Antiviral compounds

• US 10,358,453 B2
• Filed: 02/24/2016
• Issued: 07/23/2019
• Est. Priority Date: 02/25/2015
• Status: Active Grant

• Current Assignee: Janssen Pharmaceuticals, Inc. (Johnson & Johnson)
• Original Assignee: Alios Biopharma, Inc. (Johnson & Johnson)
• Inventors: Wang, Guangyi, Beigelman, Leonid, Truong, Anh, Stein, Karin Ann
• Primary Examiner(s): Heyer, Dennis
• Assistant Examiner(s): Podgorski, Daniel M
• Application Number:
  US15/052,631
• Publication Number:
  US 20160244460A1
• Time in Patent Office: 1,245 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/4355 the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5355 Non-condensed oxazines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/536 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 221/04 Ortho- or peri-condensed ring systems
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/048 : the oxygen-containing ring being five-membered
• CPC Class Codes: C07D 491/20 : Spiro-condensed systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).

Claims

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^1a can be hydrogen.

3. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^2a and R^2a1 are both hydrogen.

4. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^3a is hydroxy, and R^3a1 is CF₃.

5. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^3a is CF₃, and R^3a1 is NH₂.

6. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein L¹ is

7. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein R^5a1 is an unsubstituted C_1-6 alkyl.

8. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein R^5a2 is hydrogen.

9. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein p is 1.

10. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein p is 2.

11. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein Z² is O.

12. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein Z² is NR^Z.

13. The compound of any one of claim 6, or a pharmaceutically acceptable salt thereof, wherein Z² is CR^Z1R^Z2.

14. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein L¹ is

15. The compound of any one of claim 14, or pharmaceutically acceptable salt thereof, wherein Z³ is O or NR^Z3.

16. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein L¹ is

17. The compound of any one of claim 1, or pharmaceutically acceptable salt thereof, wherein L¹ is

18. The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein L² is

19. The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein L² is

20. The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein L² is

21. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein L¹ is

22. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted phenyl.

23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein A is a phenyl substituted with one or more substituents selected from the group consisting of:

an unsubstituted C_1-4 alkyl, an optionally substituted C_1-4 alkyl, cycloalkyl, hydroxy, an optionally substituted C_1-4 alkoxy, C_1-4 alkoxy, halogen, haloalkyl, an optionally substituted haloalkoxy, nitro, amino, mono-substituted amino, di-substituted amine, —

O-amido, sulfenyl, alkyoxyalkyl, an optionally substituted aryl, an optionally substituted mono-cyclic heteroaryl, an optionally substituted mono-cyclic heterocyclyl, an optionally substituted aryl(C_1-4 alkyl), an optionally substituted monocyclic heteroaryl(C_1-4 alkyl), an optionally substituted monocyclic heterocyclyl(C_1-4 alkyl), hydroxyalkyl and aminoalkyl.

24. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein A is a phenyl substituted with one or more substituents selected from the group consisting of:

methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, t-butoxy, phenoxy, bromo, chloro, fluoro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, cyano, N,N-di-methyl-amine, N,N-di-ethyl-amine, N-methyl-N-ethyl-amine, N-methyl-amino, N-ethyl-amino, amino, N-amido, N-sulfonamido, alkylthio, an optionally substituted phenyl, an optionally substituted imidazole, an optionally substituted morpholinyl, an optionally substituted pyrazole, an optionally substituted pyrrolidinyl, an optionally substituted pyridinyl, an optionally substituted piperidinyl, an optionally substituted piperidinone, an optionally substituted pyrrolidinone, an optionally substituted pyrimidine, an optionally substituted pyrazine, an optionally substituted 1,2,4-oxadiazole, —

