Quinoline inhibitors of HCV polymerase

A compound 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 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, 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]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) 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, 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]0-6 NRkRl;
• 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.