Benzisothiazoles useful for treating or preventing HCV infection
View Patent ↗The present invention relates to benzisothiazoles and pharmaceutical compositions thereof that inhibit replication and/or proliferation of HCV virus. The present invention also relates to the use of the benzisothiazoles and pharmaceutical compositions comprising the compounds to treat or prevent HCV infections.
1. A compound of Formula II,
or a pharmaceutically acceptable salt or S-oxide thereof, wherein,
each R 1 is independently selected from —H, halogen, mono- to trihalomethyl, —NO 2 , —N(R 3 )R 3 , —S(O) 0-2 R 3 , —SO 2 N(R 3 )R 3 , optionally substituted C 1-12 alkoxy, optionally substituted C 1-6 alkyl, and optionally substituted aryl C 0-6 alkyl
B is selected from absent, optionally substituted C 1-6 alkylene, —C═O, —C(═O)C(═O)—,
—S(O) 2 , —C(═O)N(R 4 )—, —C(═NR 5 )N(R 4 )—, —C(═S)N(R 4 )—, —C(═S)O—, and —C(═O)O—
R 2 is an optionally substituted aryl-aryl;
each R 3 is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted —C(═O)C 1-6 alkyl, optionally substituted aryl C 0-6 alkyl, optionally substituted heteroaryl C 0-6 alkyl and optionally substituted heterocyclyl C 0-6 alkyl; optionally two of R 3 , together with the nitrogen to which they are attached, combine to form an optionally substituted heterocyclyl containing one to three heteroatoms;
each R 4 is independently selected from —H and optionally substituted C 1-6 alkyl,
—S(O) 0-2 R 3 , —C(═O)N(R 3 )(R 3 ), optionally substituted aryl C 1-6 alkyl;
each R 5 is independently selected from —H, —CN, —NO 2 , —OR 3 , —S(O) 0-2 R 3 , —CO 2 R 3 , optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, and optionally substituted C 2-6 alkynyl;
M is C 2-4 alkylene, C 2-4 alkenylene, or C 2-4 alkynylene; and
each R 9 is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl C 0-6 alkyl and optionally substituted heterocyclyl C 0-6 alkyl; and optionally two of R 9 , together with the nitrogen to which they are attached, combine to form an optionally substituted heterocyclyl containing one to three heteroatoms.
2. The compound according to claim 1 , wherein R 1 is chloro, bromo, trifluoromethyl, methoxy, C 1-3 alkyl, —N(H)—C 1-3 alkyl, —SO 2- C 1-5 alkyl, —SO 2 NH 2 , —SO 2 N(H)C 1-5 alkyl, or phenyl optionally substituted with one or more methoxy, isopropoxy or fluoro.
3. A compound of Formula II,
or a pharmaceutically acceptable salt, or S-oxide thereof, wherein,
B is selected from optionally substituted C 1-6 alkyl, —C(═O)—, —S(O) 0-2 —, —C(═O)N(R 4 )— or is absent
each R 1 is independently selected from —H, halogen, mono- to trihalomethyl, —CN, —NO 2 , —OR 3 , —N(R 3 )R 3 , —S(O) 0-2 R 3 , —N(R 3 )C(═O)N(R 3 )R 3 , —SO 2 N(R 3 )R 3 , —CO 2 R 3 , —C(═O)N(R 3 )R 3 , —C(═NR 5 )N(R 3 )R 3 , —C(═NR 5 )R 3 , —N(R 3 )SO 2 R 3 , —N(R 3 )C(O)R 3 , —NC(═O)CH(R 3 )N(R 3 )R 3 , —NCO 2 R 3 , —C(═O)R 3 , optionally substituted C 1 -C 12 alkoxy, optionally substituted C 1-6 alkyl, optionally substituted aryl C 0-6 alkyl and optionally substituted heterocyclyl C 0-6 alkyl;
R 2 is an optionally substituted aryl-aryl;
each R 3 is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted —C(═O)C 1-6 alkyl, optionally substituted aryl C 0-6 alkyl, optionally substituted heteroaryl C 0-6 alkyl and optionally substituted heterocyclyl C 0-6 alkyl; optionally two of R 3 , together with the nitrogen to which they are attached, combine to form an optionally substituted heterocyclyl containing one to three heteroatoms;
each R 4 is independently selected from —H and optionally substituted C 1-6 alkyl,
—S(O) 0-2 R 3 , —C(═O)N(R 3 )(R 3 ), optionally substituted aryl C 1-6 alkyl;
each R 5 is independently selected from —H, —CN, —NO 2 , —OR 3 , —S(O) 0-2 R 3 , —CO 2 R 3 , optionally substituted C 1-6 alkyl, optionally substituted C 2-6 alkenyl, and optionally substituted C 2-6 alkynyl;
M is C 2-4 alkylene, C 2-4 alkenylene, or C 2-4 alkynylene; and
each R 9 is independently selected from —H, optionally substituted C 1-6 alkyl, optionally substituted aryl C 0-6 alkyl and optionally substituted heterocyclyl C 0-6 alkyl; and optionally two of R 9 , together with the nitrogen to which they are attached, combine to form an optionally substituted heterocyclyl containing one to three heteroatoms.
4. The compound according to claim 3 , wherein B is C 1-3 alkyl, —S(O) 2 — or —C(═O)N(H)—.
5. The compound according to claim 4 , wherein B is methylene.