Methods for treating hepatitis C
View Patent ↗The present invention provides compounds, pharmaceutical compositions, and methods of using such compounds or compositions for treating infection by a virus, or for affecting viral IRES activity.
1. A compound of formula I
wherein:
X is:
a cyano group;
Y is:
a C 6 aryl, substituted with one or more of the following:
an alkoxy, optionally substituted with:
an alkoxy,
a hydroxy,
one or more halogen(s),
a 5 or 6 membered heterocycle, optionally substituted with:
a C 1 to C 6 alkyl, or
a hydroxy,
an amino group optionally substituted with one or more C 1 to C 6 alkyl(s),
a —NR i SO 2 R x group, where R x is a C 1 to C 6 alkyl and R i is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR j COR k group, where R k is:
a C 1 to C 6 alkyl,
a hydrogen, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), and R j is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —N═N + ═N − group, or
a —COR 1 , where R 1 is a 5 or 6 membered heterocycle optionally substituted with a hydroxy,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s),
a C 1 to C 6 alkyl group, optionally substituted with:
a —NHSO 2 R x group, where R x is as defined above, or
a —NR x SO 2 R x group, where R x is as defined above,
a haloalkoxy,
a halogen,
a hydroxy,
a —COOR x group, where R x is as defined above,
a —COR m group, where R m is:
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), where the one or more C 1 to C 6 alkyl(s) is optionally substituted with:
a hydroxy
a 5 or 6 membered heterocycle,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), or
an alkoxy,
a 3 to 7 membered heterocycle, optionally substituted with a C 1 to C 6 alkyl, optionally substituted with a dialkyl-amino, or
a —NHR n group, where R n is:
a —CH 2 CONH 2 , or
a C 6 to C 8 aryl optionally substituted with:
an alkyl,
one or more halogen(s),
a nitro group, or
one or more alkoxy(s),
a —NR o COR p group, where R p is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
an alkoxy, or
a C 6 to C 8 aryl,
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with a halogen,
a 5 or 6 membered heteroaryl optionally substituted with one or more C 1 to C 6 alkyl(s),
a hydrogen,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl,
a cyclopropylmethyl,
and where R o is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR q CONR q R r group, where R q is:
a hydrogen,
a C 1 to C 6 alkyl,
a haloalkyl,
a haloalkoxy, or
a —COR x group, where R x is as defined above, and where R r is:
a C 6 to C 8 aryl optionally substituted with:
a C 1 to C 6 alkyl,
a haloalkyl,
a —OR s group, where R s is a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a C 1 to C 6 alkyl optionally substituted with one or more of the following:
a halogen,
an alkenyl,
a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a —COOR x group, where R x is as defined above,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl,
a —NR t COOR u group, where R u is:
a C 1 to C 12 alkyl, optionally substituted with:
a C 6 to C 8 aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy,
an alkenyl,
an alkoxy,
an alkynyl,
a halogen, or
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with:
an alkoxy,
a halogen, or
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl.,
a cyclohexyl,
a cyclopropylmethyl,
a cyclopropylethyl,
a cyclobutylmethyl,
a (1-methylcyclopropyl)methyl, or
a 1-methylcyclopentyl,
and where R t is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR v SO 2 R w group, where R v is:
a hydrogen,
a —COR x , where R x is as defined above, or
a C 1 to C 6 alkyl, optionally substituted with:
a halogen,
a —COR x group, where R x is as defined above,
a —OCOR x group, where R x is as defined above,
a hydroxy, or
an alkoxy,
and where R w is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
a haloalkyl,
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle,
a C 2 to C 6 alkenyl,
a mono-alkyl-amino or dialkyl-amino optionally substituted on alkyl with a halogen,
a 5 or 6 membered heterocycle,
