Claims for Patent: 9,006,387

Summary for Patent: 9,006,387

Title:	Anti-viral compounds
Abstract:	Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
Inventor(s):	Rolf Wagner, John K. Pratt, Dachun Liu, Michael D. Tufano, David A. Degoey, Warren M. Kati, Charles W. Hutchins, Pamela L. Donner, John T. Randolph, Christopher E. Motter, Lissa T. Nelson, Sachin V. Patel, Mark A. Matulenko, Ryan G. Keddy, Tammie K. Jinkerson, Todd W. Rockway, Clarence J. Maring, Douglas K. Hutchinson, Charles A. Flentge, David A. Betebenner, Kathy Sarris, Kevin R. Woller, Seble H. Wagaw, Jean C. Califano, Wenke Li, Daniel D. Caspi, Mary E. Bellizzi, Yi Gao, Allan C. Krueger
Assignee:	AbbVie Inc
Application Number:	US14/180,886
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,006,387
Patent Claims:	1. A method of treating HCV infection, comprising administering to an HCV patient a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein: X is wherein the nitrogen ring atom is directly linked to -L3-D, and wherein X is optionally substituted with one or more RA; L1, L2 and L3 are bond; A and B are each independently and are each independently optionally substituted with one or more RA; D is C3-C12carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more RA; Y is —N(RB)C(O)C(R1R2)N(R5)-T-RD or —N(RB)C(O)C(R3R4)C(R6R7)-T-RD; Z is —N(RB)C(O)C(R8R9)N(R12)-T-RD or —N(RB)C(O)C(R10R11)C(R13R14)-T-RD; R1 is RC, and R2 and R5, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; R3 and R6 are each independently RC, and R4 and R7, taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more RA; R8 is RC, and R9 and R12, taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more RA; R10 and R13 are each independently RC, and R11 and R14, taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more RA; T is each independently selected at each occurrence from bond, -LS-, -LS-M-LS′-, or -LS-M-LS′-M′-LS″-, wherein M and M′ are each independently selected at each occurrence 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′)—, —N(RB)S(O)N(RB′)—, C3-C12carbocycle or 3- to 12-membered heterocycle, and wherein said C3-C12carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more RA; RD is each independently selected at each occurrence from hydrogen or RA; RA is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -LS-RE; RB and RB′ are each independently selected at each occurrence from hydrogen; or C1-C6alkyl, C2-C6alkenyl 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, 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; RC is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C1-C6alkyl, C2-C6alkenyl 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, 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 RC 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′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-C6alkyl, C2-C6alkenyl 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-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-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl; 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-C6carbocycle 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-C6haloalkenyl or C2-C6haloalkynyl; LS, 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-C6alkenyl 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, 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-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6haloalkyl, C2-C6haloalkenyl or C2-C6haloalkynyl. 2. The method of claim 1, wherein: T is independently selected at each occurrence from —C(O)-LS′-M′-LS″- or —N(RB)C(O)-LS′-M′-LS″-; and LS′ is each independently C1-C6alkylene, and is independently optionally substituted at each occurrence with one or more RL. 3. The method of claim 1, wherein: Y is —N(RB)C(O)C(R1R2)N(R5)-T-RD; Z is —N(RB)C(O)C(R8R9)N(R12)-T-RD; T is independently selected at each occurrence from —C(O)-LS′-M′-LS″-; and D is C5-C6carbocycle, 5- to 6-membered heterocycle, or 6- to 10-membered bicycles, and is substituted with one or more RA. 4. The method of claim 3, wherein T is independently selected at each occurrence from —C(O)-LS′-N(RB)C(O)-LS″- or —C(O)-LS′-N(RB)C(O)O-LS″-; and R2 and R5, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA; and R9 and R12, taken together with the atoms to which they are attached, form which is optionally substituted with one or more RA. 5. The method of claim 1, wherein RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano; or C1-C6alkyl, C2-C6alkenyl 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. 6. The method of claim 5, wherein LS, LS′ and LS″ are each independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene. 7. The method of claim 4, wherein RA is independently selected at each occurrence from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano; or C1-C6alkyl, C2-C6alkenyl 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. 8. The method of claim 7, wherein LS, LS′ and LS″ are each independently selected at each occurrence from bond; or C1-C6alkylene, C2-C6alkenylene or C2-C6alkynylene. 9. A method of claim 1, wherein said compound is dimethyl (2S,2'S)-1,1′-((2S,2'S)-2,2′-(4,4′-((2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl)bis(4,1-phenylene))bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl)dicarbamate.