Antiviral indoles
View Patent ↗Compounds of the formula (I) wherein A, B, D, M, Ar, W, X, Y, Z and R 1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
Ar is a moiety containing at least one aromatic ring and possesses 5-, 6-, 9- or 10-ring atoms optionally containing 1, 2 or 3 heteroatoms independently selected from N, O and S, which ring is optionally substituted by groups Q 1 and Q 2 ;
Q 1 is halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, aryl, heteroaryl, CONR a R b , (CH 2 ) 0-3 NR a R b , O(CH 2 ) 1-3 NR a R b , O(CH 2 ) 0-3 CONR a R b , O(CH 2 ) 0-3 aryl, O(CH 2 ) 0-3 heteroaryl, O(CR e R f )aryl, O(CR e R f )heteroaryl or OCHR c R d ;
R a and R b are each independently selected from hydrogen, C 1-4 alkyl and C(O)C 1-4 alkyl;
or R a , R b and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R c and R d are each independently selected from hydrogen and C 1-4 alkoxy;
or R c and R d are linked by a heteroatom selected from N, O and S to form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
and wherein said C 1-4 alkyl, C 1-4 alkoxy and aryl groups are optionally substituted by halogen or hydroxy;
R e is hydrogen or C 1-6 alkyl;
R f is C 1-6 alkyl;
Q 2 is halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy, where said C 1-4 alkyl and C 1-4 alkoxy groups are optionally substituted by halogen or hydroxy;
or Q 1 and Q 2 may be linked by a bond or a heteroatom selected from N, O and S to form a ring of 4 to 7 atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
A is C 3-6 alkyl or C 2-6 alkenyl,
or A is a non-aromatic ring of 3 to 8 ring atoms where said ring may contain a double bond and/or may contain a O, S, SO, SO 2 or NH moiety,
or A is a non-aromatic bicyclic moiety of 4 to 8 ring atoms,
and A is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
D is N or CR g ;
R g is hydrogen, fluorine, chlorine, C 1-4 alkyl, C 2-4 alkenyl or C 1-4 alkoxy, where said C 1-4 alkyl, C 2-4 alkenyl and C 1-4 alkoxy groups are optionally substituted by hydroxy or fluorine;
W is a bond, C═O, O, S(O) 0-2 or —(CR 10 R 11 )—(CR 12 R 13 ) 0-1 —;
X is —CR 14a — or N; Y is a bond, C═O, O, —CR 14 R 15 — or NR 14 ; and Z is a bond, C═O, O, S(O) 0-2 or —(CR 10 R 11 )—(CR 12 R 13 ) 0-1 — or NR 10 ; and none, one or two of W, Y and Z are a bond;
or X is C═O, O, —CR 14b R 15b — or NR 14b ; and Y is hydrogen or absent and Z is hydrogen or a group Q 1 or Q 2
R 10 , R 11 , R 12 , R 13 , R 14 , R 14a , R 14b , R 15 and R 15b are each independently selected from hydrogen, hydroxy, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, C(O)C 1-6 alkyl, Het, (CH 2 ) 0-3 NR 16 R 17 , C(O)(CH 2 ) 0-3 NR 16 R 17 , NHC(O)(CH 2 ) 0-3 NR 16 R 17 , O(CH 2 ) 1-3 NR 16 R 17 , S(O) 0-2 (CH 2 ) 0-3 NR 16 R 17 and C(O)(CH 2 ) 0-3 OR 16 ;
or one of R 10 , R 14 , R 14a and R 14b is linked to R 22 or R 23 to form a ring of 4 to 10 atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
or, when X is —CR 14a — and Z is —CR 10 R 11 — or NR 10 , R 10 is joined to R 14a to form a —(CH 2 )— 1-4 group, optionally substituted by C 1-4 alkyl;
Het is a heteroaliphatic ring of 4 to 7 ring atoms, which ring may contain 1, 2 or 3 heteroatoms selected from N, O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl;
R 16 and R 17 are independently selected from hydrogen, C 1-6 alkyl and (CH 2 ) 0-4 NR 18 R 19 ;
or R 16 , R 17 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R 18 and R 19 are independently selected from hydrogen and C 1-6 alkyl;
or R 18 , R 19 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R 1 is hydrogen or C 1-6 alkyl;
