Viral inhibitors

1. A compound having the general formula (A),

wherein:

the dotted lines represent at least 3, optionally 4 double bonds, provided that no two double bonds are adjacent to one another;

A is —N═ and the other one A is CR 26 ;

R 1 is selected from hydrogen, aryl, heterocycle, C 1 -C 10 alkoxy, thioalkyl, C 1 -C 10 alkyl-amino, C 1 -C 10 dialkyl-amino, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, and C 4-10 cycloalkynyl, wherein each are optionally substituted with 1 or more R 6 ;

Y is selected from a single bond, O, S(O) m , NR 10 , alkylene, C 2-10 alkenylene, or C 2-10 alkynylene, wherein 1 to 3-C(H)═, —C(≡) or —CH 2 — groups of each alkylene, alkenylene or alkynylene optionally are independently replaced with a heteroatom or heteroatom group selected from —O—, ═O, —OR 27 , —S—, ═S, —SR 27 , —NR 27 , —N(R 27 ) 2 , where R 27 independently is hydrogen, C 1-18 alkyl, C 2-18 alkenyl, or C 2-18 alkynyl;

provided that YR 1 is not hydrogen or C 1-6 alkyl;

R 2 and R 4 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, halogen, —OH, —CN, —NO 2 , —NR 7 R 8 , haloalkyloxy, haloalkyl, —C(═O)R 9 , —C(═S)R 9 , SH, aryl, aryloxy, arylthio, arylalkyl, C 1-18 hydroxyalkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyloxy, C 3-10 cycloalkylthio, C 3-10 cycloalkenyl, C 3-10 cycloalkynyl, or heterocycle;

X is absent or is selected from hydrogen, alkylene, C 2-10 alkenylene or C 2-10 alkynylene, wherein 1 to 3 —C(H)═, —C(≡) or —CH 2 — groups of each alkylene, alkenylene or alkynylene optionally are independently replaced with a heteroatom or heteroatom group selected from —O—, ═O, —OR 27 , —S—, ═S, —SR 27 , —NR 27 , —N(R 27 ) 2 , where R 27 independently is hydrogen, C 1-18 alkyl, C 2-18 alkenyl, or C 2-18 alkynyl;

m is any integer from 0 to 2;

R 3 is absent or is selected from hydrogen, aryl, aryloxy, arylthio, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl-N(R 10 )—, or an aromatic heterocycle, where each said substituent is optionally substituted with 1 or more R 17 , provided that for cycloalkenyl the double bond is not adjacent to a nitrogen;

R 5 is selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, halogen, —OH, —CN, —NO 2 , —NR 7 R 8 , haloalkyloxy, haloalkyl, —C(═O)R 9 , —C(═O)OR 9 , —C(═S)R 9 , SH, aryl, aryloxy, arylthio, arylalkyl, C 1-18 hydroxyalkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyloxy, C 3-10 cycloalkylthio, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, or heterocycle;

R 6 is selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, C 1-18 alkylsulfoxide, C 1-18 alkylsulfone, C 1-18 halo-alkyl, C 2-18 halo-alkenyl, C 2-18 halo-alkynyl, C 1-18 halo-alkoxy, C 1-18 halo-alkylthio, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, halogen, OH, CN, cyanoalkyl, —CO 2 R 18 , NO 2 , —NR 7 R 8 , C 1-18 haloalkyl, C(═O)R 18 , C(═S)R 18 , SH, aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, aryl(C 1-18 )alkyl, aryl(C 1-18 )alkyloxy, aryl(C 1-18 )alkylthio, heterocycle and C 1-18 hydroxyalkyl, where each is optionally substituted with 1 to 3 R 19 ;

R 7 and R 8 are independently selected from hydrogen, C 1-18 alkyl, C 1-18 alkenyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, heterocycle, —C(═O)R 12 ; —C(═S)R 12 , an amino acid residue linked through a carboxyl group thereof, or R 7 and R 8 are taken together with the nitrogen to form a heterocycle;

