Compounds of the formula I: including any possible stereoisomers thereof, or a pharmaceutically acceptable salt and/or solvate thereof, as well as pharmaceutical formulations and the use of compounds of formula I as HCV inhibitors.
1. A compound of formula I:
including any possible stereoisomers thereof, wherein:
R and R 1 , independently from one another, are benzoyl optionally substituted with one, two or three substituents each independently selected from halo and C 1 -C 6 alkyl, or —C(═O)-Het wherein Het is optionally substituted with one or two substituents independently selected from C 1-4 alkyl, or a group of formula —C(═O)—CH(R x )—R 6 , benzyloxycarbonyl, C 1 -C 6 alkyloxycarbonyl, a group of formula H 2 N—CH(R 7 )—C(═O)—, a group of formula R 8 —O—C(═O)—HN—CH(R 7 )—C(═O)—, or —C(═O)—C(═O)-phenyl;
R 6 is C 1 -C 4 alkyl, C 3-6 cycloalkyl, benzyl or phenyl wherein the phenyl may be optionally substituted with one, two or three substituents each independently selected from halo, C 1 -C 6 alkyl, methoxy, trifluoromethoxy or two substituents on adjacent ring atoms, together with the phenyl ring, form a benzodioxole, and, wherein the C 1 -C 4 alkyl is optionally substituted with mono- or diC 1 -C 4 alkylamino, phenylsulphonyl, Het, and, wherein benzyl is optionally substituted with one, two or three substituents each independently selected from halo, methoxy;
R x is selected from hydrogen, hydroxy, C 1 -C 6 alkoxy, amino, mono- or diC 1 -C 6 alkylamino, pyrrolidinyl, piperidinyl, morpholinyl, imidazolyl, C 1 -C 6 alkylcarbonylamino or C 1 -C 6 alkyloxycarbonylamino;
Het is a heterocyclic group comprising one or two heteroatoms selected from O and N and having 4 to 7 ring atoms wherein said heterocyclic ring is connected to the carbonyl carbon by a ring carbon atom and wherein at least one of said heteroatoms is adjacent to said ring carbon atom,
R 2 and R 3 , independently from one another, are hydrogen, hydroxyl, C 1 -C 4 alkyl or halo;
R 4 and R 5 , independently from one another, are hydrogen, C 1 -C 4 alkyl, halo or methoxy;
each R 7 independently is hydrogen, phenyl, or C 1 -C 4 alkyl optionally substituted with methoxy or phenyl; and,
R 8 is C 1 -C 4 alkyl or benzyl; or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 2 and R 3 are hydrogen, hydroxy or fluoro, in particular wherein R 2 and R 3 are hydrogen.
3. The compound of claim 1 , wherein R and R 1 , independently from one another, are a group of formula —C(═O)—CH(R x )—R 6 or —C(═O)-Het, in particular wherein R and R 1 , independently from one another, are groups of formula —C(═O)—CH(R x )—R 6 .
4. The compound of claim 1 , wherein R x is hydroxy, C 1 -C 6 alkoxy, amino, mono- or diC 1 -C 6 alkylamino, pyrrolidinyl, piperidinyl, morpholinyl, C 1 -C 6 alkylcarbonylamino or C 1 -C 6 alkyloxycarbonylamino; or wherein R x is hydroxyl, amino, diC 1 -C 4 alkylamino, or morpholinyl; or wherein R x is hydroxy, amino or dimethylamino.
5. The compound of claim 1 , wherein R 6 is a phenyl ring optionally substituted with one halo or C 1 -C 6 alkyl.
6. The compound of claim 1 , wherein R 6 is selected from phenyl and isopropyl.
7. The compound of claim 1 , wherein Het is selected from 2-pyridinyl, 2-pyrimidyl, 2-pyrazinyl, 2-imidazoyl, 2-thiazolyl, 2-thiophenyl, 2-pyrazolinyl, 2-piperidinyl, 2-pyrrolidinyl, 2-pyrrolyl, 2-furanyl, 2-tetrahydrofuranyl, 2-oxetanyl, 2- or 3-morpholinyl, and 2-piperazinyl, in particular 2-tetrahydrofuranyl.
8. The compound of claim 1 , wherein R 4 and R 5 are independently hydrogen, methyl, methoxy or chloro, in particular wherein R 4 and R 5 are hydrogen.
9. The compound of claim 1 , wherein the group
is substituted in meta position relative to the oxygen bridge between the two phenyl groups.
10. A method for inhibiting hepatitis C virus (HCV) replication, comprising contacting a compound according to claim 1 with an HCV.