B is —CR 20 R 21 —, —C(═O)—, —SO— or —SO 2 —;
R 20 and R 21 are independently selected from hydrogen and C 1-6 alkyl;
or R 20 and R 21 , together with the carbon atom to which they are joined, form a C 3-6 cycloalkyl group;
M is C 4-8 alkylene or C 4-8 alkenylene, optionally substituted by R 22 , where 1, 2 or 3 of the carbon atoms in the C 4-8 alkylene or C 4-8 alkenylene groups is optionally replaced by O, NR 23 , S, SO, SO 2 , piperidinyl, piperazinyl or pyrrolidinyl,
where each R 23 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, (CH 2 ) 0-3 C 3-6 cycloalkyl, (CH 2 ) 1-3 OH, C 1-6 alkoxy, C(O)C 1-6 alkyl, (CH 2 ) 0-3 aryl, (CH 2 ) 0-3 Het, (CH 2 ) 0-3 heteroaryl, (CH 2 ) 1-3 NR 16 R 17 , C(O)(CH 2 ) 1-3 NR 16 R 17 , S(O) 0-2 (CH 2 ) 1-3 NR 16 R 17 , C(O)(CH 2 ) 1-3 OR 16 , (CH 2 ) 1-3 (CH 2 ) 0-3 aryl,
or R 23 is linked to one of R 10 , R 14 , R 14a and R 14b to form a ring of 4 to 10 atoms as hereinbefore described;
or where 2 or 3 of the carbon atoms in the C 4-8 alkylene or C 4-8 alkenylene group are replaced by NR 23 , then the R 23 groups can be joined to form a —(CH 2 )— 1-3 group, optionally substituted by C 1-2 alkyl,
where R 22 is halo, C 1-4 alkyl, (CH 2 ) 0-3 C 3-8 cycloalkyl, (CH 2 ) 0-3 aryl, (CH 2 ) 0-3 heteroaryl, (CH 2 ) 0-3 Het, oxo or (CH 2 ) 0-3 NR 16 R 17 ,
or R 22 is linked to one of R 10 , R 14 , R 14a and R 14b to form a ring of 4 to 10 atoms as hereinbefore described.
2. The compound according to claim 1 , wherein said compound is of formula (Ia):
wherein X is —CR 14a — or N; Y is a bond, C═O, O, —CR 14 R 15 — or NR 14 ; and Z is a bond, C═O, O, S(O) 0-2 , —(CR 10 R 11 )—(CR 12 R 13 ) 0-1 — or NR 10 ; and none, one or two of W, Y and Z are a bond.
3. The compound according to claim 1 , wherein said compound is of formula (Iao):
or a pharmaceutically acceptable salt thereof, wherein
Z is a bond, C═O, O, S(O) 0-2 , —(CR 10 R 11 )—(R 12 R 13 ) 0-1 — or NR 10 ;
and none, one or two of W, Y and Z are a bond;
X is —CR 14a — or N;
R 10 , R 11 , R 12 , R 13 , R 14 , R 14a and R 15 are each independently selected from hydrogen, hydroxy, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, C(O)C 1-6 alkyl, Het, (CH 2 ) 0-3 NR 16 R 17 , C(O)(CH 2 ) 0-3 NR 16 R 17 , NHC(O)(CH 2 ) 0-3 NR 16 R 17 , O(CH 2 ) 1-3 NR 16 R 17 , S(O) 0-2 (CH 2 ) 0-3 R 16 R 17 and C(O)(CH 2 ) 0-3 OR 16 ;
or one of R 10 , R 14 and R 14a is linked to R 22 or R 23 to form a ring of 4 to 10 atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
Het is a heteroaliphatic ring of 4 to 7 ring atoms, which ring may contain 1, 2 or 3 heteroatoms selected from N, O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl;
R 16 and R 17 are independently selected from hydrogen, C 1-6 alkyl and (CH 2 ) 0-4 NR 18 R 19 ;
or R 16 , R 17 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R 18 and R 19 are independently selected from hydrogen and C 1-6 alkyl;
or R 18 , R 19 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
M is C 4-8 alkylene or C 4-8 alkenylene, optionally substituted by R 22 , where 1, 2 or 3 of the carbon atoms in the C 4-8 alkylene or C 4-8 alkenylene groups is optionally replaced by O, NR 23 , S, SO, SO 2 , piperidinyl, piperazinyl or pyrrolidinyl,
where R 23 is hydrogen or C 1-6 alkyl, or R 23 is linked to one of R 10 , R 14 and R 14a to form a ring of 4 to 10 atoms as hereinbefore described;
where R 22 is halo, C 1-4 alkyl, (CH 2 ) 0-3 C 3-8 cycloalkyl, (CH 2 ) 0-3 aryl, (CH 2 ) 0-3 heteroaryl, (CH 2 ) 0-3 Het or oxo,
or R 22 is linked to one of R 10 , R 14 and R 14a to form a ring of 4 to 10 atoms as hereinbefore described.