a 5 or 6 membered heteroaryl optionally substituted with:
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle, or
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl,
optionally substituted with a C 1 to C 6 alkyl, where R y is a C 1 to C 6 alkyl or hydrogen,
where R z is hydrogen or a C 1 to C 6 alkyl, optionally substituted with a C 6 to C 8 aryl,
a —SR x group, where R x is as defined above,
a —SO 2 R aa group, where R aa is:
a C 1 to C 6 alkyl,
an amino group,
a mono-alkyl-amino or dialkyl-amino group optionally substituted on alkyl with a hydroxy or a —COOR x group, where R x is as defined above,
a 5 or 6 membered heteroaryl,
a C 6 to C 8 aryl, or
a —NHR bb group, where R bb is:
a —C(═S)NH 2 group, or
a —PO(OR x ) 2 group, where R x is as defined above;
Z is:
a C 1 to C 6 alkyl optionally substituted with:
an alkoxy,
one or more halogen(s), or
a C 6 to C 8 aryl;
a C 2 to C 6 alkenyl;
a cyclopropyl;
a cyclobutyl;
a cyclopentyl;
a cyclohexyl;
a cyclopropylmethyl;
a cyclobutylmethyl; or
a cyclopentylmethyl;
R is a hydrogen, a halogen or an alkoxy;
R 1 is:
a hydrogen;
a hydroxy;
a halogen;
a haloalkyl;
a nitro group;
a 5 or 6 membered heteroaryl;
a 5 or 6 membered heterocycle;
an alkoxy optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle;
a C 6 to C 8 aryl optionally substituted with an alkoxy;
a —COR x group, where R x is as defined above; or
a C 1 to C 6 alkyl optionally substituted with a dialkyl-amino or a 5 or 6 membered heterocycle;
R 2 is:
a nitro group;
a hydrogen;
a halogen;
a hydroxy group;
a C 1 to C 6 alkyl group, optionally substituted with one or more halogen(s);
an amino group;
an alkoxy group optionally substituted with:
one or more halogen(s),
an —OCOR x group, where R x is as defined above,
an amino substituted with:
(i) —a cyclopropyl,
(ii) —a cyclobutyl,
(iii) —a cyclopentyl,
(iv) —a cyclohexyl, or
(v) —a cyclopropylmethyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl,
a 5 or 6 membered heteroaryl group, or
a C 6 to C 8 aryl group;
a —COOR x group, where R x is as defined above;
a haloalkyl;
an amide group optionally substituted with:
a hydroxy group, or
a C 6 to C 8 aryl;
a 5 or 6 membered heteroaryl;
a —OCOR x group, where R x is as defined above;
a —NHCOR jj group, where R jj is:
an alkoxy, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s);
a —OR kk group, where R kk is a 5 to 6 membered heteroaryl;
a —NHSO 2 R x group, where R x is as defined above;
a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; or
a cyclopropoxy; and
R 3 is:
a hydrogen; or
—CH 2 OCOR x , and R x is as defined above;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein:
Y is a C 6 aryl, substituted with one or more of the following:
an amino optionally substituted with one or more C 1 to C 6 alkyl(s),
a C 1 to C 6 alkyl group, optionally substituted with a —NHSO 2 R x group,
a —NR o COR p group, where R p is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen, or
a C 6 to C 8 aryl,
a 5 or 6 membered heterocycle,
a cyclopropyl, or
a cyclobutyl, and where R o is a hydrogen,
a —NR q CONR q R r group, where R q is:
a hydrogen, or
a C 1 to C 6 alkyl, and where R r is:
(a) a C 1 to C 6 alkyl optionally substituted with one or more of the following:
a halogen,
an alkenyl, or
a C 6 to C 8 aryl,
(b) —a cyclopropyl, —a cyclobutyl, or —a cyclopentyl;
a —NR t COOR u group, where R u is:
a C 1 to C 12 alkyl, optionally substituted with:
a C 6 to C 8 aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy,
an alkenyl,
an alkoxy,
an alkynyl,
a halogen, or
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with an alkoxy,
a 5 or 6 membered heterocycle,
a cyclobutyl,
a cyclopentyl,
a cyclopropylmethyl,
a cyclopropylethyl,
a cyclobutylmethyl,
a (1-methylcyclopropyl)methyl, or
a 1-methylcyclopentyl, and where R t is:
a hydrogen, or
a C 1 to C 6 alkyl,
a —NR v SO 2 R w group, where R v is a hydrogen, and where R w is:
(i) a C 1 to C 6 alkyl optionally substituted with a halogen; or
(ii) a cyclopropyl;
where R z is a C 1 to C 6 alkyl, or
a —NHR bb group, where R bb is a —PO(OR x ) 2 group.
