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 method for inhibiting HCV replication, comprising administering to a subject in need thereof 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 method of claim 1 , wherein the,
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 method 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 method of claim 1 wherein R 2 is selected from fluoro and methoxy.
5. The method of claim 1 wherein R 7 is selected from cyclohexyl and 2-fluorocyclohexyl.
6. The method of claim 1 wherein R 4 and R 5 together form a double bond.
7. The method of claim 1 wherein the compounds of formula (I) have the stereochemical configuration as illustrated by formula (IA)
8. The method of claim 1 , wherein said compound has one of the structural formula II-1, II-2, II-3, III-1, III-2, III-3, III-4, IV-1, IV-2 or IV-3
9. The method of claim 1 , wherein macrocycle A has 17 or 18 member atoms.
10. The method of claim 1 , wherein the compound is
or a salt thereof.
11. The method of claim 10 , wherein the compound is
12. The method of claim 1 , comprising administering to said subject at least one other anti-HCV compound.
13. The method of claim 10 , comprising administering to said subject at least one other anti-HCV compound.