PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: 2. The method of wherein the Pneumovirinae virus infection is caused by human respiratory syncytial virus.3. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent selected from ribavirin claim 1 , palivizumab claim 1 , motavizumab claim 1 , RSV-IGIV claim 1 , MEDI-557 claim 1 , A-60444 claim 1 , MDT-637 claim 1 , BMS-433771 claim 1 , ALN-RSV0 and ALX-0171 claim 1 , or mixtures thereof.4. The method of wherein the therapeutically effective amount is a daily dose of from 1 mg to 1 claim 1 ,000 mg administered in a single dose or multiple doses.5. The method of wherein the therapeutically effective amount is administered orally.6. The method of wherein the therapeutically effective amount is administered in an aqueous solution or suspension.7. The method of wherein the therapeutically effective amount is a daily dose of from 5 mg to 500 mg administered in a single dose or multiple doses.8. The method of wherein the therapeutically effective amount is administered orally.9. The method of wherein the therapeutically effective amount is administered in an aqueous solution or suspension.10. The method of wherein the pharmaceutically acceptable salt is a trifluoroacetic acid salt. This patent application is a continuation of U.S. patent application Ser. No. 13/905,410, filed May 30, 2013, which is a continuation of U.S. patent application Ser. No. 13/167,618, filed Jun. 23, 2011 (now U.S. Pat. No. 8,486,938), which claims the benefit of U.S. Provisional Patent Application No. 61/358,122, filed Jun. 24, 2010. These applications are incorporated herein by reference in their entireties.The invention relates generally to methods and compounds for treating Pneumovirinae virus infections, particularly methods and nucleosides for treating respiratory syncytial virus infections.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that ...

Macrocyclic inhibitors of flaviviridae viruses

... and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Synthesis of an antiviral compound

The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.

Compounds and methods for antiviral treatment

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: 138-. (canceled)41. A method of treating a Pneumovirinae virus infection in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt or ester thereof.42. A method of treating a Pneumovirinae virus infection in a mammal in need thereof comprising administering to the mammal a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt or ester thereof.43. The method of wherein the Pneumovirinae virus infection is caused by a respiratory syncytial virus.44. The method of wherein the Pneumovirinae virus infection is caused by a respiratory syncytial virus.45. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of ribavirin claim 41 , palivizumab claim 41 , motavizumab claim 41 , RSV-IGIV MEDI-557 claim 41 , A-60444 claim 41 , MDT-637 claim 41 , BMS-433771 claim 41 , ALN-RSV0 and ALX-0171 or mixtures thereof.46. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of ribavirin claim 42 , palivizumab claim 42 , motavizumab claim 42 , RSV-IGIV MEDI-557 claim 42 , A-60444 claim 42 , MDT-637 claim 42 , BMS-433771 claim 42 , ALN-RSV0 and ALX-0171 or mixtures thereof. This patent application claims the benefit of priority of U.S. application Ser. No. 61/358,122, filed Jun. 24, 2010.The invention relates generally to methods and compounds for treating Pneumovirinae virus infections, particularly methods and nucleosides for treating respiratory syncytial virus infections.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The Pneumovirinae sub-family of viruses ...

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 1. (canceled)34-. (canceled)5. The method of claim 2 , wherein Ris selected from the group of CN claim 2 , unsubstituted C-Calkyl claim 2 , C-Calkyl substituted with 1 claim 2 , 2 claim 2 , or 3 halogens selected from F and Cl claim 2 , C-Calkyl substituted with 1 substituent selected from —S—CHand —O—CH claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , unsubstituted C-Ccycloalkyl claim 2 , C-Ccycloalkyl substituted by 1 claim 2 , 2 claim 2 , or 3 substituents selected from F and CH;6. The method of claim 2 , wherein Ris hydrogen.7. The method of claim 2 , wherein Ris F.8. (canceled)9. The method of claim 2 , wherein R claim 2 , R claim 2 , and R are each hydrogen.10. The method of claim 2 , wherein Ris F and Rand Rare each hydrogen.11. The method of claim 2 , wherein Ris CN claim 2 , methyl claim 2 , ethyl claim 2 , propyl claim 2 , vinyl claim 2 , propenyl claim 2 , ethynyl claim 2 , CHF claim 2 , CHF claim 2 , CHCl claim 2 , CHSMe claim 2 , —CHOMe claim 2 , or cyclopropyl.1215-. (canceled)1921-. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/040,349, filed on Aug. 21, 2014, which is hereby incorporated by reference in its entirety.Provided herein are substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds, methods and pharmaceutical formulations for treating Pneumovirinae virus infections, particularly including respiratory syncytial virus infections, and methods and intermediates useful for preparing the compounds.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The ...

