发明名称 ANTI-VIRAL COMPOUNDS
摘要 The present invention relates to anti-HCV compounds, compositions comprising the same and methods of using the same to treat HCV infection.
申请公布号 US2014364617(A1) 申请公布日期 2014.12.11
申请号 US201114368266 申请日期 2011.12.15
申请人 ABBVIE INC. 发明人 Krueger Allan C.;Kati Warren M.;Maring Clarence J.;Wagner Rolf;Hutchins Charles W.
分类号 C07D403/14;C07D409/14 主分类号 C07D403/14
代理机构 代理人
主权项 1. A compound of Formula (II) or pharmaceutically acceptable salts thereof: wherein: A is (a) absent; or (b) a cyclic group independently selected from aryl, heteroaryl, heterocyclic, C3-C8 cycloalkyl, and C3-C8 cycloalkenyl, each optionally substituted; wherein A, when present, is substituted with -L-E or -L3-D, wherein L, E, L3 and D are defined as below; Y is (a) absent; or (b) an optionally substituted aliphatic group selected from the group consisting of O, S, N(R11), C1-C8, alkyl, C2-C8, alkenyl, C2-C8, alkynyl, C3-C8, cycloalkyl, C3-C8 cycloalkenyl, and heterocyclic, each optionally substituted; or a combination thereof; wherein Y, when present, is substituted with -L-E or -L3-D, wherein L, E, L3 and D are defined as below; Z is (a) absent; or (b) an optionally substituted linear aliphatic group; optionally Z contains a group selected from O, N(R11), C(O), S(O)2, C(O)O, C(O)N(R11), OC(O)O, OC(O)N(R11), S(O)2N(R11), N(R11)C(O)N(R11), N(R11)C(O)C(O)N(R11), N(R11)S(O)2N(R11), C(O)N(R11)S(O)2 and C(O)N(R11)S(O)2N(R11); wherein Z, when present, is substituted with -L-E or -L3-D, wherein L, E, L3 and D are defined as below; wherein at least two of A, Y, and Z are optionally present; R11 at each occurrence is independently hydrogen or optionally substituted C1-C8 alkyl; R1 and R2 at each occurrence are each independently selected from the group consisting of hydrogen, halogen, cyano, optionally substituted C1-C4 alkyl, —O—R11, —NRaRb, —C(O)R11, —CO2R11, and —C(O)NRaRb; wherein at least one of R1 and R2 independently substituted with -L-E or -L3-D as defined below; Ra and Rb at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8, alkyl, and optionally substituted C2-C8, alkenyl; or Ra and Rb can be taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclic or optionally substituted heteroaryl group; Q and J are each independently selected from: R3 and R4 at each occurrence are each independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, and optionally substituted C3-C8 cycloalkyl; or alternatively, R3 and R4 can be taken together with the carbon atom to which they are attached to form optionally substituted C3-C8, cycloalkyl or optionally substituted heterocyclic; R5 at each occurrence is independently hydrogen, optionally substituted C1-C8, alkyl, or optionally substituted C3-C8 cycloalkyl; R6 at each occurrence is independently selected from the group consisting of —C(O)—R12, —C(O)—C(O)—R12, —S(O)2—R12, and —C(S)—R12; R12 at each occurrence is independently selected from the group consisting of: optionally substituted C1-C8 alkyl, —O—R11, —NRaRb, —R13, and —NRcRd; R13 at each occurrence is independently selected from the group consisting of hydrogen, C1-C8alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted; and Rc and Rd at each occurrence are each independently selected from the group consisting of hydrogen, —R3, —C(O)—R13, —C(O)—OR13, —S(O)2—R13, —C(O)N(R13)2, and —S(O)2N(R13)8; m is 0, 1, or 2; n is 1, 2, 3, or 4; X at each occurrence is independently selected from O, S, S(O), SO2, and C(R7)2 provided that when m is 0, X is C(R7)2; and R7 at each occurrence is independently selected from the group consisting of hydrogen, halogen, —C1-C4 alkyl, cyano, —O—R11, —NRaRb, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted —C1-C4 alkyl; or two vicinal R7 groups can be taken together with the two adjacent atoms to which they are attached to form a fused, optionally substituted C3-C8 cycloalkyl or optionally substituted heterocyclic ring; optionally substituted cyclopropyl; or alternatively two geminal R7 groups can be taken together with the carbon atom to which they are attached to form a spiro, optionally substituted C3-C8 cycloalkyl or optionally substituted heterocyclic ring, -L-E or -L3-D are as follows: E is (i) C3-C14 carbocycle or 3- to 14-membered heterocycle, and is optionally substituted with one or more RA; or (ii) E is -LS-RE; L is -LS-, -LS-O-LS′, -LS-C(O)-LS′-, -LS-S(O)2-LS′, -LS-S(O)-LS′-, -LS-OS(O)2-LS′-, -LS-S(O)2O-LS′-, -LS-OS(O)-LS′-, -LS-S(O)O-LS′-, -LS-C(O)O-LS′-, -LS-OC(O)-LS′-, -LS-OC(O)O-LS′-, -LS-C(O)N(RB)-LS′-, -LS-N(RB)C(O)-LS′-, -LS-C(O)N(RB)O-LS′-, -LS-N(RB)C(O)O-LS′-, -LS-OC(O)N(RB)-LS′-, -LS-C(O)N(R)N(RB)-LS′-, -LS-S-LS′-, -LS-C(S)-LS′-, -LS-C(S)O-LS′-, -LS-OC(S)-LS′-, -LS-C(S)N(RB)-LS′-, -LS-N(RB)-LS′-, -LS-N(RB)C(S)-LS′-, -LS-N(R)S(O)-LS′-, -LS-N(RB)S(O)2-LS′-, -LS-S(O)2N(RB)-LS′-, -LS-S(O)N(RB)-LS′-, -LS-C(S)N(RB)O-LS′-, -LS-C(O)N(RB)C(O)-LS′-, -LS-N(RB)C(O)N(RB′)-LS′-, -LS-N(RB)SO2N(RB′)-LS′-, -LS-N(R)S(O)N(RB′)-LS′-, or -LS-C(S)N(RB)N(RB′)-LS′-; LS and LS′ are each independently selected at each occurrence from bond; or C1-C6 alkylene, C2-C6 alkenylene or C2-C6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; RA is independently selected at each occurrence from halogen, oxo, thioxo, hydroxy, mercapto, nitro, cyano, amino, carboxy, formyl, phosphonoxy, or phosphono; or -LS-RE; RB and RB′ are each independently selected at each occurrence from hydrogen; or C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C3-C6 carbocycle or 3- to 6-membered heterocycle; or C3-C6 carbocycle or 3- to 6-membered heterocycle; wherein each C3-C6 carbocycle or 3- to 6-membered heterocycle in RB or RB′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6haloalkenyl or C2-C6 haloalkynyl; RE is independently selected at each occurrence from —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′), —N(RS)C(O)RS′, —N(RS)C(O)N(RS′RS″), —N(RS)SO2RS′, —SO2N(RSRS′), —N(RS)SO2N(RS′RS″), —N(RS)S(O)N(RS′RS″), —OS(O)—RS, —OS(O)2—RS, —S(O)2ORS, —S(O)ORS, —OC(O)ORS, —N(RS)C(O)ORS′, —OC(O)N(RSRS′), —N(RS)S(O)—RS′, —S(O)N(RSRS′) or —C(O)N(RS)C(O)—RS′; or C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl or C2-C6 haloalkynyl; RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′) or —N(RS)C(O)RS′; or C3-C6 carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl or C2-C6 haloalkynyl; RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6 alkyl, C2-C6alkenyl or C2-C6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RS, RS′ or RS′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl or C2-C6haloalkynyl; L3 is bond or -LS-K-LS′-, wherein K is selected from bond, —O—, —S—, —N(RB)—, —C(O)—, —S(O)2—, —S(O)—, —OS(O)—, —OS(O)2—, —S(O)2O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(RB)—, —N(RB)C(O)—, —N(RB)C(O)O—, —OC(O)N(RB)—, —N(RB)S(O)—, —N(RB)S(O)2—, —S(O)N(RB)—, —S(O)2N(RB)—, —C(O)N(RB)C(O)—, —N(RB)C(O)N(RB′)—, —N(RB)SO2N(RB′)—, or —N(RB)S(O)N(RB′)—; D is C3-C12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more RA; or D is C3-C12 carbocycle or 3- to 12-membered heterocycle which is substituted with J and optionally substituted with one or more RA, where J is C3-C12 carbocycle or 3- to 12-membered heterocycle and is optionally substituted with one or more RA, or J is —SF5; or D is hydrogen or RA; RA is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -LS-RE, wherein two adjacent RA, taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; RB and RB′ are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RB or RB′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; RE is independently selected at each occurrence from —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′), —N(RS)C(O)RS′, —N(RS)C(O)N(RS′R5″), —N(RS)SO2RS′, —SO2N(RSRS′), —N(RS)SO2N(RS′RS″), —N(RS)S(O)N(RS′RS″), —OS(O)—RS, —OS(O)2—RS, —S(O)2ORS, —S(O)ORS, —OC(O)ORS, —N(RS)C(O)ORS′, —OC(O)N(RSRS′), —N(RS)S(O)—RS′, —S(O)N(RSRS′), —P(O)(ORS)2, or —C(O)N(RS)C(O)—RS′; or C1-C6alkyl, C2-C6 alkenyl or C2-C6alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C3-C6 carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl, C(O)ORS, or —N(RSRS′); RL is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—RS, —S—RS, —C(O)RS, —OC(O)RS, —C(O)ORS, —N(RSRS′), —S(O)RS, —SO2RS, —C(O)N(RSRS′) or —N(RS)C(O)RS′; or C3-C6 carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6 haloalkenyl or C2-C6 haloalkynyl; wherein two adjacent RL, taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; LS and LS′ are each independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene, each of which is independently optionally substituted at each occurrence with one or more RL; and RS, RS′ and RS″ are each independently selected at each occurrence from hydrogen; C1-C6alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, —O—C1-C6 alkyl, —O—C1-C6 alkylene-O—C1-C6 alkyl, or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in RS, RS′ or RS′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C2-C6 haloalkenyl or C2-C6 haloalkynyl.
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