Macrocyclic indole derivatives useful as hepatitis C virus inhibitors
View Patent ↗Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R 1 , R 2 , R 4 , R 5 , R 6 and R 7 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.
1. A compound of Formula (I)
or a stereochemically isomeric form, N-oxide, salt, hydrate, or solvate thereof, wherein:
R 1 is a bivalent chain selected from
each R 3 is independently selected from the group comprising hydrogen, C 1-4 -alkyl and C 3-5 cycloalkyl;
a is 3, 4, 5 or 6;
each b is independently 1 or 2;
c is 1 or 2;
macrocycle A has 14 to 18 member atoms;
each R 2 is independently hydrogen, halo or C 1-4 -alkoxy;
R 4 and R 5 are hydrogen or R 4 and R 5 together form a double bond or a methylene group to form a fused cyclopropyl;
R 6 is hydrogen or methyl; and
R 7 is a C 3-7 cycloalkyl optionally substituted with halo.
2. The compound of claim 1 wherein,
R 1 is selected from —N(R 3 )—(CH 2 ) 4 —N(R 3 )—,
and,
each R 3 is independently selected from hydrogen and methyl.
3. The compound of claim 1 wherein R 2 is positioned the benzene group in para with respect to the bond linking this benzene to the indole group.
4. The compound of claim 1 wherein R 2 is selected from fluoro and methoxy.
5. The compound of claim 1 wherein R 7 is selected from cyclohexyl and 2-fluorocyclohexyl.
6. The compound of claim 1 wherein R 4 and R 5 together form a double bond.
7. The compound of claim 1 having the stereochemical configuration as illustrated by formula (IA)
8. The compound of claim 1 , selected from the group consisting of:
9. A pharmaceutical composition comprising a carrier, and as active ingredient an anti-virally effective amount of the compound of claim 1 .
10. The pharmaceutical composition of claim 9 , further comprising at least one other anti-HCV compound.
11. The pharmaceutical composition of claim 9 , further comprising at least one anti HIV compound.
12. The compound of claim 1 , which is
or a stereochemically isomeric form, N-oxide, salt, hydrate, or solvate thereof.
13. A pharmaceutical composition comprising a carrier, and as active ingredient an anti-virally effective amount of the compound of claim 12 .
14. The pharmaceutical composition of claim 13 , further comprising at least one other anti-HCV compound.
15. The pharmaceutical composition of claim 13 , further comprising at least one HIV compound.
16. The compound of claim 12 , which is
or a salt thereof.
17. The compound of claim 16 , which is
18. The compound of claim 1 , wherein macrocycle A has 17 or 18 member atoms.