R 9 and R 18 are independently selected from hydrogen, OH, C 1-18 alkyl, C 2-18 alkenyl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, C 1-18 alkoxy, —NR 15 R 16 , an amino acid residue linked through an amino group of the amino acid, CH 2 OCH(═O)R 9a , or CH 2 OC(═O)OR 9a where R 9a is C 1 -C 12 alkyl, C 6 -C 20 aryl, C 6 -C 20 alkylaryl or C 6 -C 20 aralkyl;

R 10 and R 11 are independently selected from the group consisting of hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, aryl, —C(═O)R 12 , heterocycle, or an amino acid residue;

R 12 is selected from the group consisting of hydrogen, C 1-18 alkyl, C 2-18 alkenyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, or an amino acid residue;

R 15 and R 16 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, or an amino acid residue;

R 17 is independently selected from the group consisting of hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, C 1-18 alkylsulfoxide, C 1-18 alkylsulfone, C 1-18 halogenated alkyl, C 2-18 halogenated alkenyl, C 2-18 halogenated alkynyl, C 1-18 halogenated alkoxy, C 1-18 halogenated alkylthio, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, halogen, OH, CN, CO 2 H CO 2 R 18 , NO 2 , NR 7 R 8 , haloalkyl, C(═O)R 18 , C(═S)R 18 , SH, aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl, arylalkyloxy, arylalkylthio, heterocycle, C 1-18 hydroxyalkyl, where each of said aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl, arylalkyloxy, arylalkylthio, heterocycle, or C 1-18 hydroxyalkyl is optionally substituted with 1 or more R 19 ;

R 19 is selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 2-18 alkenyloxy, C 2-18 alkynyloxy, C 1-18 alkylthio, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, C 4-10 cycloalkynyl, halogen, —OH, —CN, cyanoalkyl, —NO 2 , —NR 20 R 21 , C 1-18 haloalkyl, C 1-18 haloalkyloxy, —C(═O)R 18 , —C(═O)OR 18 , —OalkenylC(═O)OR 18 , —OalkylC(═O)NR 20 R 21 , —OalkylOC(═O)R 18 , —C(═S)R 18 , SH, —C(═O)N(C 1-6 alkyl), —N(H)S(O)(O)(C 1-6 alkyl), aryl, heterocycle, C 1-18 alkylsulfone, arylsulfoxide, arylsulfonamide, aryl(C 1-18 )alkyloxy, aryloxy, aryl(C 1-18 alkyl)oxy, arylthio, aryl(C 1-18 )alkylthio or aryl(C 1-18 )alkyl, where each is optionally substituted with 1 to 3 of ═O, NR 20 R 21 , ON, C 1-18 alkoxy, heterocycle, C 1-18 haloalkyl, heterocycle alkyl, heterocycle connected to R 17 by alkyl, alkoxyalkoxy or halogen;

R 20 and R 21 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, —C(═O)R 12 , or —C(═S)R 12 ;

R 26 is independently selected from hydrogen, and C 3-10 cycloalkyl;

and salts, tautomers, and stereoisomers thereof.

2. The compound of claim 1 , wherein Y is a single bond and R 1 is phenyl substituted with 1 to 3 R 6 .

3. The compound according to claim 1 , wherein X is C1-C3 alkylene and R 3 is heterocycle independently substituted with 1 or 2 R 17 .

4. The compound of claim 3 wherein R 17 independently is substituted with 1 or 2 R 19 .

5. The compound of claim 4 wherein Y is a bond.

6. The compound of claim 4 wherein R 1 is aryl independently substituted with 1 or 2 R 6 .

7. The compound of claim 4 wherein R 2 , R 4 and R 5 are hydrogen.

8. The compound of claim 4 wherein X is methylene.

9. The compound of claim 4 wherein R 3 is a five membered heteroaryl containing 1 to 3 N, O and/or S ring atoms.

10. The compound of claim 4 wherein R 3 is isoxazolyl or pyridizinyl.

11. The compound of claim 4 wherein R 17 independently is aryl.

12. The compound of claim 11 wherein aryl is phenyl.

13. The compound of claim 12 wherein R 19 is independently halo or C1-C6 haloalkyl.

14. The compound of claim 1 wherein X is methylene and R 3 is isoxazole substituted with phenyl substituted with 1 or 2 R 19 independently selected from halo and C1-C6 haloalkyl.