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: 138-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/167,618, filed Jun. 23, 2011, which claims the benefit of priority of U.S. Provisional Application No. 61/358,122, filed Jun. 24, 2010. These applications are incorporated herein by reference in their entireties.The invention relates generally to methods and compounds for treating Pneumovirinae virus infections, particularly methods and nucleosides for treating respiratory syncytial virus infections.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The Pneumovirinae sub-family of viruses is a part of the family Paramyxoviridae and includes human respiratory syncytial virus (HRSV). Almost all children will have had an HRSV infection by their second birthday. HRSV is the major cause of lower respiratory tract infections in infancy and childhood with 0.5% to 2% of those infected requiring hospitalization. The elderly and adults with chronic heart, lung disease or those that are immunosuppressed also have a high risk for developing severe HRSV disease (http://www.cdc.gov/rsv/index.html). No vaccine to prevent HRSV infection is currently available. The monoclonal antibody palivizumab is available for immunoprophylaxis, but its use is restricted to infants at high risk, e.g., premature infants or those with either congenital heart or lung disease, and the cost for general use is often prohibitive. In addition, nucleoside analog ribavirin has been approved as the only antiviral agent to treat HRSV infections but has limited efficacy. Therefore, there is a need for anti-Pneumovirinae therapeutics.Certain racemic phenyl(2-(pyrazolo[1,5-a]pyrimidin-2-yl)piperidin-1-yl)methanone compounds are offered for sale by Asinex Corporation (101 N. Chestnet St., Winston-Salem, N.C. 27101) but the utility of these compounds for treating Pneumovirinae ...

PYRROLO[1,2-f][1,2,4]TRIAZINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. 130-. (canceled)35. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt of .36. A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt of .37. A pharmaceutical composition comprising the compound of .38. A pharmaceutical composition comprising the compound of .39. A method of treating a Pneumovirinae virus infection in a human claim 31 , the method comprising administering to the human a therapeutically effective amount of the compound or the pharmaceutically acceptable salt of .40. The method of claim 39 , wherein the Pneumovirinae virus infection in the human is a human respiratory syncytial virus infection.41. A method of treating a Pneumovirinae virus infection in a human claim 32 , the method comprising administering to the human a therapeutically effective amount of the compound or the pharmaceutically acceptable salt of .42. The method of claim 41 , wherein the Pneumovirinae virus infection in the human is a human respiratory syncytial virus infection.43. A method of treating a Pneumovirinae virus infection in a human claim 33 , the method comprising administering to the human a therapeutically effective amount of the compound of .44. The method of claim 43 , wherein the Pneumovirinae virus infection in the human is a human respiratory syncytial virus infection.45. A method of treating a Pneumovirinae virus infection in a human claim 34 , the method comprising administering to the human a therapeutically effective amount of the compound of .46. The method of claim 45 , wherein the Pneumovirinae virus infection in the human is a human ...

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.4. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein said C-Ccarbocyclene is optionally substituted with C-Calkyl or C-Chaloalkyl.5. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein the C-Ccarbocyclene is optionally substituted with methyl claim 1 , ethyl or trifluoromethyl.6. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is cyclopropylene.7. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Cbridged bicyclic carbocyclylene or C-Cfused bicyclic carbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons.8. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is ...