4. The compound according to claim 2 in which Z is a bond, O, —CH 2 — or —CH 2 CH 2 —.
5. The compound according to claim 2 in which Y is selected from —CH 2 — and a bond.
6. The compound according to claim 2 in which X is —CH—.
7. The compound according to claim 1 , wherein the compound is of formula (Ib):
or a pharmaceutically acceptable salt therof, wherein X is C═O, O, —CR 14b R 15b — or NR 14b .
8. The compound according to claim 1 , wherein the compound is of formula (Ibo):
or a pharmaceutically acceptable thereof, wherein
Ar is a moiety containing at least one aromatic ring and possesses 5-, 6-, 9- or 10-ring atoms optionally containing 1, 2 or 3 heteroatoms independently selected from N, O and S, which ring is optionally substituted by groups Q 1 and Q 2 ;
Q 1 is halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, aryl, heteroaryl, CONR a R b , (CH 2 ) 0-3 NR a R b , O(CH 2 ) 1-3 NR a R b , O(CH 2 ) 0-3 CONR a R b , O(CH 2 ) 0-3 aryl, O(CH 2 ) 0-3 heteroaryl, O(CR e R f )aryl, O(CR e R f )heteroaryl or OCHR c R d ;
R a and R b are each independently selected from hydrogen, C 1-4 alkyl and C(O)C 1-4 alkyl;
or R a , R b and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R c and R d are each independently selected from hydrogen and C 1-4 alkoxy;
or R c and R d are linked by a heteroatom selected from N, O and S to form a heteroaliphatic ring of 4 to 7 ring atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
and wherein said C 1-4 alkyl, C 1-4 alkoxy and aryl groups are optionally substituted by halogen or hydroxy;
R e is hydrogen or C 1-6 alkyl;
R f is C 1-6 alkyl;
Q 2 is halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy, where said C 1-4 alkyl and C 1-4 alkoxy groups are optionally substituted by halogen or hydroxy;
or Q 1 and Q 2 may be linked by a bond or a heteroatom selected from N, O and S to form a ring of 4 to 7 atoms, where said ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
A is C 3-6 alkyl or C 2-6 alkenyl,
or A is a non-aromatic ring of 3 to 8 ring atoms where said ring may contain a double bond and/or may contain a O, S, SO, SO 2 or NH moiety,
or A is a non-aromatic bicyclic moiety of 4 to 8 ring atoms,
and A is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
D is N or CR g ;
R g is hydrogen, fluorine, chlorine, C 1-4 alkyl, C 2-4 alkenyl or C 1-4 alkoxy, where said C 1-4 alkyl, C 2-4 alkenyl and C 1-4 alkoxy groups are optionally substituted by hydroxy or fluorine;
W is a bond, C═O, O, S(O) 0-2 or —(CR 10 R 11 )—(CR 12 R 13 ) 0-1 —;
X is C═O, O, —CR 14 R 15 — or NR 14 ;
