Antiviral compounds
Novel compounds, methods, and compositions for treating various viral infections are described. In some embodiments the novel compounds of the invention are 3-oxo-phenothiazine derivatives; more specific embodiments include 3-oxo-phenothiazine derivatives having substituents at the 1-, 7-, and 9-positions of the phenothiazine parent ring. In other embodiments, the invention provides compositions and methods for treating viral infections, especially HIV.
1. A compound having the structure:
and its pharmaceutically acceptable salts and hydrates, wherein:
R 9 is selected from the group consisting of: halo, cyano, nitro, amino, carboxyl, formyl, sulfo, sulfinyl, sulfeno, sulfenamoyl, sulfonamino, and optionally substituted loweralkyl, loweralkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkycarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, loweralkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkycarbonyl, cycloheteroalkycarbonyl, aralkycarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, loweralkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, loweralkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, diloweralkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, loweralkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, loweralkylsulfonyldioxy, arylsulfonyldioxy, heteroarylsulfonyldioxy, loweralkylsulfo, arylsulfo, heteroarylsulfo, cycloalkylsulfo, loweralkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, cycloalkylsulfinyl, loweralkylsulfeno, arylsulfeno, heteroarylsulfeno, cycloalkylsulfeno, loweralkylsulfoamino, arylsulfoamino, heteroarylsulfoamino, cycloalkylsulfoamino, sulfonaloweralkylcarbonylsulfenamoyl, arylcarbonylsulfenamoyl, heteroarylcarbonylsulfenamoyl, cycloalkylcarbonylsulfenamoyl, cycloheteroalkylcarbonylsulfenamoyl, aralkylcarbonylsulfenamoyl, heteroaralkylcarbonylsulfenamoyl, (cycloalkyl)alkylcarbonylsulfenamoyl, (cycloheteroalkyl)alkylcarbonylsulfenamoyl, diloweralkylsulfenamoyl, arylsulfenamoyl, diarylsulfenamoyl, aralkylsulfenamoyl, diaralkylsulfenamoyl, heteroarylsulfenamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfenamoyl, diheteroaralkylsulfenamoyl, loweralkylcarbonylsulfinamoyl, arylcarbonylsulfinamoyl, heteroarylcarbonylsulfinamoyl, cycloalkylcarbonylsulfinamoyl, cycloheteroalkylcarbonylsulfinamoyl, aralkylcarbonylsulfinamoyl, heteroaralkylcarbonylsulfinamoyl, (cycloalkyl)alkylcarbonylsulfinamoyl, (cycloheteroalkyl)alkylcarbonylsulfinamoyl, diloweralkylsulfinamoyl, arylsulfinamoyl, diarylsulfinamoyl, aralkylsulfinamoyl, diaralkylsulfinamoyl, heteroarylsulfinamoyl, diheteroarylsulfinamoyl, heteroaralkylsulfinamoyl, diheteroaralkylsulfinamoyl, loweralkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R 1 , R 2 , R 4 , R 5 , and R 8 are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, amino, carboxyl, formyl, sulfo, sulfinyl, sulfeno, sulfenamoyl, sulfonamino, and optionally substituted loweralkyl, loweralkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkycarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, loweralkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkycarbonyl, cycloheteroalkycarbonyl, aralkycarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, loweralkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, loweralkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, diloweralkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, loweralkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, loweralkylsulfonyldioxy, arylsulfonyldioxy, heteroarylsulfonyldioxy, loweralkylsulfo, arylsulfo, heteroarylsulfo, cycloalkylsulfo, loweralkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, cycloalkylsulfinyl, loweralkylsulfeno, arylsulfeno, heteroarylsulfeno, cycloalkylsulfeno, loweralkylsulfoamino, arylsulfoamino, heteroarylsulfoamino, cycloalkylsulfoamino, sulfonaloweralkylcarbonylsulfenamoyl, arylcarbonylsulfenamoyl, heteroarylcarbonylsulfenamoyl, cycloalkylcarbonylsulfenamoyl, cycloheteroalkylcarbonylsulfenamoyl, aralkylcarbonylsulfenamoyl, heteroaralkylcarbonylsulfenamoyl, (cycloalkyl)alkylcarbonylsulfenamoyl, (cycloheteroalkyl)alkylcarbonylsulfenamoyl, diloweralkylsulfenamoyl, arylsulfenamoyl, diarylsulfenamoyl, aralkylsulfenamoyl, diaralkylsulfenamoyl, heteroarylsulfenamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfenamoyl, diheteroaralkylsulfenamoyl, loweralkylcarbonylsulfinamoyl, arylcarbonylsulfinamoyl, heteroarylcarbonylsulfinamoyl, cycloalkylcarbonylsulfinamoyl, cycloheteroalkylcarbonylsulfinamoyl, aralkylcarbonylsulfinamoyl, heteroaralkylcarbonylsulfinamoyl, (cycloalkyl)alkylcarbonylsulfinamoyl, (cycloheteroalkyl)alkylcarbonylsulfinamoyl, diloweralkylsulfinamoyl, arylsulfinamoyl, diarylsulfinamoyl, aralkylsulfinamoyl, diaralkylsulfinamoyl, heteroarylsulfenamoyl, diheteroarylsulfinamoyl, heteroaralkylsulfinamoyl, diheteroaralkylsulfinamoyl, loweralkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R 3 is selected from the group consisting of: halo, oxo, imino, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl; and
R 6 and R 7 are selected independently from the group consisting of: hydrogen and optionally substituted loweralkyl, loweralkyloxyloweralkyl, aminoloweralkyl, loweralkylaminoloweralkyl, diloweralkylaminoloweralkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, arylcarbonyl, alkylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, and heteroaralkylcarbonyl; in addition, R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted 4-, 5-, 6-, or 7-membered ring
wherein said optionally substituted is with a group which is hydrooxyl, nitro, amino, imino, cyano, halo, amidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, lower alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, lower alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, aminoalkyl, or cyanoalkyl.
2. A compound of claim 1 , wherein R 3 is oxo.
3. A compound of claim 2 , wherein R 6 and R 7 forms an optionally substituted pyrrolidinyl ring with the nitrogen atom to which they are attached.
4. A compound of claim 3 , wherein R 6 and R 7 , together with the nitrogen atom to which they are attached, is optionally substituted pyrrolidin-1-yl.
5. A compound of claim 4 , wherein at least one of R 1 and R 9 is selected from the group consisting of: halo, optionally substituted loweralkyloxy, and optionally substituted loweralkyl.
6. A compound of claim 5 , wherein at least one of R 1 and R 9 is halo.
7. A compound of claim 6 , wherein both R 1 and R 9 are halo.
8. A compound of claim 7 , wherein R 1 and R 9 are selected from the group consisting of: chloro and fluoro.
9. A compound of claim 8 , wherein R 1 and R 9 are both chloro or both fluoro.
10. A compound of claim 5 , wherein at least one of R 1 and R 9 is loweralkyloxy.
11. A compound of claim 10 , wherein both R 1 and R 9 are methoxy.
12. A compound of claim 2 , wherein R 6 and R 7 , together with the nitrogen atom to which they are attached, is optionally substituted piperazinyl.
13. A compound of claim 12 , wherein R 6 and R 7 , together with the nitrogen atom to which they are attached, is optionally substituted piperazin-1-yl.
14. A compound of claim 13 , wherein both R 1 and R 9 are selected from the group consisting of halo and optionally substituted loweralkyl.