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: 2. The compound of which is a compound of Formula I.3. The compound of wherein each Ris H.5. The compound of which is a compound of Formula VII.6. The compound of wherein Ris H.7. The compound of wherein Ris H claim 1 , halogen or (C-C)alkyl.8. The compound of wherein n is 3 or 4.9. The compound of wherein each Ris independently H or optionally substituted (C-C)alkyl claim 1 , or four Ron adjacent carbon atoms claim 1 , when taken together claim 1 , may form an optionally substituted Caryl ring.11. The compound of wherein A is —(CH)—.12. The compound of wherein X is —CR(NRC(O)OR)— claim 1 , —CR(NRR)— claim 1 , —CR(NRS(O)R)— or X is absent.13. The compound of wherein X is absent.14. The compound of wherein Ris H claim 1 , OR claim 1 , NRR claim 1 , CN claim 1 , (C-C)alkyl claim 1 , C-Caryl claim 1 , C-Cheterocyclyl or (C-C)cycloalkyl claim 1 , wherein any (C-C)alkyl claim 1 , C-Caryl claim 1 , C-Cheterocyclyl or (C-C)cycloalkyl of Ris optionally substituted with one or more oxo claim 1 , halogen claim 1 , hydroxy claim 1 , NH claim 1 , CN claim 1 , N claim 1 , N(R) claim 1 , NHR claim 1 , SH claim 1 , SR claim 1 , S(O)R claim 1 , OR claim 1 , (C-C)alkyl claim 1 , (C-C)haloalkyl claim 1 , —C(O)R claim 1 , —C(O)H claim 1 , —C(═O)OR claim 1 , —C(═O)OH claim 1 , —C(═O)N(R) claim 1 , —C(═O)NHR claim 1 , —C(═O)NH claim 1 , NHS(O)R claim 1 , NRS(O)R claim 1 , NHC(O)R claim 1 , NRC(O)R claim 1 , NHC(O)OR claim 1 , NRC(O)OR claim 1 , NRC(O)NHR claim 1 , NRC(O)N(R) claim 1 , NRC(O)NH claim 1 , NHC(O)NHR claim 1 , NHC(O)N(R) claim 1 , NHC(O)NH claim 1 , ═NH claim 1 , ═NOH claim 1 , ═NOR claim 1 , NRS(O)NHR claim 1 , NRS(O)N(R) claim 1 , NRS(O)NH claim 1 , NHS(O)NHR claim 1 , NHS(O)N(R) claim 1 , NHS(O)NH claim 1 , —OC(═O)R claim 1 , —OP(O)(OH)or R.15. The compound of wherein Ris H or C-Cheterocyclyl claim 1 , wherein any C-Cheterocyclyl of Ris optionally substituted with or more oxo claim 1 , halogen claim 1 , hydroxy ...

Pyrrolo[1,2-f][1,2,4]triazines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds.

2′-chloro aminopyrimidinone and pyrimidine dione nucleosides

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds.

PYRROLO[1,2-f][1,2,4]TRIAZINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. 23-. (canceled)5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris CN claim 1 , —CHCl claim 1 , —CHF claim 1 , —CHF claim 1 , or —CF.6. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris CN claim 5 , —CHCl claim 5 , or —CHF.78-. (canceled)9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris CN.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Chaloalkyl.11. (canceled)12. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris CN or halomethyl.13. (canceled)14. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.18. A compound according to claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris C-Calkyl.19. (canceled)2124-. (canceled)26. A method of treating Pneumovirinae virus infection in a human in need thereof claim 1 , the method comprising administering to the human a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.27. The method of wherein the Pneumovirinae virus infection in the human is a human respiratory syncytial virus infection.28. A pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier or excipient.2930-. (canceled)31. A method of treating Pneumovirinae virus infection in a ...

Methods for treating arenaviridae and coronaviridae virus infections

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

Pyrazolo[1,5-a]pyrimidines for antiviral treatment

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Methods for treating Arenaviridae and Coronaviridae virus infections

