 R3a, C3-10 cycloalkyl substituted with 0-3 R3a, C6-10 aryl substituted with 0-3 R3a, a 5-10 membered heterocyclyl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R3a or a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R3a;R3a is hydrogen, ═O, F, Cl, Br, 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)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-2 Ra, C1-6haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra, or —(CH2)r-5-7 membered heterocycle or heteroaryl, each comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-1 Ra;R4 and R5 are independently selected from hydrogen, C1-4 alkyl substituted with 0-1 Rf, (CH2)-phenyl substituted with 0-3 Rd, and a —(CH2)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;R6 and R7 are independently at each occurrence is selected from hydrogen, ═O, F, Cl, Br, 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)2Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-2 Ra, C1-6haloalkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-3 Ra, or —(CH2)r-5-7 membered heterocycle or heteroaryl, each comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Ra, provided R6 and R7 are not both hydrogen;R11 at each occurrence is independently hydrogen, Re, C1-4 alkyl substituted with 0-1 Rf, CH2-phenyl substituted with 0-3 Rd, or —(CH2)-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd; orR11 and along with another R11, R1, or R2 on the same nitrogen atom may join to form an optionally substituted heterocycle;Ra is 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, —(O)pNR11R11, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-1 Rf, C1-6 haloalkyl, —(CH2)r-3-14 membered carbocycle, or —(CH2)r-5-7 membered heterocycle or heteroaryl, each comprising carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p; or two Ra on adjacent or the same carbon atom form a cyclic acetal of the formula —O—(CH2)n—O—, or —O—CF2—O—, wherein n is selected from 1 or 2;Rb is hydrogen, Re, C1-6 alkyl substituted with 0-2 Rd, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or (CH2)r-phenyl substituted with 0-3 Rd;Rc is C1-6 alkyl substituted with 0-1 Rf, C3-6 cycloalkyl, or (CH2)r-phenyl substituted with 0-3 Rf;Rd is 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 is selected from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)r-phenyl substituted with 0-3 Rf;Rf is hydrogen, halo, NH2, OH, or O(C1-6alkyl);p is 0, 1, or 2;r is 0, 1, 2, 3, or 4; andm is 0, 1, or 2.
地址 Princeton NJ US