3. The compound of claim 2 , wherein Y is a C 6 aryl substituted with:
a —NR q CONR q R r group,
a —NR t COOR u group,
a —NR v SO 2 R w group, or
a —NHR bb group, where R bb is —a —PO(OR x ) 2 group.
4. The compound of claim 1 , wherein Y is phenyl substituted at the para position.
5. The compound of claim 4 , wherein Y is phenyl substituted with a —NR q CONR q R r group at the para position.
6. The compound of claim 4 , wherein Y is phenyl substituted with a —NR t COOR u group at the para position.
7. The compound of claim 4 , wherein Y is phenyl substituted with a —NR v SO 2 R w group at the para position.
8. The compound of claim 4 , wherein Y is phenyl substituted with a —NHPO(OR x ) 2 group at the para position.
9. The compound of claim 1 , wherein Z is a C 1 to C 6 alkyl; —cyclopropyl; —cyclobutyl; —cyclopentyl; —cyclohexyl; —cyclopropylmethyl; —cyclobutylmethyl; or -cyclopentylmethyl.
10. The compound of claim 9 , wherein Z is a C 2 to C 5 alkyl; —cyclopropyl; —cyclobutyl; —cyclopentyl; —cyclopropylmethyl; or —cyclobutylmethyl.
11. The compound of claim 10 , wherein Z is cyclobutyl, cyclopropyl, cyclopropylmethyl, ethyl or cyclopentyl.
12. The compound of claim 1 , wherein R is hydrogen.
13. The compound of claim 1 , wherein R 1 is:
a hydrogen; or
an alkoxy group optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl group, or
a 5 or 6 membered heterocycle.
14. The compound of claim 1 , wherein R 2 is:
a hydrogen;
a halogen;
a hydroxy group;
a C 1 to C 6 alkyl group, optionally substituted with one or more halogen(s);
an amino group;
an alkoxy group optionally substituted with:
one or more halogen(s),
an —OCOR x group, where R x is as defined above,
an amino substituted with cyclopropyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl,
a 5 or 6 membered heteroaryl group, or
a C 6 to C 8 aryl group;
a —COOR x group; or
a cyclopropoxy.
15. The compound of claim 1 , wherein:
R 1 is a hydroxy group or an alkoxy group optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl group, or
a 5 or 6 membered heterocycle group; or
R 2 is a —OCOR x group, a —OR kk group, or an alkoxy group substituted with:
an —OCOR x group,
an amino substituted with cyclopropyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group substituted with a C 1 to C 6 alkyl;
a 5 or 6 membered heteroaryl group; or
a cyclopropoxy.
16. The compound of claim 15 , wherein R 2 is an alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
17. The compound of claim 16 , wherein R 2 is a C 1 to C 6 alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
18. The compound of claim 1 , wherein R 3 is a hydrogen.
19. The compound of claim 1 , wherein:
Y is a C 6 aryl substituted with:
a —NR q CONR q R r group,
a —NR t COOR u group,
a —NR v SO 2 R w group, or
a —NHPO(OR x ) 2 group;
R is hydrogen;
R 1 is a hydroxy group or an alkoxy group optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl group, or
a 5 or 6 membered heterocycle group; or
R 2 is a —OCOR x group, a —OR kk group, or an alkoxy group substituted with:
an —OCOR x group,
an amino substituted with cyclopropyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group substituted with a C 1 to C 6 alkyl;
a 5 or 6 membered heteroaryl group; or
a cyclopropoxy; and
R 3 is hydrogen.