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: 2. The method of wherein{'sup': 'e1', 'sub': 1', '6, 'Ris H, C-Calkyl or benzyl; and'}{'sup': 'e2', 'sub': 1', '6, 'Ris H or C-Calkyl.'}5. (canceled)7. (canceled)8. The method of further comprising a pharmaceutically acceptable carrier or excipient.9. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of a corticosteroid claim 1 , an anti-inflammatory signal transduction modulator claim 1 , a β2-adrenoreceptor agonist bronchodilator claim 1 , an anticholinergic claim 1 , a mucolytic agent claim 1 , hypertonic saline and other drugs for treating Filoviridae virus infections; or mixtures thereof.10. (canceled)11. The method of wherein the Filoviridae infection is caused by a Filoviridae virus.12. The method of wherein the Filoviridae infection is caused by an ebolavirus.13. The method of wherein the Filoviridae infection is caused by Bundibugyo ebolavirus claim 1 , Reston ebolavirus claim 1 , Sudan ebolavirus claim 1 , Tai Forest ebolavirus claim 1 , or Zaire ebolavirus.14. The method of wherein the Filoviridae infection is caused by a Marburg virus.15. The method of wherein a Filoviridae polymerase is inhibited.17. (canceled)18. (canceled)19. The method of claim 16 , wherein the Filoviridae infection is caused by a Filoviridae virus.20. The method of claim 16 , wherein the Filoviridae infection is caused by an ebolavirus.21. The method of claim 16 , wherein the Filoviridae infection is caused by a Marburg virus.22. (canceled)23. (canceled)24. (canceled)26. The pharmaceutical composition of claim 25 , wherein{'sup': 'e1', 'Ris H, methyl, or benzyl; and'}{'sup': 'e2', 'Ris H or methyl.'}27. The pharmaceutical composition of claim 25 , wherein{'sup': 'e1 ...

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 2. The compound of claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , butenylene claim 1 , ethylene claim 1 , propylene claim 1 , butylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene claim 1 , pyridylene or pyrimidinylene.3. The compound of claim 1 , wherein Ais isoquinolinylene claim 1 , phenylene or halophenylene.4. The compound of claim 1 , wherein Xis —O— or —NH—; one of Rand Ris H and the other is methyl; Ris iso-propyl; Ris methyl and Ris H or methyl.5. The compound of claim 1 , wherein Ris H or methyl; Ris H; Ris H claim 1 , —OH claim 1 , methoxy claim 1 , trifluoroethoxy; and Ris H.7. The compound of claim 1 , wherein Ais heteroarylene; Ais (C-C)alkylene claim 1 , (C-C)alkenylene claim 1 , (C-C)alkynylene claim 1 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or methyl; and Ris H claim 1 , —OH or (C-C)alkoxy.8. (canceled)9. The compound of claim 1 , wherein Ais arylene;{'sup': 1', '1', '3a', '4a, 'sub': 2', '5', '2', '5', '2', '5', '2', '5', '2', '4', '1', '4', '1', '4', '1', '4, 'and Ais (C-C)alkylene, (C-C)alkenylene, (C-C)alkynylene, —O—(C-C)alkylene, —O—(C-C)alkenylene, wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or methyl; and Ris H, —OH, (C-C)alkoxy or halo(C-C)alkoxy.'}11. The compound of claim 1 , wherein Ais arylene; and Ais pyrazolylene claim 1 , phenylene or pyridylene.12. (canceled)13. The compound of claim 1 , wherein Ais halophenylene; and Ais —O—(C-C)alkylene or —O—(C-C)alkenylene.14. (canceled)17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , isotope claim 1 , stereoisomer claim 1 , mixture of stereoisomers claim 1 , tautomer claim 1 , ester or prodrug thereof and a pharmaceutically acceptable excipient.18. The pharmaceutical composition of claim 17 , further comprising at least one additional ...

