Methods for treating hepatitis C

1. A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein:

X is -cyano;

Y is -aryl substituted with one or more of the following:

(1)-alkoxy optionally substituted with:

(i) -alkoxy,

(ii) -hydroxy,

(iii) -one or more halogen(s),

(iv) -5 or 6 membered heterocycle, optionally substituted with: —C 1 to C 6 alkyl, or -hydroxy,

(v) -amino optionally substituted with one or more C 1 to C 6 alkyl(s),

(vi) —NR i SO 2 R x , where R x is a C 1 to C 6 alkyl and R i is: -hydrogen, —C 1 to C 6 alkyl, —COR x , where R x is as defined above, -haloalkyl, or -haloalkoxy,

(vii) —NR j COR k , where R k is: —C 1 to C 6 alkyl, -hydrogen, or -amino optionally substituted with one or more C 1 to C 6 alkyl(s), and R j is: -hydrogen, —C 1 to C 6 alkyl, —COR x , where R x is as defined above, -haloalkyl, or -haloalkoxy,

(iii) —N═N + ═N − , or (ix) —COR 1 , where R 1 is a 5 or 6 membered heterocycle optionally substituted with a hydroxy,

(2)-amino optionally substituted with one or more C 1 to C 6 alkyl(s), cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cyclopropylmethyl,

(3) —C 1 to C 6 alkyl, optionally substituted with: —NHSO 2 R x , where R x is as defined above, or —NRSO 2 R x , where R x is as defined above,

(4) -haloalkoxy,

(5) -halogen,

(6) -hydroxy,

(7) —COOR x , where R x is as defined above,

(8) —COR m , where R m is:

(i) -amino optionally substituted with:

(a) one or more C 1 to C 6 alkyl(s), where the one or more C 1 to C 6 alkyl(s) are optionally substituted with: -hydroxy, -5 or 6 membered heterocycle, -amino optionally substituted with one or more C 1 to C 6 alkyl(s), or -alkoxy,

(b) -cyclopropyl,

(c) -cyclobutyl,

(d) -cyclopentyl,

(e) -cyclohexyl, or

(f) -cyclopropylmethyl,

(ii) -3 to 7 membered heterocycle, optionally substituted with a C 1 to C 6 alkyl, optionally substituted with a dialkyl-amino, or

(iii) —NHR n , where R n is: —CH 2 CONH 2 , or -aryl optionally substituted with: -alkyl, -one or more halogen(s), -nitro, or -one or more alkoxy(s),

(9) —NR o COR p ,

where R p is:

(i) —C 1 to C 6 alkyl optionally substituted with: -halogen, -alkoxy, or -aryl,

(ii) -5 or 6 membered heterocycle,

(iii) -aryl, optionally substituted with a halogen,

(iv) -5 or 6 membered heteroaryl optionally substituted with one or more C 1 to C 6 alkyl(s),

(v) -hydrogen,

(vi)

(vii) -cyclopropyl,

(viii) -cyclobutyl,

(ix) -cyclopentyl,

(x) -cyclohexyl, or

(xi) -cyclopropylmethyl,

and where R o is:

(i) -hydrogen,

(ii) —C 1 to C 6 alkyl,

(iii) —COR x , where R x is as defined above,

(iv) -haloalkyl, or

(v) -haloalkoxy,

(10) —NR q CONR q R r ,

where R q is:

(i) -hydrogen,

(ii) —C 1 to C 6 alkyl,

(iii) -haloalkyl,

(iv) -haloalkoxy, or

(v) —COR x , where R x is as defined above,

and where R 1 is:

(i) -aryl optionally substituted with:

—C 1 to C 6 alkyl, -haloalkyl, —OR s , where R s is aryl, or —COOR x , where R x is as defined above,

(ii) —C 1 to C 6 alkyl optionally substituted with one or more of the following: -halogen, -alkenyl, -aryl, or —COOR x , where R x is as defined above,