15. The compound of claim 1 wherein R 26 is C 3 -C 6 cycloalkyl.

16. The compound of claim 4 wherein R 3 is a six membered heteroaryl containing 1 or 2 N ring atoms.

17. A compound having the general formula:

wherein:

one A is —N═, and the other A is ═CR 26 ;

R 1 is phenyl or an aromatic heterocycle with 5 or 6 ring atoms with either 1, 2 or 3 N, O or S atoms in the ring, and wherein each is optionally substituted with 1 or more R 6 ;

R 2 and R 4 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, halogen, —OH, —CN, —NO 2 , —NR 7 R 8 , haloalkyloxy, haloalkyl, —C(═O)R 9 , —C(═S)R 9 , SH, aryl, aryloxy, arylthio, arylalkyl, C 1-18 hydroxyalkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyloxy, C 3-10 cycloalkylthio, C 3-10 cycloalkenyl, C 3-10 cycloalkynyl, or heterocycle;

X is C 1 -C 10 alkylene, wherein 1 to 3 —CH 2 — groups optionally are independently replaced with a heteroatom or heteroatom group selected from —O—, ═O, —OR 27 , —NR 27 , and —N(R 27 ) 2 , where R 27 independently is hydrogen, C 1-18 alkyl, C 2-18 alkenyl, or C 2-18 alkynyl;

R 3 is absent or is selected from hydrogen, aryl, and an aromatic heterocycle, where the aryl or heterocyclic groups are each optionally substituted with 1 or more R 17 ;

R 5 is selected from hydrogen; C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, halogen, —OH, —CN, —NO 2 , —NR 7 R 8 , haloalkyloxy, haloalkyl, —C(═O)R 9 , —C(═O)OR 9 , —C(═S)R 9 , SH, aryl, aryloxy, arylthio, arylalkyl, C 1-18 hydroxyalkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyloxy, C 3-10 cycloalkylthio, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, or heterocycle;

R 6 is selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, C 1-18 alkylsulfoxide, C 1-18 alkylsulfone, C 1-18 halo-alkyl, C 2-18 halo-alkenyl, C 2-18 halo-alkynyl, halo-alkoxy, C 1-18 halo-alkylthio, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, halogen, OH, CN, cyanoalkyl, —CO 2 R 18 , NO 2 , —NR 7 R 8 , C 1-18 haloalkyl, C(═O)R 18 , C(═S)R 18 , SH, aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, aryl(C 1-18 )alkyl, aryl(C 1-18 )alkyloxy, aryl(C 1-18 )alkylthio, heterocycle and C 1-18 hydroxyalkyl, where each is optionally substituted with 1 to 3 R 19 ;

R 7 and R 8 are independently selected from hydrogen, C 1-18 alkyl, C 1-18 alkenyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, heterocycle, —C(═O)R 12 ; —C(═S)R 12 , an amino acid residue linked through a carboxyl group thereof, or R 7 and R 8 are taken together with the nitrogen to form a heterocycle;

R 9 and R 18 are independently selected from hydrogen, OH, C 1-18 alkyl, C 2-18 alkenyl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, C 1-18 alkoxy, —NR 15 R 16 , aryl, an amino acid residue linked through an amino group of the amino acid, CH 2 OCH(═O)R 9a , or CH 2 OC(═O)OR 9a where R 9a is C 1 -C 12 alkyl, C 6 -C 20 aryl, C 6 -C 20 alkylaryl or C 6 -C 20 aralkyl;

R 12 is selected from the group consisting of hydrogen, C 1-18 alkyl, C 2-18 alkenyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, or an amino acid residue;

R 15 and R 16 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, or an amino acid residue;