R 10 , R 11 , R 12 , R 13 , R 14 and R 15 are each independently selected from hydrogen, hydroxy, C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkoxy, C(O)C 1-6 alkyl, (CH 2 ) 0-3 aryl, (CH 2 ) 0-3 heteroaryl, (CH 2 ) 0-3 Het, (CH 2 ) 0-3 NR 16 R 17 , C(O)(CH 2 ) 0-3 NR 16 R 17 , NHC(O)(CH 2 ) 0-3 NR 16 R 17 , O(CH 2 ) 1-3 NR 16 R 17 , S(O) 0-2 (CH 2 ) 0-3 R 16 R 17 and C(O)(CH 2 ) 0-2 OR 16 ;
or R 14 is linked to R 22 or R 23 to form a ring of 4 to 10 atoms, where said ring is optionally substituted by halogen, hydrogen, C 1-4 alkyl or C 1-4 alkoxy;
Het is a heteroaliphatic ring of 4 to 7 ring atoms, which ring may contain 1, 2 or 3 heteroatoms selected from N, O or S or a group 5(O), S(O) 2 , NH or NC 1-4 alkyl;
R 16 and R 17 are independently selected from hydrogen, C 1-6 alkyl and (CH 2 ) 0-4 NR 18 R 19 ;
or R 16 , R 17 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R 18 and R 19 are independently selected from hydrogen and C 1-6 alkyl; or R 18 , R 19 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring may optionally contain 1 or 2 more heteroatoms selected from O or S or a group S(O), S(O) 2 , NH or NC 1-4 alkyl, and which ring is optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy;
R 1 is hydrogen or C 1-6 alkyl;
B is CR 20 R 21 —, —C(═O)—, —SO— or —SO 2 —;
R 20 and R 21 are independently selected from hydrogen and C 1-6 alkyl;
or R 20 and R 21 , together with the carbon atom to which they are joined, form a C 3-6 cycloalkyl group;
M is C 4-8 alkylene or C 4-8 alkenylene, optionally substituted by R 22a , where 1, 2 or 3 of the carbon atoms in the C 4-8 alkylene or C 4-8 alkenylene groups is optionally replaced by O, NR 23a , S, SO, SO 2 , aryl, heteroaryl or Het,
where R 23a is hydrogen or C 1-6 alkyl,
or R 23a is linked to R 14 to form a ring of 4 to 10 atoms as hereinbefore described;
where R 22a is halo, C 1-4 alkyl, (CH 2 ) 0-3 C 3-8 cycloalkyl, (CH 2 ) 0-3 aryl, heteroaryl, Het or oxo,
or R 22a is linked to R 14 to form a ring of 4 to 10 atoms as hereinbefore described.
9. The compound according to claim 7 in which X is C═O or —CH 2 —.
10. The compound according to claim 1 in which Ar is phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-furanyl or 3-furanyl, optionally substituted by groups Q 1 and Q 2 .
11. The compound according to claim 1 in which A is cyclopentyl or cyclohexyl, optionally substituted by halogen, hydroxy, C 1-4 alkyl or C 1-4 alkoxy.
12. The compound according to claim 1 in which D is CR g where R g is hydrogen or C 1-4 alkyl.
13. The compound according to claim 1 in which W is —CH 2 — or —CH 2 CH 2 —.
14. The compound according to claim 1 in which R 1 is hydrogen or methyl.
15. The compound according to claim 1 in which B is —SO 2 —.
16. The compound according to claim 1 in which M is C 5-8 alkylene, optionally substituted by C 1-4 alkyl or oxo, where 1 or 2 of the carbon atoms in the C 5-8 alkylene group is replaced by O, NH or N(C 1-4 alkyl).
17. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
(7R)-14-cyclohexyl-25-methyl-7,8-dihydro-6H-7,11-(epiminoethanoiminobutanothioiminomethano)indolo[1,2-e][1,5]benzoxazocine-15 ,21-dione 17,17-dioxide;
(7R)-14-cyclohexyl-24-methyl-7,8-dihydro-6H-7,11-(epiminoethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
(7R)-14-cyclohexyl-21,24-dimethyl-7,8-dihydro-6H-7,11-(epiminoethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
(7R)-14-[(1R,2S) or (1S,2R)-2-fluoro cyclohexyl]-21,24-dimethyl-7,8-dihydro-6H-7,11-(epiminoethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
7 (R,S)-14-cyclohexyl-22-methyl-7,8-dihydro-6H-7,11-(ethanoiminobutanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
(7R)-14-cyclohexyl-20,24-dimethyl-7,8-dihydro-6H-7,11-(epiminopropanoiminoethanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
13-cyclohexyl-19,22-dimethyl-6,7-dihydro-10,6-(methanoiminothioethanoiminoethanoiminomethano)indolo[1,2-d][1,4]benzoxazepin-14-one 16,16-dioxide;
(7R)-14-cyclohexyl-22,25-dimethyl-7,8-dihydro-6H-7,11-(epiminoethanoiminobutanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
(7S)-14-cyclohexyl-21-methyl-7,8-dihydro-6H-7,11-(epoxyethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
13-cyclohexyl-5,20,23-trimethyl-6,7-dihydro-5H-10,6-(methanoiminothiopropanoiminoethanoiminomethano)indolo[1,2-d][1,4]benzodiazepin-14-one 16,16-dioxide;
13-cyclohexyl-20,23-dimethyl-6,7-dihydro-5H-6,10-(epiminoethanoiminopropanothioiminomethano)indolo[2,1-a][2]benzazepin-14-one 16,16-dioxide;
8-cyclohexyl-19,22-dimethyl-1,12b-dihydro-5,1a -(methanoiminothiopropanoiminoethanoiminomethano)cyclopropa[c]indolo[2,1-a][2]benzazepin-13-one 15,15-dioxide;
13-cyclohexyl-20,23-dimethyl-6,7-dihydro-5H-10,6-(methanoiminothiopropanoiminoethanoiminomethano)indolo[2,1-a][2]benzazepin -14-one 16,16-dioxide;
16-cyclohexyl-3,6-dimethyl-17-phenyl-4,5,6,7,8,9-hexahydro-1H -13,15-(ethanediylidene)pyrrolo[2,1-f ][1,2,7,10,13]thiatetraazacyclohexadecine-2,12(3H)-dione 10,10-dioxide;
16-cyclohexyl-17-(4-methoxyphenyl)-3,6-dimethyl-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f ][1,2,7,10,13]thiatetra-azacyclohexadecin-12-one 10,10-dioxide;
16-cyclohexyl-3,6-dimethyl-17-(2-thienyl)-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f ][1,2,7,10,13]thiatetraazacyclohexadecin-12-one 10,10-dioxide;
(7R)-14-cyclohexyl-3-fluoro-21,24-dimethyl-7,8-dihydro-6H-7,11-(epiminoethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
(7R)-14-cyclohexyl-2-fluoro-21,24-dimethyl-7,8-dihydro-6H-7,11-(epiminoethanoiminopropanothioiminomethano)indolo[1,2-e][1,5]benzoxazocin-15-one 17,17-dioxide;
16-cyclohexyl-3,6-dimethyl-17-phenyl-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f][1,2,7,10,13]thiatetraazacyclo hexadecin-12-one 10,10-dioxide;
17-chloro-16-cyclohexyl-3,6-dimethyl-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f][1,2,7,10,13]thiatetraazacyclo hexadecin-12-one 10,10-dioxide;
16-cyclohexyl-17-(3-furyl)-3,6-dimethyl-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f][1,2,7,10,13]thiatetraazacyclo hexadecin-12-one 10,10-dioxide;
16-cyclohexyl-17-(2-methoxyphenyl)-3,6-dimethyl-2,3,4,5,6,7,8,9-octahydro-1H-13,15-(ethanediylidene)pyrrolo[2,1-f][1,2,7,10,13]thiatetraazacyclohexadecin-12-one 10,10-dioxide;
17-cyclohexyl-3,6-dimethyl-18-phenyl-3,4,5,6,7,8,9,10-octahydro-14,16-(ethanediylidene)pyrrolo[2,1-f][1,2,7,10,13]thiatetraazacycloheptadecine-2,13-dione 11,11-dioxide;
and pharmaceutically acceptable salts thereof.
18. A pharmaceutical composition which comprises an effective amount of a compound of the formula (I) according to claim 1 together with a pharmaceutically acceptable carrier.
19. A method of treating hepatitis C virus in a human or animal subject in need thereof, said method comprising administering to a human or animal subject a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.