(iii) —COOR x , where R x is as defined above,

(iv) -cyclopropyl,

(v) -cyclobutyl,

(vi) -cyclopentyl,

(vii) -cyclohexyl, or

(viii) -cyclopropylmethyl;

(11) —NR t COOR u ,

where R u is:

(i) —C 1 to C 12 alkyl, optionally substituted with:

 (a) -aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy,

 (b) -alkenyl,

 (c) -alkoxy,

 (d) -alkynyl,

 (e) -halogen,

 (f) -5 or 6 membered heterocycle, or

 (g) -5 or 6 membered heteroaryl,

(ii) aryl, optionally substituted with: -alkoxy, -halogen, or —C 1 to C 6 alkyl,

(iii) -5 or 6 membered heterocycle,

(iv) -cyclopropyl,

(v) -cyclobutyl,

(vi) -cyclopentyl,

(vii) -cyclohexyl,

(viii) -cyclopropylmethyl,

(ix) -cyclopropylethyl,

(x) -cyclobutylmethyl,

(xi) -1-methylcyclobutyl,

(xii) -2-cyclobutylpropanyl,

(xiii) -(1R)-1,3,3-trimethylbicyclo[2.2.1]heptanyl,

(xiv) -(2S)-2,6,6-trimethylbicyclo[3.1.1]heptanyl,

(xv) -adamantyl,

(xvi) -cyclobutylethyl,

(xvii) -(1-methylcyclopropyl)methyl, or

(xviii) -1-methylcyclopentyl,

and where R t is:

(i) -hydrogen,

(ii) —C 1 to C 6 alkyl,

(iii) —COR x , where R x is as defined above,

(iv) -haloalkyl,

(v) -haloalkoxy,

(vi) -cyclopropyl,

(vii) -cyclobutyl,

(viii) -cyclopentyl,

(ix) -cyclohexyl, or

(x) -cyclopropylmethyl,

(12) —NR v SO 2 R w ,

where R v is:

(i) -hydrogen,

(ii) —COR x , where R x is as defined above, or

(iii) —C 1 to C 6 alkyl, optionally substituted with: -halogen, —COR x , where R x is as

defined above, —OCOR x , where R x is as defined above, -hydroxy, or -alkoxy, and where R w is:

(i) —C 1 to C 6 alkyl optionally substituted with: -halogen, -haloalkyl,

-aryl, or -5 or 6 membered heterocycle,

(ii) —C 2 to C 6 alkenyl,

(iii) mono- or dialkyl-amino optionally substituted on alkyl with a halogen, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl,

(iv) -5 or 6 membered heterocycle,

(v) -5 or 6 membered heteroaryl optionally substituted with: —C 1 to C 6 alkyl, -5 or 6 membered heterocycle, or

(vi) -cyclopropyl,

(vii) -cyclobutyl,

(viii) -cyclopentyl,

(ix) -cyclohexyl,

(x) -cyclopropylmethyl,

(xi) -cyclobutylmethyl,

(xii) -1-methylcyclopropyl,

(xiii) -1-ethylcyclopropyl, or

(xiv) -cyclopropylethyl,

where R z is hydrogen or a C 1 to C 6 alkyl, optionally substituted with aryl,

(20) —SR x , where R x is as defined above,

(21) —SO 2 R aa , where R aa is:

(i) —C 1 to C 6 alkyl,

(ii) -amino,

(iii) -mono- or dialkyl-amino optionally substituted on alkyl with a hydroxy or a —COOR x , where R x is as defined above,

(iv) -5 or 6 membered heteroaryl,

(v) -cyclopropylamino,

(vi) -cyclobutylamino, or

(vii) -cyclopentylamino,

(22) -aryl, or

(23) —NHR bb , where R bb is:

(iii) —C(═S)NH 2 , or

(iv) —PO(OR x ) 2 , where R x is as defined above;

Z is:

(a) —C 1 to C 6 alkyl optionally substituted with:

(1) -alkoxy,

(2) -one or more halogen(s), or

(3) -aryl;

(b) —C 2 to C 6 alkenyl;

(c) -cyclopropyl;

(d) -cyclobutyl;

(e) -cyclopentyl;

(f) -cyclohexyl;

(g) -cyclopropylmethyl;

(h) -cyclopropylethyl;

(i) -cyclobutylmethyl; or

(j) -cyclopentylmethyl;

R is hydrogen, halogen or alkoxy;

R 1 is:

(a) -hydrogen;

(b) -hydroxy;

(c) -halogen;

(d) -haloalkyl;

(e) -nitro;

(f) -5 or 6 membered heteroaryl;

(g) -5 or 6 membered heterocycle;

(h) -alkoxy optionally substituted with:

(1) -one or more halogen(s),

(2) -aryl, or

(3) -5 or 6 membered heterocycle;

(i) -aryl optionally substituted with an alkoxy;

(j) —COR x , where R x is as defined above; or

(k) —C 1 to C 6 alkyl optionally substituted with a dialkyl-amino or a 5 or 6 membered heterocycle;

R 2 is:

(a) -nitro;

(b) -hydrogen;

(c) -halogen;

(d) -hydroxy;

(e) —C 1 to C 6 alkyl, optionally substituted with one or more halogen(s);

(f) -amino;

(g) -alkoxy optionally substituted with:

(1) -one or more halogen(s),

(2) -OCOR x , where R x is as defined above,

(3) -amino substituted with cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl

(4) -dialkyl-amino optionally substituted on alkyl with an alkoxy,

(5) -5 or 6 membered heterocycle optionally substituted with a C 1 to C 6 alkyl,

(6) -5 or 6 membered heteroaryl, or

(7) -aryl;

(h) —COOR x , where R x is as defined above;

(i) -haloalkyl;

(j) -amide optionally substituted with:

(1) -hydroxy, or

(2) -aryl;

(k) -5 or 6 membered heteroaryl;

(l) —OCOR x , where R x is as defined above;

(m) —NHCOR jj , where R jj is:

(1) -alkoxy, or

(2) -amino optionally substituted with one or more C 1 to C 6 alkyl(s);

(n) —OR kk , where R kk is a 5 to 6 membered heteroaryl;

(o) —NHSO 2 R x , where R x is as defined above;

(p) -cyclopronyl;

(q) -cyclobutyl;

(r) -cyclopentyl;

(s) -cyclohexyl;

(t) -cyclopropoxy;

(u) -cyclobutoxy;

(v) -cyclopropylmethoxy; or

(w) -cyclopentoxy; and

R 3 is:

(a) -hydrogen; or

(b) —CH 2 OCOR x , and R x is as defined above.

2. The compound of claim 1 , wherein:

Y is aryl substituted with one or more of the following:

(1) -amino optionally substituted with one or more C 1 to C 6 alkyl(s) or cyclopropylmethyl,

(2) -C 1 to C 6 alkyl, optionally substituted with a —NHSO 2 R x ,

(3) —NR o COR p , where R p is: (i) —C 1 to C 6 alkyl optionally substituted with: halogen, or -aryl, (ii) -5 or 6 membered heterocycle, (iii) -cyclopropyl or (iv) -cyclobutyl and where R o is a hydrogen,

(4) —NR q CONR q R r , where R q is: (i) -hydrogen, or (ii) —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: (i) -halogen, (ii) -alkenyl, or (iii) -aryl; (b) -cyclopropyl; (c) -cyclobutyl; (d) -cyclopentyl or (e) -cyclohexyl,

