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US 2011/0300103 A1Published application
Heterocyclic antiviral compounds
AssigneeRoche Palo Alto LLC
InventorsJavier de Vicente Fidalgo, Jim Li, Ryan Craig Schoenfeld, Francisco Xavier Talamas, Joshua Paul Gergely Taygerly
Life of this patent
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Abstract
Method for treating an HCV infection and inhibiting HCV replication with a compound of formula I wherein R1, R2, R3, R4, X1, X2, X3 and X4 and as defined herein
Claims10
A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof, a therapeutically effective quantity of a compound according to according to formula I wherein:
- X1 is N and X2, X3 and X4 are CR5;
- R1 is (a) a heteroaryl radical selected from the group consisting of pyridinyl, 2-oxo-1,2-dihydro-pyridin-3-yl, 3-oxo-3,4-dihydro-pyrazin-2-yl, 3-oxo-2,3-dihydro-pyridazin-4-yl, 2-oxo-1,2-dihydro-pyrimidin-4-one-5-yl, 6-oxo-1,6-dihydro-[1,2,4]triazin-5-yl, 2-oxo-2(H)-pyridin-1-yl, 6-oxo-6H-pyridazin-1-yl, 6-oxo-6H-pyrimidin-1-yl and 2-oxo-2H-pyrazin-1-yl said heteroaryl being optionally substituted by halogen, C1-6 alkyl, C1-3 haloalkyl, C1-6 hydroxyalkyl, C1-3 alkoxy-C1-3 alkyl, C1-6 alkoxy, X6(CH2)1-6CO2H or (h) X6—(CH2)2-6NRgRh wherein X6 is O or NRg, or;
- (b) a heterocyclic radical selected from the group consisting of 2-oxo-tetrahydro-pyrimidin-1-yl, 2-oxo-imidazolidin-1-yl, 2-oxo-piperidin-1-yl, 2-oxo-pyrrolidin-1-yl, 2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl and 2,5-dioxo-imidazolidin-1-yl and 2,4-dioxo-tetrahydro-pyrimidin-1-yl;
- R2 is hydrogen, C1-6 alkoxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy or halogen;
- R3 is (a) aryl, (b) heteroaryl, (c) NRaRb, (d) halogen wherein said aryl or said heteroaryl are optionally independently substituted with one to three substitutents selected from the group consisting of hydroxy, C1-6 alkoxy, C1-6 alkyl, C1-6 hydroxyalkyl, halogen, (CH2)nNRcRd, cyano, C1-6 alkoxycarbonyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, (CH2)0-3CO2H, SO2NH2, C1-6 alkylsulfinyl and C1-6 alkylsulfonyl or (e) —X—[C(R6)2-6NReRf wherein X is O or NR7, R7 is hydrogen or C1-3 alkyl, R6 is independently in each occurrence hydrogen, C1-3 alkyl or two R6 residues on the same carbon are C2-5 alkylene or two R6 residues on different carbons are C1-4 alkylene;
- Ra and Rb along with the nitrogen to which they are attached are a cyclic amine independently substituted by one to three groups independently selected from C1-6 alkyl, halogen or (CH2)nNReRf;
- Rc and Rd are independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 acyl, SO2R8 wherein R8 is (a) C1-6 alkyl, (b) haloalkyl, (c) C3-7 cycloalkyl, (d) C3-7 cycloalkyl-C1-3 alkyl, (e) C1-6 alkoxy-C1-6 alkyl or (f) SO2[C(R9)2]0-6NRkRl, C1-3 alkylcarbamoyl or C1-3 dialkylcarbamoyl;
- Re and Rf, are independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 acyl, SO2R8 wherein R8 is (a) C1-6 alkyl, (b) C1-6 haloalkyl, (c) C3-7 cycloalkyl, (d) C3-7 cycloalkyl-C1-3 alkyl, (e) C1-6 alkoxy-C1-6 alkyl or (f) SO2[C(R9)2]0-6NRkRl;
- Ri and Rj are (i) independently hydrogen, C1-3 alkyl or (CH2)2-6NRgRh or (ii) together with the nitrogen to which they are attached are (CH2)2X5(CH2)2 wherein X5 is O or NRk and Rk is hydrogen, C1-3 alkyl, C1-3 acyl or C1-3 alkylsulfonyl;
- R4 is hydrogen, CF3, CH2CF3, C3-5 cycloalkyl, halogen, C1-6 alkoxy, C1-3 haloalkoxy, CHR4aR4b or CR4aR4bR4c wherein
- (i) R4a, R4b, and R4c are independently selected from C1-3 alkyl, CD3, C1-2 alkoxy, C1-2 fluoroalkyl, C1-3 hydroxyalkyl, cyano or hydroxy;
- or,
- (ii) when taken together, R4a and R4b together are C2-4 alkylene and R4c is hydrogen, C1-3 alkyl, C1-2 alkoxy, halogen, C1-3 hydroxyalkyl, cyano or C1-2 fluoroalkyl or R4a and R4b together with the carbon to which they are attached are 3-oxetanyl, or tetrahydrofuran-2-yl;
- R5 is independently in each occurrence hydrogen, halogen, C1-6 alkoxy, or C1-6 alkyl;
- R8, Rg and Rh are independently in each occurrence hydrogen or C1-3 alkyl;
- Rk and Rl are (i) independently in each occurrence hydrogen or C1-6 alkyl or (ii) together with the nitrogen to which they are attached Rk and Rl form a cyclic amine;
- n is independently in each occurrence zero, one, two or three;
- or,
- a pharmaceutically acceptable salt thereof.
16 more elements
Dependencies are inferred from the claim text.