15. A compound of claim 14 , wherein at least one of R 1 and R 9 is halo.
16. A compound of claim 15 , wherein R 1 and R 9 are both chloro or both fluoro.
17. A compound of claim 14 , wherein at least one of R 1 and R 9 is loweralkyl.
18. A compound of claim 17 , wherein at least one of R 1 and R 9 is methyl.
19. A method for treating a viral disease in a mammal afflicted with such disease, wherein said viral disease is selected from the group consisting of HCV, HIV, influenza, Ebola virus, Marburg virus, Dengue virus, Venezuelean equine encephalitis, Chikungunya virus, and West Nile virus, Easter Equine Encephalitis, Western Equine Encephalitis, Monkey Pox, Corona Virus, Respiratory Syncytial Virus, Adenovirus, Human Rhinovirus, and Herpes Simplex Virus, comprising administering to such mammal a therapeutically effective amount of the compound having the structure:
and its pharmaceutically acceptable salts and hydrates, wherein:
R 1 , R 2 , R 4 , R 5 , R 8 , and R 9 are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, amino, carboxyl, formyl, sulfo, sulfinyl, sulfeno, sulfenamoyl, sulfonamino, and optionally substituted loweralkyl, loweralkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkycarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, loweralkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkycarbonyl, cycloheteroalkycarbonyl, aralkycarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, loweralkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, loweralkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, diloweralkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, loweralkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, loweralkylsulfonyldioxy, arylsulfonyldioxy, heteroarylsulfonyldioxy, loweralkylsulfo, arylsulfo, heteroarylsulfo, cycloalkylsulfo, loweralkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, cycloalkylsulfinyl, loweralkylsulfeno, arylsulfeno, heteroarylsulfeno, cycloalkylsulfeno, loweralkylsulfoamino, arylsulfoamino, heteroarylsulfoamino, cycloalkylsulfoamino, sulfonaloweralkylcarbonylsulfenamoyl, arylcarbonylsulfenamoyl, heteroarylcarbonylsulfenamoyl, cycloalkylcarbonylsulfenamoyl, cycloheteroalkylcarbonylsulfenamoyl, aralkylcarbonylsulfenamoyl, heteroaralkylcarbonylsulfenamoyl, (cycloalkyl)alkylcarbonylsulfenamoyl, (cycloheteroalkyl)alkylcarbonylsulfenamoyl, diloweralkylsulfenamoyl, arylsulfenamoyl, diarylsulfenamoyl, aralkylsulfenamoyl, diaralkylsulfenamoyl, heteroarylsulfenamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfenamoyl, diheteroaralkylsulfenamoyl, loweralkylcarbonylsulfinamoyl, arylcarbonylsulfinamoyl, heteroarylcarbonylsulfinamoyl, cycloalkylcarbonylsulfinarnoyl, cycloheteroalkylcarbonylsulfinamoyl, aralkylcarbonylsulfinamoyl, heteroaralkylcarbonylsulfinamoyl, (cycloalkyl)alkylcarbonylsulfinamoyl, (cycloheteroalkyl)alkylcarbonylsulfinamoyl, diloweralkylsulfinamoyl, arylsulfinamoyl, diarylsulfinamoyl, aralkylsulfinamoyl, diaralkylsulfenamoyl, heteroarylsulfinamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfinamoyl, diheteroaralkylsulfenamoyl, loweralkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R 3 is selected from the group consisting of: halo, oxo, imino, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl; and
R 6 and R 7 are selected independently from the group consisting of: hydrogen and optionally substituted loweralkyl, loweralkyloxyloweralkyl, aminoloweralkyl, loweralkylaminoloweralkyl, diloweralkylaminoloweralkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, arylcarbonyl, alkylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, and heteroaralkylcarbonyl; in addition, R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted 4-, 5-, 6-, or 7-membered ring
wherein said optionally substituted is with a group which is hydrooxyl, nitro, amino, imino, cyano, halo, amidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, lower alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, lower alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, aminoalkyl, or cyanoalkyl.
20. A compound of claim 2 , wherein R 6 and R 7 are optionally substituted loweralkyl, alkyloxyalkyl, alkylaminoalkyl, and dialkylaminoalkyl.
21. A compound of claim 2 , wherein R 6 and R 7 are optionally substituted lower alkyl or optionally substituted loweralkyloxyloweralkyl.
22. A compound of claim 2 , wherein R 6 and R 7 are optionally substituted methyl, ethyl, or propyl.
23. A compound of claim 2 , wherein R 6 and R 7 are optionally substituted methyl.
24. A compound of claim 1 , wherein R 6 and R 7 , together with the nitrogen atom to which each is attached, form an optionally substituted 4-, 5-, 6-, or 7-membered ring, and the ring is an optionally substituted pyrrolidinyl, piperidyl, morpholinyl, piperazinyl, azetidinyl, quinuclidinyl, or azepanyl.