(CH₂)_1-4—

OH, —

(CH₂)_1-2—

NH(CH₃), an optionally substituted —

(CH₂)_1-2-imidazole, an optionally substituted —

(CH₂)_1-2-pyrrolidinone, an optionally substituted —

(CH₂)_1-2-imidazolidinone, —

O(CH₂)₂—

NH₂, —

O(CH₂)₂—

NH(CH₃), —

O(CH₂)₂—

N(CH₃)₂, —

O—

(CH₂)_2-4OH, —

O(CH₂)₂OCH₃, an optionally substituted —

O(CH₂)_0-2-cyclopentanone, an optionally substituted —

O(CH₂)_0-2pyrrolidinone, an optionally substituted —

O(CH₂)_0-2-morpholinyl, an optionally substituted —

O(CH₂)_0-2-triazole, an optionally substituted —

O(CH₂)_0-2-imidazole, an optionally substituted —

O(CH₂)_0-2-pyrazole, an optionally substituted —

O(CH₂)_0-2-tetrahydrofuran, an optionally substituted —

O(CH₂)_0-2-pyrrolidinone, an optionally substituted —

O(CH₂)_0-2-tetrazole, an optionally substituted —

O(CH₂)_0-2-tetrazolone, —

NH(CH₂)_1-2OH,

25. The compound of any one of claim 22, or a pharmaceutically acceptable salt thereof, wherein A is a di-substituted phenyl.

26. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted heteroaryl or an optionally substituted heterocyclyl.

27. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted aryl.

28. The compound of any one of claim 27, or a pharmaceutically acceptable salt thereof, wherein Y is substituted with one or more R^B, wherein each R^B is independently selected from the group consisting of:

cyano, halogen, an optionally substituted C_1-4 alkyl, an unsubstituted C_2-4 alkenyl, an unsubstituted C_2-4 alkynyl, an optionally substituted aryl, an optionally substituted 5 or 6 membered heteroaryl, an optionally substituted 5 or 6 membered heterocyclyl, hydroxy, C_1-4 alkoxy, alkoxyalkyl, C_1-4 haloalkyl, haloalkoxy, an unsubstituted acyl, an optionally substituted —

C-carboxy, an optionally substituted —

C-amido, sulfonyl, carbonyl, amino, mono-substituted amine, di-substituted amine and

29. The compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted heteroaryl or an optionally substituted heterocyclyl.

30. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

31. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

32. The compound of claim 1, wherein the compound of Formula (I) is selected from the group consisting of:

33. A pharmaceutical composition comprising an effective amount of a compound of any one of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

34. A method for ameliorating or treating a paramyxovirus infection comprising administering to a subject identified as suffering from the paramyxovirus infection an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

35. The use of claim 34, wherein the paramyxovirus infection is a human respiratory syncytial virus infection, further comprising administering one or more additional anti-viral agents, wherein the one or more additional anti-viral agents is an anti-RSV agent selected from the group consisting of an anti-RSV antibody, a fusion protein inhibitor, an N-protein inhibitor, a RSV polymerase inhibitor, an IMPDH inhibitor, an interferon and another compound that inhibits the RSV virus, or a pharmaceutically acceptable salt of any of the foregoing.

36. The use of claim 35, wherein the one or more additional anti-viral agents is selected from the group consisting of RSV-IGIV, palivizumab, motavizumab, 1-cyclopropyl-3-[[1-(4-hydroxybutyl)benzimidazol-2-yl]methyl]imidazo[4,5-c]pyridin-2-one (BMS-433771), 4,4″

-bis-{4,6-bis-[3-(bis-carbamoylmethyl-sulfamoyl)-phenylamino]-(1,3,5)triazin-2-ylamino}-biphenyl-2,2″

-disulfonic-acid (RFI-641), 4,4′

-Bis[4,6-di[3-aminophenyl-N,N-bis(2-carbamoylethyl)-sulfonilimino]-1,3,5-triazine-2-ylamino]-biphenyl-2,2′

-disulfonic acid, disodium salt (CL387626), 2-[[2-[[1-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]-6-methyl-3-pyridinol (JNJ-2408068), 2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl]amino]methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol (TMC-353121), 5,5′

-bis[1-(((5-amino-1H-tetrazolyl)imino)methyl)]2,2′

,4″

-methylidynetrisphenol (VP-14637, MDT-637), N-(2-hydroxyethyl)-4-methoxy-N-methyl-3-(6-methyl-[1,2,4]triazolo[3,4-a]phthalazin-3-yl)benzenesulfonamide (P13), 2-((2-((1-(2-aminoethyl)piperidin-4-yl)amino)-4-methyl-1H-benzo[d]imidazol-1-yl)methyl)-6-methylpyridin-3-ol (R170591), 1,4-bis(3-methylpyridin-4-yl)-1,4-diazepane (C15), (R)-9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-2,3-dihydro-1H-imidazo[1′

,2′

;