R 17 is independently selected from the group consisting of hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 1-18 alkylthio, C 1-18 alkylsulfoxide, C 1-18 alkylsulfone, C 1-18 halogenated alkyl, C 2-18 halogenated alkenyl, C 2-18 halogenated alkynyl, C 1-18 halogenated alkoxy, C 1-18 halogenated alkylthio, C 3-10 cycloalkyl, C 3-10 cycloalkenyl, C 7-10 cycloalkynyl, halogen, OH, CN, CO 2 H, CO 2 R 18 , NO 2 , NR 7 R 8 , haloalkyl, C(═O)R 18 , C(═S)R 18 , SH, aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl, arylalkyloxy, arylalkylthio, heterocycle, C 1-18 hydroxyalkyl, where each of said aryl, aryloxy, arylthio, arylsulfoxide, arylsulfone, arylsulfonamide, arylalkyl, arylalkyloxy, arylalkylthio, heterocycle, or C 1-18 hydroxyalkyl is optionally substituted with 1 or more R 19 ;

R 19 is selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, C 1-18 alkoxy, C 2-18 alkenyloxy, C 2-18 alkynyloxy, C 1-18 alkylthio, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, C 4-10 cycloalkynyl, halogen, —OH, —CN, cyanoalkyl, —NO 2 , —NR 20 R 21 , C 1-18 haloalkyl, C 1-18 haloalkyloxy, —C(═O)R 18 , —C(═O)OR 18 , —OalkenylC(═O)OR 18 , —OalkylC(═O)NR 20 R 21 , —OalkylOC(═O)R 18 , —C(═S)R 18 , SH, —C(═O)N(C 1-6 alkyl), —N(H)S(O)(O)(C 1-6 alkyl), aryl, heterocycle, C 1-18 alkylsulfone, arylsulfoxide, arylsulfonamide, aryl(C 1-18 )alkyloxy, aryloxy, aryl(C 1-18 alkyl)oxy, arylthio, aryl(C 1-18 )alkylthio or aryl(C 1-18 )alkyl, where each is optionally substituted with 1 to 3 of ═O, NR 20 R 21 , CN, C 1-18 alkoxy, heterocycle, C 1-18 haloalkyl, heterocycle alkyl, heterocycle connected to R 17 by alkyl, alkoxyalkoxy or halogen;

R 20 and R 21 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, aryl, C 3-10 cycloalkyl, C 4-10 cycloalkenyl, —C(═O)R 12 , or —C(═S)R 12 ;

R 26 is independently selected from hydrogen, C 1-18 alkyl, C 3-10 cycloalkyl, aryl, heterocycle, where each is optionally independently substituted with 1 to 3 of C 1-6 alkyl, C 1-6 alkoxy, halo, CH 2 OH, benzyloxy, and OH;

and pharmaceutically acceptable salts, and stereoisomers thereof.

18. A compound having the general formula:

wherein:

one A is —N═, and the other A is ═CR 26 ;

R 1 is phenyl optionally substituted with 1 or 2 halogens;

X is C 1 -C 3 alkylene, wherein 1 or 2 —CH 2 — groups optionally are independently replaced with —O—, ═O, —OR 27 , —NR 27 , or —N(R 27 ) 2 , where R 27 independently is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl;

R 3 is absent or is selected from hydrogen, phenyl, and an aromatic heterocycle with 5 or 6 ring atoms with either 1, 2 or 3 N, 1 N and 1 O, or 1 or 2 N and 1 S atoms in the ring, where the phenyl or heterocyclic groups are each optionally substituted with 1 or more R 17 ;

R 17 is halogen, C 1-6 halogenated alkyl, or phenyl, wherein the phenyl is optionally substituted with 1 or more halogen, —NR 20 R 21 , C 1-6 alkoxy, C 1-6 haloalkyl, or C 1-6 haloalkyloxy groups;

R 20 and R 21 are independently selected from hydrogen, C 1-18 alkyl, C 2-18 alkenyl, C 2-18 alkynyl, aryl, C 3-10 cycloalkyl, or C 4-10 cycloalkenyl;

R 26 is hydrogen, cyclopentyl, or cyclohexyl;

and pharmaceutically acceptable salts, and stereoisomers thereof.