25. A compound of claim 1 , which is 7-(1,4-diazepan-1-yl)-1,9-dimethyl-phenothiazin-3-one.
26. A compound of claim 1 , which is 7-(dimethylamino)-1,9-dimethyl-phenothiazin-3-one, 1,9-dimethyl-7-(4-methylpiperazin-1-yl)phenothiazin-3-one, 7-[bis(2-methoxyethyl)amino]-1,9-dimethylphenothiazin-3-one, 1,9-dimethyl-7-morpholino-phenothiazin-3-one, tert-butyl 4-(1,9-dimethyl-7-oxo-phenothizin-3-yl)piperazine-1-carboxylate, 1,9-dimethyl-7-piperazin-1-yl-phenothiazin-3-one, 1,9-dimethyl-7-pyrrolidin-1-yl-phenothiazin-3-one, tert-butyl 4-(1,9-dimethyl-7-oxo-phenothiazin-3-yl)-1,4-diazepane-1-carboxylate, 7-(azepan-1-yl)-1,9-dimethyl-phenothiazin-3-one, 7-(azetidin-1-yl)-1,9-dimethyl-phenothiazin-3-one, 7-(4-isopropylpiperazin-1-yl)-1,9-dimethylphenothiazin-3-one, 1,9-dimethyl-7-(4-methylsulfonylpiperazin-1-yl)phenothiazin-3-one, 1-(1,9-dimethyl-7-oxo-phenothiazin-3-yl)piperidine-4-carboxamide, 1,9-dimethyl-7-[4-(trifluoromethylsulfonyl)piperazin-1-yl]phenothiazin-3-one, 7-(4-isopropylsulfonylpiperazin-1-yl)-1,9-dimethyl-phenothiazin-3-one, 7-(4,4-difluoro-1-piperidyl)-1,9-dimethyl-phenothiazin-3-one, 1-(1,9-dimethyl-7-oxo-phenothiazin-3-yl)piperidine-4-carboxamidine, or 7-(azepan-1-yl)-1,9-diethyl-phenothiazin-3-one.
27. A compound of claim 1 , which is 1,9-dichloro-7-pyrrolidin-1-yl-phenothiazin-3-one, 1,9-dichloro-7-(dimethylamino)phenothiazin-3-one, N-tert-butyl-4-(1,9-dichloro-7-oxo-phenothiazin-3-yl)piperazine-1-carboxamide, 7-[bis(2-methoxyethyl)amino]-1,9-dichlorophenothiazin-3-one, 4-(1,9-dichloro-7-oxo-phenothiazin-3-yl)-N,N-dimethyl-piperazine-1-sulfonamide, 1,9-dichloro-7-[4-(trifluoromethylsulfonyl)piperazin-1-yl]phenothiazin-3-one, tert-butyl 4-(1,9-dichloro-7-oxo-phenothiazin-3-yl)piperazine-1-carboxylate, or 1,9-difluoro-7-pyrrolidin-1-yl-phenothiazin-3-one.
28. A compound of claim 1 , which is 1,9-dimethoxy-7-(4-methylpiperazin-1-yl)phenothiazin-3-one or 1,9-dimethoxy-7-pyrrolidin-1-yl-phenothiazin-3-one.
29. A compound of claim 1 , which is 7-(dimethylamino)-1-fluoro-phenothiazin-3-one, 7-(dimethylamino)-1-(trifluoromethyl)phenothiazin-3-one, 7-[bis(2-methoxyethyl)amino]-3-oxo-phenothiazine-1-carbonitrile, or 1-tert-butyl-7-pyrrolidin-1-yl-phenothiazin-3-one.