1,2]pyrrolo[3,4-c]pyridin-5(9bH)-one (BTA9981), [2,2-bis(docosyloxy-oxymethyl)propyl-5-acetaoamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium-oxysulfonyl)-D-glycero-D-galacto-2-nonulopyranosid]onate (MBX-300), BTA-C286, N-(2-((S)-2-(5-((S)-3-aminopyrrolidin-1-yl)-6-methylpyrazolo[1,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-4-chlorophenyl)methanesulfonamide (GS-5806), an anti-RSV nanobody, a peptide fusion inhibitor (such as a peptide having the sequence DEFDASISQVNEKINQSLAFIRKSDELL (T-67), a peptide having the sequence FDASISQVNEKINQSLAFIRKSDELLHNVNAGKST (T-118), (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (RSV-604), STP-92, iKT-041, 6-{4-[(biphenyl-2-ylcarbonyl) amino]benzoyl}-N-cyclopropyl-5,6-dihydro-4H-thieno[3,2-d][1]benzazepine-2-carboxamide (YM-53403). N-cyclopropyl-5-(4-(2-(pyrrolidin-1-yl)benzamido)benzoyl)-5,6,7,10-tetrahydrobenzo[b]cyclopenta[d]azepine-9-carboxamide, 6-(4-(2-(2-oxa-7-azaspiro[3.5]nonan-7-yl)nicotinamido)benzoyl)-N-cyclopropyl-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, 4-amino-8-(3-{[2-(3,4-dimethoxyphenyl)ethyl]amino}propyl)-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-1H-imidazo[4,5-h]-isoquinoline-7,9(6H,8H)-dione, AZ27, ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl)tetrahydrofuran-2-yl)-1H-1,2,4-triazole-3-carboximidamide (Taribavirin, viramidine), (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(chloromethyl)-4-fluoro-2-((isobutyryloxy)methyl)tetrahydrofuran-3-yl isobutyrate, (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(chloromethyl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl isobutyrate, ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(chloromethyl)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methyl triphosphate, 4-amino-1-((2R,3R,4R,5R)-5-(chloromethyl)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one, 1,3,4-thiadiazol-2-ylcyanamide (LY253963), tetrahydrofuran-3-yl-3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate (VX-497), (4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid (Mycophenolic acid), 2-morpholin-4-ylethyl-(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate (Mycophenolate Mofetil), a Type 1 interferon, a Type 2 interferon, a Type 3 interferon, a double stranded RNA oligonucleotide, 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-carboxamide (leflumomide), N-(2-chloro-4-methylphenyl)-2-((1-(4-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)thio)propanamide (JMN3-003), an intratracheal formulation of recombinant human CC10 (CG-100), high titer, human immunoglobulin (RI-001), a non-neutralizing mAb against the G protein (mAb 131-2G), ALN-RSV01, ALN-RSV02, Medi-559, Medi-534 and Medi-557, or a pharmaceutically acceptable salt of any of the foregoing.

37. A method for inhibiting replication of a paramyxovirus comprising contacting a cell infected with the paramyxovirus with an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

38. The use of any one of claim 37, wherein the paramyxovirus infection is a human respiratory syncytial virus infection.

39. A compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of:

40. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^1a is hydrogen.

41. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^2a and R^2a1 are both hydrogen.

42. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^3a is hydroxy;

and R^3a1 is CF₃.

43. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein L¹ is

44. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^5a is an unsubstituted C_1-6 alkyl.

45. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^5a is —

(CH₂)_1-4OH.

46. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^6a1 and R^6a2 are each hydrogen.

47. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein R^4a is hydrogen.

48. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein L¹ is

49. The compound of claim 48, or a pharmaceutically acceptable salt thereof, wherein L² is selected from the group consisting of

50. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein A is a di-substituted phenyl;

or wherein A is a phenyl substituted with one or more substituents selected from the group consisting of;

an unsubstituted C_1-4 alkyl, a substituted C_1-4 alkyl, cycloalkyl, hydroxy, a substituted C_1-4 alkoxy, an unsubstituted C_1-4 alkoxy, halogen, haloalkyl, an optionally substituted haloalkoxy, nitro, amino, mono-substituted amine, di-substituted amine, -O-amido, sulfenyl, alkyoxyalkyl, an optionally substituted aryl, an optionally substituted mono-cyclic heteroaryl, an optionally substituted mono-cyclic heterocyclyl, an optionally substituted aryl(C_1-4 alkyl), an optionally substituted monocyclic heteroaryl(C_1-4 alkyl), an optionally substituted monocyclic heterocyclyl(C_1-4 alkyl), hydroxyalkyl and aminoalkyl.

51. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein A is a phenyl substituted with one or more substituents selected from the group consisting of:

methyl, ethyl, propyl, butyl, hydroxy, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, t-butoxy, bromo, chloro, fluoro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, N,N-di-methyl-amine, N,N-di-ethyl-amine, N-methyl-N-ethyl-amine, N-methyl-amine, N-ethyl-amine, amino, an optionally substituted phenyl, an optionally substituted imidazole, an optionally substituted morpholinyl, an optionally substituted pyrazole, an optionally substituted pyrrolidinyl, an optionally substituted pyridinyl, an optionally substituted piperidinyl, an optionally substituted piperidinone, an optionally substituted pyrrolidinone, an optionally substituted pyrimidine, an optionally substituted pyrazine, an optionally substituted 1,2,4-oxadiazole, —

(CH₂)_1-4—

OH, —

(CH₂)_1-2—

NH(CH₃), an optionally substituted —

(CH₂)_1-2-imidazole, an optionally substituted —

(CH₂)_1-2-pyrrolidinone, an optionally substituted —

(CH₂)_1-2-imidazolidinone, —

O(CH₂)₂—

NH₂, —

O(CH₂)₂—

NH(CH₃), —

O(CH₂)₂—

N(CH₃)₂, —

O—

(CH₂)_2-4OH, —

O(CH₂)₂OCH₃, —

NH(CH₂)_1-2OH,

52. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted heteroaryl;

or wherein A is a heteroaryl selected from the group consisting of;

an optionally substituted imidazole, an optionally substituted indole, an optionally substituted thiazole, an optionally substituted furan, an optionally substituted thiophene, an optionally substituted pyrrole, an optionally substituted pyridine, an optionally substituted pyrimidine, an optionally substituted pyrazine, an optionally substituted pyrazole, an optionally substituted quinolone, an optionally substituted imidazole, an optionally substituted oxazole, an optionally substituted isoxazole, an optionally substituted benzoimidazole, an optionally substituted benzooxazole, an optionally substituted benzothiazole and an optionally substituted imidazo[1,2-a]pyrimidine.

53. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein A is an optionally substituted heterocyclyl;

or wherein A is an optionally substituted heterocyclyl selected from the group consisting of;

an optionally substituted

54. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted aryl;

or wherein Y is a mono-substituted phenyl.

55. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein Y is an optionally substituted heteroaryl or heterocyclyl.

56. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

57. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

58. A pharmaceutical composition comprising an effective amount of a compound of claim 39, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.

59. A method for ameliorating or treating a paramyxovirus infection comprising administering to a subject identified as suffering from the paramyxovirus infection an effective amount of a compound of claim 39, or a pharmaceutically acceptable salt thereof.

60. A method for inhibiting replication of a paramyxovirus comprising contacting a cell infected with the paramyxovirus with an effective amount of a compound of claim 39, or a pharmaceutically acceptable salt thereof.

61. The method of claim 60, wherein the paramyxovirus infection is a human respiratory syncytial virus infection.

62. The method of claim 59, wherein the paramyxovirus infection is a human respiratory syncytial virus infection, further comprising administering one or more additional anti-viral agents, wherein the one or more additional anti-viral agents is an anti-RSV agent selected from the group consisting of an anti-RSV antibody, a fusion protein inhibitor, an N-protein inhibitor, a RSV polymerase inhibitor, an IMPDH inhibitor, an interferon and another compound that inhibits the RSV virus, or a pharmaceutically acceptable salt of any of the foregoing.

63. The method of Claim 62, wherein the one or more additional anti-viral agents is selected from the group consisting of RSV-IGIV, palivizumab, motavizumab, 1-cyclopropyl-3-[[1-(4-hydroxybutyl)benzimidazol-2-yl]methyl]imidazo[4,5-c]pyridin-2-one (BMS-433771), 4,4″

-bis-{4,6-bis-[3-(bis-carbamoylmethyl-sulfamoyl)-phenylamino]-(1,3,5)triazin-2-ylamino}-biphenyl-2,2′

-disulfonic-acid (RFI-641), 4,4′

-Bis[4,6-di[3-aminophenyl -N,N-bis(2-carbamoylethyl)-sulfonilimino]-1,3,5-triazine-2-ylamino]-biphenyl-2,2′

-disulfonic acid, disodium salt (CL387626), 2-[[2-[[1-(2-aminoethyl)-4-piperidinyl]amino]-4-methyl-1H-benzimidazol-1-yl]-6-methyl-3-pyridinol (JNJ-2408068), 2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl]amino]methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol (TMC-353121), 5,5′