20. The compound of claim 19 , wherein Y is a phenyl substituted with a —NR q CONR q R r group.
21. The compound of claim 20 , wherein:
Z is a C 1 to C 6 alkyl; —a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; —a cyclobutylmethyl; or —a cyclopentylmethyl; and
R 2 is an alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
22. The compound of claim 19 , wherein Y is a phenyl substituted with a —NR t COOR u group.
23. The compound of claim 22 , wherein:
Z is a C 1 to C 6 alkyl; —a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; —a cyclobutylmethyl; or —a cyclopentylmethyl; and
R 2 is an alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
24. The compound of claim 19 , wherein Y is a phenyl substituted with a —NR v SO 2 R w group.
25. The compound of claim 24 , wherein:
Z is a C 1 to C 6 alkyl; —a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; —a cyclobutylmethyl; or —a cyclopentylmethyl; and
R 2 is an alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
26. The compound of claim 19 , wherein Y is a phenyl substituted with a —NHPO(OR x ) 2 group.
27. The compound of claim 26 , wherein:
Z is a C 1 to C 6 alkyl; —a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; —a cyclobutylmethyl; or —a cyclopentylmethyl; and
R 2 is an alkoxy group optionally substituted with:
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl; or
a 5 or 6 membered heteroaryl group.
28. A compound selected from:
or a pharmaceutically acceptable salt thereof.
29. The compound of claim 28 which is selected from:
or a pharmaceutically acceptable salt thereof.
30. A pharmaceutical composition comprising:
(i) a compound of formula I
wherein:
X is:
a cyano group;
Y is:
a C 6 aryl, substituted with one or more of the following:
an alkoxy, optionally substituted with:
an alkoxy,
a hydroxy,
one or more halogen(s),
a 5 or 6 membered heterocycle, optionally substituted with:
a C 1 to C 6 alkyl, or
a hydroxy,
an amino group optionally substituted with one or more C 1 to C 6 alkyl(s), a —NR i SO 2 R x group, where R x is a C 1 to C 6 alkyl and R i is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR j COR k group, where R k is:
a C 1 to C 6 alkyl,
a hydrogen, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), and R j is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —N═N + ═N − group, or
a —COR 1 , where R 1 is a 5 or 6 membered heterocycle optionally substituted with a hydroxy,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s),
a nitro group,
a C 1 to C 6 alkyl group, optionally substituted with:
a —NHSO 2 R x group, where R x is as defined above, or
a —NR x SO 2 R x group, where R x is as defined above,
a haloalkoxy,
a halogen,
a hydroxy,
a —COOR x group, where R x is as defined above,
a —COR m group, where R m is:
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), where the C 1 to C 6 alkyls are optionally substituted with:
a hydroxy
a 5 or 6 membered heterocycle,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), or
an alkoxy,
a 3 to 7 membered heterocycle, optionally substituted with a C 1 to C 6 alkyl, optionally substituted with a dialkyl-amino, or
a —NHR n group, where R n is:
a —CH 2 CONH 2 , or
a C 6 to C 8 aryl optionally substituted with:
an alkyl,
one or more halogen(s),
a nitro group, or
one or more alkoxy(s),
a —NR o COR p group, where R p is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
an alkoxy, or
a C 6 to C 8 aryl,
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with a halogen,
a 5 or 6 membered heteroaryl optionally substituted with one or more C 1 to C 6 alkyl(s),
a hydrogen,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl,
a cyclopropylmethyl,
and where R o is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR q CONR q R r group, where R q is:
a hydrogen,
a C 1 to C 6 alkyl,
a haloalkyl,
a haloalkoxy, or
a —COR x group, where R x is as defined above, and where R r is:
a C 6 to C 8 aryl optionally substituted with:
a C 1 to C 6 alkyl,
a haloalkyl,