(5) —NR t COOR u , where R u is: (i) —C 1 to C 12 alkyl, optionally substituted with: (a) -aryl optionally substituted with a C 1 to C 6 alkyl or an alkoxy, (b) -alkenyl, (c) -alkoxy, (d) -alkynyl, (e) -halogen, of (f) -5 or 6 membered heterocycle, or (g) -5 or 6 membered heteroaryl, (ii) -aryl, optionally substituted with an alkoxy, (iii) -5 or 6 membered heterocycle, (iv) -cyclobutyl, (v) -cyclopentyl, (vi) -cyclopropylmethyl, (vii) -cyclopropylethyl, (viii) -cyclobutylmethyl, (ix) -1-methylcyclobutyl, (x) -2-cyclobutylpropanyl, (xi) -(1R)-1,3,3-trimethylbicyclo[2.2.1]heptanyl, (xii) -(2S)-2,6,6-trimethylbicyclo[3.1.1]heptanyl, (xiii) -adamantyl, (xiv) -cyclobutylethyl, (xv) -(1-methylcyclopropyl)methyl, or (xvi) -1-methylcyclopentyl; and where R t is: (i) -hydrogen, (ii) —C 1 to C 6 alkyl, or (iii) -cyclopropylmethyl, (6) —NR v SO 2 R w , where R v is a hydrogen, or —C 1 to C 6 alkyl, and where R w is (i) a C 1 to C 6 alkyl optionally substituted with a halogen, (ii) monoalkyl-amino optionally substituted on alkyl with cyclopropyl, (iii) -cyclopropyl, (iv) -cyclobutyl, (v) -cyclopentyl, (vi) -cyclobutylmethyl, (vii) -1-methylcyclopropyl, or (viii) -1-ethylcyclopropyl;

where R z is a C 1 to C 6 alkyl;

(13) —SO 2 R aa , where R aa is (i) -amino, (ii) monoalkyl-amino, (iii) -cyclopropylamino, (iv) -cyclobutylamino or (v) -cyclopentylamino; or

(14) —NHR bb , where R bb is a —PO(OR x ) 2 .

3. The compound of claim 1 , wherein:

Y is aryl substituted with:

(1) -a —NR q CONR q R r ,

(2) -a —NR t COOR u ,

(3) -a —NR v SO 2 R w , or

(4) -a —NHPO(OR x ) 2 ;

Z is (a) -a C 1 to C 6 alkyl optionally substituted with

(1) -an alkoxy, or

(2) -one or more halogen(s),

(b) -a C 2 to C 6 alkenyl;

(c) -cyclopropyl;

(d) -cyclobutyl;

(e) -cyclopentyl;

(f) -cyclopropylmethyl;

(g) -cyclopropylethyl;

(h) -cyclobutylmethyl; or

(i) -cyclopentylmethyl;

R is hydrogen;

R 1 is (a) hydroxy or (b) an alkoxy group optionally substituted with:

(1) -one or more halogen(s),

(2) -aryl group, or

(3) -a 5 or 6 membered heterocycle group; or

R 2 is

(a) —OCOR x ,

(b) a —OR kk ,

(c) an alkoxy substituted with:

(1) —OCOR x ,

(2) -amino substituted with cyclopropyl,

(3) -a dialkyl-amino optionally substituted on alkyl with an alkoxy,

(4) -a 5 or 6 membered heterocycle substituted with a C 1 to C 6 alkyl; or

(5) -a 5 or 6 membered heteroaryl;

(d) -cyclopropyl;

(e) -cyclopropoxy;

(f) -cyclobutoxy;

(g) -cyclopropylmethoxy; or

(h) -cyclopentoxy; and

R 3 is hydrogen.