SYNTHESIS OF AN ANTIVIRAL COMPOUND

The present disclosure provides processes for the preparation of a compound of formula I: 24-. (canceled)68-. (canceled)1113-. (canceled)1632-. (canceled) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/920,446 filed on Dec. 23, 2013, the entirety of which is incorporated herein by reference.The present disclosure relates generally to the field of organic synthetic methodology for the preparation of Flaviviridae virus inhibitor compounds and their synthetic intermediates.The hepatitis C virus (HCV), a member of the hepacivirus genera within the Flaviviridae family, is the leading cause of chronic liver disease worldwide (Boyer, N. et al. J Hepatol. 2000, 32, 98-112). Consequently, a significant focus of current antiviral research is directed toward the development of improved methods for the treatment of chronic HCV infections in humans (Ciesek, S., von Hahn T., and Manns, M P., Clin. Liver Dis., 2011, 15, 597-609; Soriano, V. et al, J. Antimicrob. Chemother., 2011, 66, 1573-1686; Brody, H., Nature Outlook, 2011, 474, S1-S7; Gordon, C. P., et al., J. Med. Chem. 2005, 48, 1-20; Maradpour, D., et al., Nat. Rev. Micro. 2007, 5, 453-463).Virologic cures of patients with chronic HCV infection are difficult to achieve because of the prodigious amount of daily virus production in chronically infected patients and the high spontaneous mutability of HCV (Neumann, et al., Science 1998, 282, 103-7; Fukimoto, et al., Hepatology, 1996, 24, 1351-4; Domingo, et al., Gene 1985, 40, 1-8; Martell, et al., J. Virol. 1992, 66, 3225-9). HCV treatment is further complicated by the fact that HCV is genetically diverse and expressed as several different genotypes and numerous subtypes. For example, HCV is currently classified into six major genotypes (designated 1-6), many subtypes (designated a, b, c, and so on), and about 100 different strains (numbered 1, 2, 3, and so on).HCV is distributed worldwide with genotypes 1, 2, and 3 ...

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections. 2. The compound of wherein:{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'a) Yis N, NH or CH, Yis C, Yis N or CR, Yis N or C and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '8′', '4', '5', '2′', '1', '2', '3', '4', '5', '2′, 'b) Yis N, NH or CH, Yis N or C, Yis N or CR, Yis N or C, and Yis N or NR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'c) Yis N, NH or CH, Yis N or C, Yis CR, Yis N or C, and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR;'}the dashed bonds ---- are selected from single bonds and double bonds so as to provide an aromatic ring system;{'sup': 4', '4′', '4', '4′', '4', '4′', 'a, 'sub': n', 'n', 'p, 'A is —(CRR)— wherein any one CRR of said —(CRR)— may be optionally replaced with —O—, —S—, —S(O)—, NH or NR;'}n is 3, 4, 5 or 6;each p is 1 or 2;{'sub': 2', '20', '6', '20', '2', '20', '6', '20, 'sup': '6', 'Ar is a C-Cheterocyclyl group or a C-Caryl group, wherein the C-Cheterocyclyl group or the C-Caryl group is optionally substituted with 1 to 5 R;'}{'sup': 13', '14', '14, 'sub': '2', 'X is —C(R)(R)—, —N(CHR)— or —NH—, or X is absent;'}{'sup': 1', '11', '11', '12', '11', '11', '11', '11', '11', '11', '12', '11', 'a', '11', 'a', '11', '11', '11', '12', '11', '11', '11', '12', '11', '11', '11', '11', '12', '11', '11', '11', '12, 'sub': 3', '2', 'p', 'p', 'p', '2', 'p', 'p', '1', '8', '2', '8', '2', '8', '1', '8', '6', '20', '2', '20', '2', '20', '1', '8', ...

METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R is hydrogen.5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein wherein Ris selected from the group of CN claim 1 , unsubstituted C-Calkyl claim 1 , C-Calkyl substituted with 1 claim 1 , 2 claim 1 , or 3 halogens selected from F and Cl claim 1 , C-Calkyl substituted with 1 substituent selected from —S—CHand —O—CH claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , unsubstituted C-Ccycloalkyl claim 1 , C-Ccycloalkyl substituted by 1 claim 1 , 2 claim 1 , or 3 substituents selected from F and CH;6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F.8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both hydrogen.9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , R claim 1 , and R are each hydrogen.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F and Rand R are each hydrogen.11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of H and F; Ris selected from the group of CN claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , vinyl claim 1 , propenyl claim 1 , ethynyl claim 1 , CHF claim 1 , CHF claim 1 , CHCl claim 1 , CHSMe claim 1 , —CHOMe claim 1 , ...

Methods for treating filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Inhibitors of hepatitis C virus

As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

Pyrrolo[1,2-f][1,2,4]triazines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds.