a —OR s group, where R s is a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a C 1 to C 6 alkyl optionally substituted with one or more of the following:
a halogen,
an alkenyl,
a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a —COOR x group, where R x is as defined above,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl;
a —NR t COOR u group, where R u is:
a C 1 to C 12 alkyl, optionally substituted with:
a C 6 to C 8 aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy,
an alkenyl,
an alkoxy,
an alkynyl,
a halogen, or
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with:
an alkoxy,
a halogen, or
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl,
a cyclopropylmethyl,
a cyclopropylethyl,
a cyclobutylmethyl,
a (1-methylcyclopropyl)methyl, or
a 1-methylcyclopentyl, and where R t is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR v SO 2 R w group, where R v is:
a hydrogen,
a —COR x , where R x is as defined above, or
a C 1 to C 6 alkyl, optionally substituted with:
a halogen,
a —COR x group, where R x is as defined above,
a —OCOR x group, where R x is as defined above,
a hydroxy, or
an alkoxy, and where R w is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
a haloalkyl,
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle,
a C 2 to C 6 alkenyl,
a mono-alkyl-amino or dialkyl-amino optionally substituted on alkyl with a halogen,
a 5 or 6 membered heterocycle,
a 5 or 6 membered heteroaryl optionally substituted with:
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle, or
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl,
a optionally substituted with a C 1 to C 6 alkyl, where R y is a C 1 to C 6 alkyl or hydrogen,
where R z is hydrogen or a C 1 to C 6 alkyl, optionally substituted with a C 6 to C 8 aryl,
a —SR x group, where R x is as defined above,
a —SO 2 R aa group, where R aa is:
a C 1 to C 6 alkyl,
an amino group,
a mono-alkyl-amino or dialkyl-amino group optionally substituted with a hydroxy
or a —COOR x group, where R x is as defined above,
a 5 or 6 membered heteroaryl,
a C 6 to C 8 aryl, or
a —NHR bb group, where R bb is:
a —C(═S)NH 2 group, or
a —PO(OR x ) 2 group, where R x is as defined above;
Z is:
a C 1 to C 6 alkyl optionally substituted with:
an alkoxy,
one or more halogen(s), or
a C 6 to C 8 aryl;
a C 2 to C 6 alkenyl;
a cyclopropyl;
a cyclobutyl;
a cyclopentyl;
a cyclohexyl;
a cyclopropylmethyl;
a cyclobutylmethyl; or
a cyclopentylmethyl;
R is a hydrogen, a halogen or an alkoxy;
R 1 is:
a hydrogen;
a hydroxy;
a halogen;
a haloalkyl;
a nitro group;
a 5 or 6 membered heteroaryl;
a 5 or 6 membered heterocycle;
an alkoxy optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle;
a C 6 to C 8 aryl optionally substituted with an alkoxy;
a —COR x group, where R x is as defined above; or
a C 1 to C 6 alkyl optionally substituted with a dialkyl-amino or a 5 or 6 membered heterocycle;
R 2 is:
a nitro group;
a hydrogen;
a halogen;
a hydroxy group;
a C 1 to C 6 alkyl group, optionally substituted with one or more halogen(s);
an amino group;
an alkoxy group optionally substituted with:
one or more halogen(s),
an —OCOR x group, where R x is as defined above,
an amino substituted with:
(i) —a cyclopropyl,
(ii) —a cyclobutyl,
(iii) —a cyclopentyl,
(iv) —a cyclohexyl, or
(v) —a cyclopropylmethyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl,
a 5 or 6 membered heteroaryl group, or
a C 6 to C 8 aryl group;
a —COOR x group, where R x is as defined above;
a haloalkyl;
an amide group optionally substituted with:
a hydroxy group, or
a C 6 to C 8 aryl;
a 5 or 6 membered heteroaryl;
a —OCOR x group, where R x is as defined above;
a —NHCOR jj group, where R jj is:
an alkoxy, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s);
a —OR kk group, where R kk is a 5 to 6 membered heteroaryl;
a —NHSO 2 R x group, where R x is as defined above;
—a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; or
—a cyclopropoxy;
R 3 is:
a hydrogen; or
—CH 2 OCOR x , and R x is as defined above;
or one or more pharmaceutically acceptable salt(s) thereof; and
(ii) one or more pharmaceutically acceptable excipient(s).