4. The compound of claim 1 , wherein:

Y is -aryl, substituted with one or more of the following:

(1) —C 1 to C 6 alkyl;

(2) -amino optionally substituted with one or more C 1 to C 6 alkyl(s) or cyclopropylmethyl;

(3) -halogen;

(4) -hydroxy;

(5) —COR m , where R m is an amino optionally substituted with one or more C 1 to C 6 alkyl(s), or cyclobutyl;

(6) —NR o COR p , where R p is (i) a C 1 to C 6 alkyl optionally substituted with an alkoxy, or aryl, (ii) 5 or 6 membered heterocycle, (iii) cyclopropyl, or (iv) cyclobutyl, and where R o is a hydrogen;

(7) —NR q CONR q R r , where R q is hydrogen and where R r is (a) a C 1 to C 6 alkyl, (b) -cyclopropyl, (c) -cyclobutyl, (d) -cyclopentyl or (e) -cyclohexyl;

(8) —NR t COOR u , where R t is hydrogen or -cyclopropylmethyl, and where R u is (a) a C 1 to C 12 alkyl, optionally substituted with: (i) -aryl; (ii) -halogen; (iii) -5 or 6 membered heterocycle, or (iv) -5 or 6 membered heteroaryl; (b) -cyclobutyl, (c) -cyclopentyl, (d) -cyclopropylmethyl, (e) -cyclopropylethyl, (f) -cyclobutylmethyl, (g) -1-methylcyclobutyl, (h) -2-cyclobutylpropanyl, (i) -(1R)-1,3,3-trimethylbicyclo[2.2.1]heptanyl, (j) -(2S)-2,6,6-trimethylbicyclo[3.1.1]heptanyl, (k) -adamantyl, (l) -cyclobutylethyl, (m) -(1 methylcyclopropyl)methyl, or (n) -1-methylcyclopentyl;

(9) —NR v SO 2 R w , where R v is hydrogen and where R w is (i) —C 1 to C 6 alkyl; (ii) mono- or dialkyl-amino optionally substituted on alkyl with cyclopropyl, (iii) -cyclopropyl, (iv) -cyclobutyl, (v) -cyclopentyl, (vi) -cyclopropylmethyl, (vii) -cyclobutylmethyl, (viii) -1-methylcyclopropyl (ix) -1-ethylcyclopropyl, or (x) -cyclopropylethyl;

where R z is hydrogen or a C 1 to C 6 alkyl;

(13) —SO 2 R aa , where R aa is: (i) -amino; or (ii) mono- or dialkyl amino;

(iii) -cyclopropylamino; (iv) -cyclobutylamino or (v) -cyclopentylamino; or

(14) —NHR bb , where R bb is a —PO(OR x ) 2 , where R x is as defined above;

Z is

(a) —C 1 to C 6 alkyl;

(b) -cyclopropyl;

(c) -cyclobutyl;

(d) -cyclopentyl;

(e) -cyclopropylmethyl;

(f) -cyclopropylethyl;

(g) -cyclobutylmethyl; or

(h) -cyclopentylmethyl;

R is hydrogen;

R 1 is:

(a) -hydrogen;

(b) -5 or 6 membered heterocycle; or

(c) -alkoxy optionally substituted with: -one or more halogen(s); or -5 or 6 membered heterocycle;

R 2 is:

(a) -hydrogen;

(b) -hydroxy;

(c) —C 1 to C 6 alkyl, optionally substituted with one or more halogen(s);

(d) -alkoxy optionally substituted with:

(1) -one or more halogen(s);

(2) -amino substituted with cyclopropyl;

(3) -5 or 6 membered heterocycle optionally substituted with a C 1 to C 6 alkyl; or

(4) -5 or 6 membered heteroaryl;

(e) -cyclopropyl;

(f) -cyclopropoxy;

(g) -cyclobutoxy;

(h) -cyclopropylmethoxy;

(i) -cyclopentoxy;

(j) —COOR x , where R x is as defined above;

(k) -amide;

(l) -5 or 6 membered heteroaryl; or

(m) —OR kk , where R kk is a 5 to 6 membered heteroaryl; and

R 3 is hydrogen.

5. A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

7. A method for treating a viral infection in a subject in need thereof comprising administering an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to the subject, wherein said viral infection is a Hepatitis C viral infection.