| 摘要 |
The invention provides compounds that are useful in the treatment of hepatitis C virus (HCV) infections. The compounds have the formula (1):;
or a salt, N-oxide, tautomer or stereoisomer thereof, wherein A is CH or N; E is CH or N;
R1 is selected from:
an optionally substituted acyclic C1-8 hydrocarbon group wherein one carbon atom of the acyclic C1-8 hydrocarbon group may optionally be replaced by O, S, NRc, S(O) or SO2, or two adjacent carbon atoms of the acyclic C1-8 hydrocarbon group may optionally be replaced by CONRc, NRcCO, NRcSO2 or SO2NRc provided that in each case at least one carbon atom of the acyclic C1-8 hydrocarbon group remains; andan optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S;R2 is hydrogen or X—R8;X is a C1-8 alkanediyl group wherein one carbon atom of the C1-8 alkanediyl group may optionally be bonded to a —CH2—CH2— moiety to form a cyclopropane-1,1-diyl group or two adjacent carbon atoms of the C1-8 alkanediyl group may optionally be bonded to a —(CH2)n moiety, where n is 1 to 5, to form a C3-7-cycloalkane-1,2-diyl group;R3 is an optionally substituted 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0-3 heteroatom ring members selected from N, O and S;R4 is hydrogen or R4a wherein R4a is halogen; cyano; C1-4 alkyl; fluoro-1-4 alkyl; C1-4 alkoxy; fluoro-C1-4 alkoxy; hydroxy-C1-4 alkyl; or C1-2 alkoxy-C1-4 alkyl;R5 is hydrogen or R5a wherein R5a is selected from C1-2 alkyl optionally substituted with fluorine; C1-3 alkoxy optionally substituted with fluorine; halogen; cyclopropyl; and cyano;R8 is hydroxy or C(═O)NR10R11; provided that when R8 is hydroxy, there are at least two carbon atoms in line between the hydroxy group and the nitrogen atom to which X is attached;R10 is hydrogen or C1-4 alkyl; andR11 is hydrogen; amino-C2-4 alkyl or hydroxy-C2-4 alkyl;but excluding the compounds 1-(3-benzoylphenyl)-ethylamine and 1-(3-furan-2-oylcarbonylphenyl)-ethylamine. |
| 主权项 |
1. A compound of the formula (1):or a salt, N-oxide, tautomer or stereoisomer thereof, wherein:
A is CH; E is CH; R1 is selected from;
an acyclic C1-8 hydrocarbon group optionally substituted with one or two substituents R6, wherein one carbon atom of the acyclic C1-8 hydrocarbon group may optionally be replaced by a heteroatom or group selected from O, S, NRc, S(O) and SO2, or two adjacent carbon atoms of the acyclic C1-8 hydrocarbon group may optionally be replaced by a group selected from CONRc, NRcCO, NRcSO2 and SO2NRc provided that in each case at least one carbon atom of the acyclic C1-8 hydrocarbon group remains; anda monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S, the carbocyclic or heterocyclic group being optionally substituted with one or two substituents R7a; R2 is X—R8; X is a C1-8 alkanediyl group wherein one carbon atom of the C1-8 alkanediyl group may optionally be bonded to a —CH2—CH2— moiety to form a cyclopropane-1,1-diyl group or two adjacent carbon atoms of the C1-8 alkanediyl group may optionally be bonded to a —(CH2)n moiety, where n is 1 to 5, to form a C3-7-cycloalkane-1,2-diyl group; R3 is a 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0, 1, 2 or 3 heteroatom ring members selected from N, O and S, and being optionally substituted with one or more substituents R13; R4 is selected from hydrogen and a substituent R4a; R4a is selected from halogen; cyano; C1-4 alkyl optionally substituted with one or more fluorine atoms; C1-4 alkoxy optionally substituted with one or more fluorine atoms; hydroxy-C1-4 alkyl; and C1-2 alkoxy-C1-4 alkyl; R5 is selected from hydrogen and a substituent R5a; R5a is selected from C1-2 alkyl optionally substituted with one or more fluorine atoms; C1-3 alkoxy optionally substituted with one or more fluorine atoms; halogen; cyclopropyl; and cyano; R6 is selected from hydroxy; fluorine; carbamoyl; mono- or di-C1-4 alkylcarbamoyl; nitro; amino; mono- or di-C1-4 alkylamino; a monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1 or 2 are heteroatom ring members selected from O, N and S, the carbocyclic or heterocyclic group being optionally substituted with one or two substituents R7b; R7a and R7b are each independently selected from (═O); (═S); amino; halogen; cyano; hydroxy; C1-4 alkyl; hydroxy-C1-4 alkyl; amino-C1-4 alkyl; mono- and di-C1-4 alkylamino-C1-4 alkyl; R8 is selected from a hydroxy group and C(═O)NR10R11; provided that when R8 is hydroxy, there are at least two carbon atoms in line between the hydroxy group and the nitrogen atom to which X is attached; R10 is selected from hydrogen and C1-4 alkyl; R11 is selected from hydrogen; amino-C2-4 alkyl and hydroxy-C2-4 alkyl; R13 is selected from halogen; cyano; (═O); (═S); nitro; CH═NOH; and a group Ra-Rb; Ra is a bond, O, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; Rb is hydrogen; a cyclic group Rd; or an acyclic C1-8 hydrocarbon group optionally substituted with one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, carboxy, amino, mono- or di-C1-4 alkylamino, and a cyclic group Rd; wherein one or two but not all of the carbon atoms of the acyclic C1-8 hydrocarbon group may optionally be replaced by O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; SO2NRc or NRcSO2; the cyclic group Rd is a monocyclic carbocyclic or heterocyclic group having from 3 to 7 ring members, of which 0, 1, 2 or 3 are heteroatom ring members selected from O, N and S and oxidised forms thereof, the carbocyclic or heterocyclic group being optionally substituted with one or more substituents selected from R14; R14 is selected from oxo; halogen; cyano; and Ra—Re; Re is hydrogen or an acyclic C1-8 hydrocarbon group optionally substituted with one or more substituents selected from phenyl; hydroxy; oxo; halogen; cyano; carboxy; amino; mono- or di-C1-4 alkylamino; wherein one or two but not all of the carbon atoms of the acyclic C1-8 hydrocarbon group may optionally be replaced by O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; SO2NRc or NRcSO2; X1 is O or NRc; X2 is ═O or ═NRc; and Rc is hydrogen or C1-4 alkyl;but excluding the compounds 1-(3-benzoylphenyl)-ethylamine and 1-(3-furan-2-oylcarbonylphenyl)-ethylamine. |