-bis[1-(((5-amino-1H-tetrazolyl)imino)methyl)]2,2′

,4″

-methylidynetrisphenol (VP-14637, MDT-637), N-(2-hydroxyethyl)-4-methoxy-N-methyl-3-(6-methyl-[1,2,4]triazolo[3,4-a]phthalazin-3 -yl)benzenesulfonamide (P13), 2-((2-((1-(2-aminoethyl)piperidin-4-yl)amino)-4-methyl-1H -benzo[d]imidazol-1-yl)methyl)-6-methylpyridin-3-ol (R170591), 1,4-bis(3-methylpyridin-4-yl)-1,4-diazepane (C15), (R)-9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-2,3-dihydro-1H -imidazo[1′

,2′

;

1,2]pyrrolo[3,4-c]pyridin-5(9bH)-one (BTA9981), [2,2-bis(docosyloxy -oxymethyl)propyl-5-acetaoamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium-oxysulfonyl)-D-glycero-D-galacto-2-nonulopyranosid]onate (MBX-300), BTA-C286, N-(2-((S)-2-(5-((S)-3-aminopyrrolidin-1-yl)-6-methylpyrazolo[1,5-a]pyrimidin-2-yl)piperidine-1-carbonyl)-4-chlorophenyl)methanesulfonamide (GS-5806), an anti-RSV nanobody, a peptide fusion inhibitor (such as a peptide having the sequence DEFDASISQVNEKINQSLAFIRKSDELL (T-67), a peptide having the sequence FDASISQVNEKINQSLAFIRKSDELLHNVNAGKST (T-118), (S)-1-(2-fluoropheny1)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)urea (RSV-604), STP-92, iKT-041, 6-{4-[(biphenyl-2-ylcarbonyl) amino]benzoyl }-N-cyclopropyl-5,6-dihydro-4H-thieno[3,2-d][1]benzazepine-2-carboxamide (YM-53403). N-cyclopropyl-5-(4-(2-(pyrrolidin-1-yl)benzamido)benzoyl)-5,6,7,10-tetrahydrobenzo[b]cyclopenta[d]azepine-9-carboxamide, 6-(4-(2-(2-oxa-7-azaspiro[3,5]nonan-7-yl)nicotinamido)benzoyl)-N-cyclopropyl-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide, 4-amino-8-(3-{[2-(3,4-dimethoxyphenyl)ethyl]amino}propyl)-6,6-dimethyl-2-(4-methyl-3-nitrophenyl)-1H-imidazo[4,5-h]-isoquinoline-7,9(6H,8H)-dione, AZ27, ribavirin, 5-ethynyl-1-beta-D -ribofuranosylimidazole-4-carboxamide (EICAR), 4-hydroxy-3-beta-D-ribofuranosylpyrazole-5-carboxamide (pyrazofurin), 1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran -2-yl)-1H-1,2,4-triazole-3-carboximidamide (taribavirin, viramidine), (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin -1(2H)-yl)-2-(chloromethyl)-4-fluoro-2-((isobutyryloxy)methyl)tetrahydrofuran-3-yl isobutyrate, (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin -1(2H)-yl)-2-(chloromethyl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl isobutyrate, ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(chloromethyl)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methyl triphosphate, 4-amino-1-((2R,3R,4R,5R)-5-(chloromethyl)-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one, 1,3,4-thiadiazol-2-ylcyanamide (LY253963), tetrahydrofuran-3-yl-3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)benzylcarbamate (VX-497), (4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid (Mycophenolic acid), 2-morpholin-4-ylethyl -(E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate (Mycophenolate Mofetil), a Type 1 interferon, a Type 2 interferon, a Type 3 interferon, a double stranded RNA oligonucleotide, 5-methyl-N-[4-(trifluoromethyl) phenyl]-isoxazole-4-carboxamide (leflumomide), N-(2-chloro-4-methylphenyl)-2-((1-(4-methoxyphenyl)-1H -benzo[d]imidazol-2-yl)thio)propanamide (JMN3-003), an intratracheal formulation of recombinant human CC0O (CG-100), high titer, human immunoglobulin (RI-001), a non-neutralizing mAb against the G protein (mAb 131-2G), ALN-RSV01, ALN-RSV02, Medi-559, Medi-534 and Medi-557, or a pharmaceutically acceptable salt of any of the foregoing.