30. A method of claim 19 , wherein said compound has the structure:
and its pharmaceutically acceptable salts and hydrates, wherein:
R 9 is selected from the group consisting of: halo, cyano, nitro, amino, carboxyl, formyl, sulfo, sulfinyl, sulfeno, sulfenamoyl, sulfonamino, and optionally substituted loweralkyl, loweralkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkycarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, loweralkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkycarbonyl, cycloheteroalkycarbonyl, aralkycarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, loweralkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, loweralkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, diloweralkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, loweralkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, loweralkylsulfonyldioxy, arylsulfonyldioxy, heteroarylsulfonyldioxy, loweralkylsulfo, arylsulfo, heteroarylsulfo, cycloalkylsulfo, loweralkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, cycloalkylsulfinyl, loweralkylsulfeno, arylsulfeno, heteroarylsulfeno, cycloalkylsulfeno, loweralkylsulfoamino, arylsulfoamino, heteroarylsulfoamino, cycloalkylsulfoamino, sulfonaloweralkylcarbonylsulfenamoyl, arylcarbonylsulfenamoyl, heteroarylcarbonylsulfenamoyl, cycloalkylcarbonylsulfenamoyl, cycloheteroalkylcarbonylsulfenamoyl, aralkylcarbonylsulfenamoyl, heteroaralkylcarbonylsulfenamoyl, (cycloalkyl)alkylcarbonylsulfenamoyl, (cycloheteroalkyl)alkylcarbonylsulfenamoyl, diloweralkylsulfenamoyl, arylsulfenamoyl, diarylsulfenamoyl, aralkylsulfenamoyl, diaralkylsulfenamoyl, heteroarylsulfenamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfenamoyl, diheteroaralkylsulfenamoyl, loweralkylcarbonylsulfinamoyl, arylcarbonylsulfinamoyl, heteroarylcarbonylsulfinamoyl, cycloalkylcarbonylsulfinamoyl, cycloheteroalkylcarbonylsulfinamoyl, aralkylcarbonylsulfinamoyl, heteroaralkylcarbonylsulfinamoyl, (cycloalkyl)alkylcarbonylsulfinamoyl, (cycloheteroalkyl)alkylcarbonylsulfinamoyl, diloweralkylsulfinamoyl, arylsulfinamoyl, diarylsulfinamoyl, aralkylsulfinamoyl, diaralkylsulfinamoyl, heteroarylsulfinamoyl, diheteroarylsulfinamoyl, heteroaralkylsulfinamoyl, diheteroaralkylsulfinamoyl, loweralkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R 1 , R 2 , R 4 , R 5 , and R 8 are selected independently from the group consisting of: hydrogen, halo, cyano, nitro, amino, carboxyl, formyl, sulfo, sulfinyl, sulfeno, sulfenamoyl, sulfonamino, and optionally substituted loweralkyl, loweralkylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, cycloalkylcarbonyloxy, cycloheteroalkylcarbonyloxy, aralkycarbonyloxy, heteroaralkylcarbonyloxy, (cycloalkyl)alkylcarbonyloxy, (cycloheteroalkyl)alkylcarbonyloxy, loweralkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, cycloalkycarbonyl, cycloheteroalkycarbonyl, aralkycarbonyl, heteroaralkylcarbonyl, (cycloalkyl)alkylcarbonyl, (cycloheteroalkyl)alkylcarbonyl, loweralkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, heteroarylaminocarbonyl, heteroaralkylaminocarbonyl, loweralkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, cycloalkylcarbonylamino, cycloheteroalkylcarbonylamino, aralkylcarbonylamino, heteroaralkylcarbonylamino, (cycloalkyl)alkylcarbonylamino, (cycloheteroalkyl)alkylcarbonylamino, diloweralkylamino, arylamino, diarylamino, aralkylamino, diaralkylamino, heteroarylamino, diheteroarylamino, heteroaralkylamino, diheteroaralkylamino, loweralkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, cycloalkylsulfonyl, loweralkylsulfonyldioxy, arylsulfonyldioxy, heteroarylsulfonyldioxy, loweralkylsulfo, arylsulfo, heteroarylsulfo, cycloalkylsulfo, loweralkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, cycloalkylsulfinyl, loweralkylsulfeno, arylsulfeno, heteroarylsulfeno, cycloalkylsulfeno, loweralkylsulfoamino, arylsulfoamino, heteroarylsulfoamino, cycloalkylsulfoamino, sulfonaloweralkylcarbonylsulfenamoyl, arylcarbonylsulfenamoyl, heteroarylcarbonylsulfenamoyl, cycloalkylcarbonylsulfenamoyl, cycloheteroalkylcarbonylsulfenamoyl, aralkylcarbonylsulfenamoyl, heteroaralkylcarbonylsulfenamoyl, (cycloalkyl)alkylcarbonylsulfenamoyl, (cycloheteroalkyl)alkylcarbonylsulfenamoyl, diloweralkylsulfenamoyl, arylsulfenamoyl, diarylsulfenamoyl, aralkylsulfenamoyl, diaralkylsulfenamoyl, heteroarylsulfenamoyl, diheteroarylsulfenamoyl, heteroaralkylsulfenamoyl, diheteroaralkylsulfenamoyl, loweralkylcarbonylsulfinamoyl, arylcarbonylsulfinamoyl, heteroarylcarbonylsulfinamoyl, cycloalkylcarbonylsulfinamoyl, cycloheteroalkylcarbonylsulfinamoyl, aralkylcarbonylsulfinamoyl, heteroaralkylcarbonylsulfinamoyl, (cycloalkyl)alkylcarbonylsulfinamoyl, (cycloheteroalkyl)alkylcarbonylsulfinamoyl, diloweralkylsulfinamoyl, arylsulfinamoyl, diarylsulfinamoyl, aralkylsulfinamoyl, diaralkylsulfinamoyl, heteroarylsulfinamoyl, diheteroarylsulfinamoyl, heteroaralkylsulfinamoyl, diheteroaralkylsulfinamoyl, loweralkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, cycloalkyloxycarbonyl, cycloheteroalkyloxycarbonyl, aralyoxycarbonyloxloxycarbonyl, heteroaralkyloxycarbonyl, (cycloalkyl)alkyloxycarbonyl, (cycloheteroalkyl)alkyloxycarbonyl, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl;
R 3 is selected from the group consisting of: halo, oxo, imino, iminoloweralkyl, iminocycloalkyl, iminocycloheteroalkyl, iminoaralkyl, iminoheteroaralkyl, (cycloalkyl)iminoalkyl, and (cycloheteroalkyl)iminoalkyl; and
R 6 and R 7 are selected independently from the group consisting of: hydrogen and optionally substituted loweralkyl, loweralkyloxyloweralkyl, aminoloweralkyl, loweralkylaminoloweralkyl, diloweralkylaminoloweralkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, arylcarbonyl, alkylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, and heteroaralkylcarbonyl; in addition, R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted 4-, 5-, 6-, or 7-membered ring
wherein said optionally substituted is with a group which is hydrooxyl, nitro, amino, imino, cyano, halo, amidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, lower alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, lower alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, aminoalkyl, or cyanoalkyl.
31. A method of claim 19 , wherein said viral disease is selected from the group consisting of wherein said viral disease is selected from the group consisting of HCV, HIV, influenza, Ebola virus, Marburg virus, Dengue virus, Venezuelean equine encephalitis, Chikungunya virus, and West Nile virus.
32. A method of claim 19 , wherein said viral disease is HIV.
33. A method of claim 19 , wherein said viral disease is influenza.
34. A compound of claim 1 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloheteroalkyl ring.
35. A compound of claim 1 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloalkylamino ring.
36. A compound of claim 1 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloheteroalkylamino ring.
37. A compound of claim 1 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted pyrrolidinyl, piperidyl, morpholinyl, piperazinyl, azetidinyl, quinuclidinyl, or azepanyl.
38. A method of claim 19 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloheteroalkyl ring.
39. A method of claim 19 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloalkylamino ring.
40. A method of claim 19 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted cycloheteroalkylamino ring.
41. A method of claim 19 , wherein said R 6 and R 7 , together with the nitrogen atom to which each is attached, can form an optionally substituted pyrrolidinyl, piperidyl, morpholinyl, piperazinyl, azetidinyl, quinuclidinyl, or azepanyl.