31. A method for treating a Hepatitis C viral (HCV) infection in a subject in need thereof, comprising administering to the subject one or more compound(s) of formula I or a pharmaceutical composition comprising one or more compound(s) of formula I
wherein:
X is:
a cyano group;
Y is:
a C 6 aryl, substituted with one or more of the following:
an alkoxy, optionally substituted with:
an alkoxy,
a hydroxy,
one or more halogen(s),
a 5 or 6 membered heterocycle, optionally substituted with:
a C 1 to C 6 alkyl, or
a hydroxy,
an amino group optionally substituted with one or more C 1 to C 6 alkyl(s),
a —NR i SO 2 R x group, where R x is a C 1 to C 6 alkyl and R i is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR j COR k group, where R k is:
a C 1 to C 6 alkyl,
a hydrogen, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), and R j is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —N═N + ═N − group, or
a —COR 1 , where R 1 is a 5 or 6 membered heterocycle optionally substituted with a hydroxy,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s),
a nitro group,
a C 1 to C 6 alkyl group, optionally substituted with:
a —NHSO 2 R x group, where R x is as defined above, or
a —NR x SO 2 R x group, where R x is as defined above,
a haloalkoxy,
a halogen,
a hydroxy,
a —COOR x group, where R x is as defined above,
a —COR m group, where R m is:
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), where the one or more C 1 to C 6 alkyl(s) is optionally substituted with:
a hydroxy
a 5 or 6 membered heterocycle,
an amino optionally substituted with one or more C 1 to C 6 alkyl(s), or
an alkoxy,
a 3 to 7 membered heterocycle, optionally substituted with a C 1 to C 6 alkyl, optionally substituted with a dialkyl-amino, or
a —NHR n group, where R n is:
a —CH 2 CONH 2 , or
a C 6 to C 8 aryl optionally substituted with:
an alkyl,
one or more halogen(s),
a nitro group, or
one or more alkoxy(s),
a —NR o COR p group, where R p is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
an alkoxy, or
a C 6 to C 8 aryl,
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with a halogen,
a 5 or 6 membered heteroaryl optionally substituted with one or more C 1 to C 6 alkyl(s),
a hydrogen,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl,
a cyclopropylmethyl,
and where R o is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR q CONR q R r group, where R q is:
a hydrogen,
a C 1 to C 6 alkyl,
a haloalkyl,
a haloalkoxy, or
a —COR x group, where R x is as defined above, and where R r is:
a C 6 to C 8 aryl optionally substituted with:
a C 1 to C 6 alkyl,
a haloalkyl,
a —OR s group, where R s is a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a C 1 to C 6 alkyl optionally substituted with one or more of the following:
a halogen,
an alkenyl,
a C 6 to C 8 aryl, or
a —COOR x group, where R x is as defined above,
a —COOR x group, where R x is as defined above,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl;
a —NR t COOR u group, where R u is:
a C 1 to C 12 alkyl, optionally substituted with:
a C 6 to C 8 aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy,
an alkenyl,
an alkoxy,
an alkynyl,
a halogen, or
a 5 or 6 membered heterocycle,
a C 6 to C 8 aryl, optionally substituted with:
an alkoxy,
a halogen, or
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle,
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl,
a cyclopropylmethyl,
a cyclopropylethyl,
a cyclobutylmethyl,
a (1-methylcyclopropyl)methyl, or
a 1-methylcyclopentyl, and where R t is:
a hydrogen,
a C 1 to C 6 alkyl,
a —COR x group, where R x is as defined above,
a haloalkyl, or
a haloalkoxy,
a —NR v SO 2 R w group, where R v is:
a hydrogen,
a —COR x , where R x is as defined above, or
a C 1 to C 6 alkyl, optionally substituted with:
a halogen,
a —COR x group, where R x is as defined above,
a —OCOR x group, where R x is as defined above,
a hydroxy, or
an alkoxy, and where R w is:
a C 1 to C 6 alkyl optionally substituted with:
a halogen,
a haloalkyl,
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle,
a C 2 to C 6 alkenyl,
a mono-alkyl-amino or dialkyl-amino optionally substituted on alkyl with a halogen,
a 5 or 6 membered heterocycle,
a 5 or 6 membered heteroaryl optionally substituted with:
a C 1 to C 6 alkyl,
a 5 or 6 membered heterocycle, or
a cyclopropyl,
a cyclobutyl,
a cyclopentyl,
a cyclohexyl, or
a cyclopropylmethyl,
a optionally substituted with a C 1 to C 6 alkyl, where R y is a C 1 to C 6 alkyl or hydrogen,
where R z is hydrogen or a C 1 to C 6 alkyl, optionally substituted with a C 6 to C 8 aryl,
a —SR x group, where R x is as defined above,
a —SO 2 R aa group, where R aa is:
a C 1 to C 6 alkyl,
an amino group,
a mono-alkyl-amino or dialkyl-amino group optionally substituted with a hydroxy or a —COOR x group, where R x is as defined above,
a 5 or 6 membered heteroaryl,
a C 6 to C 8 aryl, or
a —NHR bb group, where R bb is:
a —C(═S)NH 2 group, or
a —PO(OR x ) 2 group, where R x is as defined above;
Z is:
a C 1 to C 6 alkyl optionally substituted with:
an alkoxy,
one or more halogen(s), or
a C 6 to C 8 aryl;
a C 2 to C 6 alkenyl;
a cyclopropyl;
a cyclobutyl;
a cyclopentyl;
a cyclohexyl;
a cyclopropylmethyl;
a cyclobutylmethyl; or
a cyclopentylmethyl;
R is a hydrogen, a halogen or an alkoxy;
R 1 is:
a hydrogen;
a hydroxy;
a halogen;
a haloalkyl;
a nitro group;
a 5 or 6 membered heteroaryl;
a 5 or 6 membered heterocycle;
an alkoxy optionally substituted with:
one or more halogen(s),
a C 6 to C 8 aryl, or
a 5 or 6 membered heterocycle;
a C 6 to C 8 aryl optionally substituted with an alkoxy;
a —COR x group, where R x is as defined above; or
a C 1 to C 6 alkyl optionally substituted with a dialkyl-amino or a 5 or 6 membered heterocycle;
R 2 is:
a nitro group;
a hydrogen;
a halogen;
a hydroxy group;
a C 1 to C 6 alkyl group, optionally substituted with one or more halogen(s);
an amino group;
an alkoxy group optionally substituted with:
one or more halogen(s),
an —OCOR x group, where R x is as defined above,
an amino substituted with:
(i) —a cyclopropyl,
(ii) —a cyclobutyl,
(iii) —a cyclopentyl,
(iv) —a cyclohexyl, or
(v) —a cyclopropylmethyl,
a dialkyl-amino optionally substituted on alkyl with an alkoxy,
a 5 or 6 membered heterocycle group optionally substituted with a C 1 to C 6 alkyl,
a 5 or 6 membered heteroaryl group, or
a C 6 to C 8 aryl group;
a —COOR x group, where R x is as defined above;
a haloalkyl;
an amide group optionally substituted with:
a hydroxy group, or
a C 6 to C 8 aryl;
a 5 or 6 membered heteroaryl;
a —OCOR x group, where R x is as defined above;
a —NHCOR jj group, where R jj is:
an alkoxy, or
an amino optionally substituted with one or more C 1 to C 6 alkyl(s);
a —OR kk group, where R kk is a 5 to 6 membered heteroaryl; or
a —NHSO 2 R x group, where R x is as defined above;
R 3 is:
a hydrogen;
—CH 2 OCOR x , and R x is as defined above;
—a cyclopropyl; —a cyclobutyl; —a cyclopentyl; —a cyclohexyl; —a cyclopropylmethyl; or
—a cyclopropoxy; or
one or more pharmaceutically acceptable salt(s) thereof.