Hepatitis C virus inhibitor and uses thereof
Disclosed is a compound of formula (I-a) as an inhibitor of hepatitis C virus (HCV), or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, usable to treat HCV infections or hepatitis C diseases and also usable as an inhibitor of HCV non-structural protein 5A (NS5A) In the formula (I-a), A and A′ are independently each R 1 , R 4 and R 6 are independently selected from the group consisting of fluorine, chlorine, bromine and iodine; R 2 and R 2 ′ are independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 3 and R 3 ′ are independently selected from substituted or unsubstituted C 1 -C 6 alkyl; R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine; n is 2, 3, 4 or 5; m is 0, 1, 2 or 3; and p is 0, 1, 2 or 3.
1. A compound of formula (I-a)
wherein A and A′ are independently
where R 2a and R 2b are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine; or R 2a and R 2b are cyclized to form a C 3 -C 8 cycloalkyl;
each R 1 is selected from the group consisting of fluorine, chlorine, bromine and iodine;
each R 4 is selected from the group consisting of fluorine, chlorine, bromine and iodine;
each R 6 is selected from the group consisting of fluorine, chlorine, bromine and iodine;
R 2 and R 2 ′ are independently selected from substituted or unsubstituted C 1 -C 6 alkyl; where substitution is performed by one or more substituents selected from the group consisting of halogen, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, nitro, hydroxyl, amino and cyano group;
R 3 and R 3 ′ are independently selected from substituted or unsubstituted C 1 -C 6 alkyl, where substitution is performed by one or more substituents selected from the group consisting of halogen, C 1 -C 3 alkyl C 1 -C 3 haloalkyl, nitro, hydroxyl, amino and cyano group; and
R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine and iodine;
n is 2, 3, 4 or 5;
m is 0, 1, 2 or 3; and
p is 0, 1, 2 or 3.
2. The compound of claim 1 , wherein the compound is selected from the group consisting of
3. A pharmaceutical composition comprising the compound of claim 1 or an optical isomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, and a pharmaceutically acceptable auxiliary, diluent or carrier.
4. The pharmaceutical composition of claim 3 , further comprising at least one HCV inhibitor for inhibiting HCV replication process and/or function of HCV protein.
5. The pharmaceutical composition of claim 4 , wherein the HCV replication process comprises HCV entry, HCV uncoating, HCV transcription, HCV replication, HCV assembly and/or HCV release.
6. The pharmaceutical composition of claim 4 , wherein the HCV protein is selected from the group consisting of NS2, NS3, NS4A, NS4B, NS5A and NS5B.
7. A method of preparing the compound of claim 1 , comprising:
(a) reacting compound 1 with diphenylmethanimine in an inert solvent to form compound 2
(b) reacting compound 2 with an acid in an inert solvent to form compound 3
(c) reacting compound 3 with
in an inert solvent to form compound 4
(d) reacting compound 4 with an acid in an inert solvent to form compound 5
(e) reacting compound 5 with
in an inert solvent to form the compound of formula (I)
and
(f) subjecting the compound of formula (I) to chiral resolution to form the compound of formula (I-a);
wherein, A, A′, R 1 , n, R 2 , R 2 ′, R 3 , R 3 ′, R 4 , m, R 5 , R 6 and p are defined in the same manner as in claim 1 .