Pyrazolo[1,5-A]pyrimidines for antiviral treatment

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections. 2. The method of wherein:{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'a) Yis N, NH or CH, Yis C, Yis N or CR, Yis N or C and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '4', '5', '2′', '1', '2', '3', '4', '5', '2, 'b) Yis N, NH or CH, Yis N or C, Yis N or CR, Yis N or C, and Yis N or NR, wherein at least two of Y, Y, Y, Y, and Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'c) Yis N, NH or CH, Yis N or C, Yis CR, Yis N or C, and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR;'}the dashed bonds ---- are selected from single bonds and double bonds so as to provide an aromatic ring system;{'sup': 4', '4′', '4', '4′', '4', '4′', 'a, 'sub': n', 'n', 'p, 'A is —(CRR)— wherein any one CRR of said —(CRR)— may be optionally replaced with —O—, —S—, —S(O)—, NH or NR;'}n is 3, 4, 5 or 6;each p is 1 or 2;{'sub': 2', '20', '6', '20', '2', '20', '6', '20, 'sup': '6', 'Ar is a C-Cheterocyclyl group or a C-Caryl group, wherein the C-Cheterocyclyl group or the C-Caryl group is optionally substituted with 1 to 5 R;'}{'sup': 13', '14', '14, 'sub': '2', 'X is —C(R)(R)—, —N(CHR)— or —NH—, or X is absent;'}{'sup': 1', '11', '11', '12', '11', '11', '11', '11', '11', '11', '12', '11', 'a', '11', 'a', '11', '11', '11', '12', '11', '11', '11', '12', '11', '11', '11', '11', '12', '11', '11', '11', '12, 'sub': 3', '2', 'p', 'p', 'p', '2', 'p', '1', '8', '2', '8', '2', '8', '1', '8', '6', '20', '2', '20', '2', '20', '1', '8', '3', '7', '3 ...

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.8. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is C-Calkylene claim 1 , substituted with 1-4 halogens.9. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is Calkylene claim 1 , substituted with two halogens.10. The compound of or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is C-Calkylene.11. The compound of or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is Calkylene.12. The compound of claim 8 , or a stereoisomer claim 8 , or a mixture of stereoisomers claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein the halogens are each fluoro.13. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is t-butyl or C-Ccarbocyclyl.14. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is t-butyl.15. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein E is C-Calkyl optionally substituted with 1-3 halogen atoms.16. The compound of claim 1 , or a stereoisomer claim 1 ...

Inhibitors of hepatitis C virus

Compounds of Formula I are disclosed As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

Pyrrolo[1,2-f][1,2,4]triazines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds.

PYRROLO[1,2-f][1,2,4]TRIAZINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. 13-. (canceled)514-. (canceled)16. A compound according to claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Rand Rare each C-Calkyl.17. A compound according to claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Rand Rare each selected from C-Calkyl.18. A compound according to claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Rand Rare each selected from C-Calkyl.1920-. (canceled)2225-. (canceled)26. A method of treating Pneumovirinae virus infection in a human claim 4 , the method comprising administering to the human a therapeutically effective amount of a compound of claim 4 , or a pharmaceutically acceptable salt thereof.27. The method of wherein the Pneumovirinae virus infection in a human is a human respiratory syncytial virus infection.28. A pharmaceutical formulation comprising a pharmaceutically effective amount of a compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , and a pharmaceutically acceptable carrier or excipient.2930-. (canceled) This application claims the benefit of and priority to U.S. Provisional Application Ser. No. 61/902,544, filed Nov. 11, 2013, the disclosure of which is hereby incorporated by reference in its entirety.Provided herein are substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds, methods and pharmaceutical formulations for treating Pneumovirinae virus infections, particularly including respiratory syncytial virus infections, as well as methods and intermediates useful for preparing the compounds.Pneumovirinae viruses are negative-sense, single-stranded, ...

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R is hydrogen.5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein wherein Ris selected from the group of CN claim 1 , unsubstituted C-Calkyl claim 1 , C-Calkyl substituted with 1 claim 1 , 2 claim 1 , or 3 halogens selected from F and Cl claim 1 , C-Calkyl substituted with 1 substituent selected from —S—CHand —O—CH claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , unsubstituted C-Ccycloalkyl claim 1 , C-Ccycloalkyl substituted by 1 claim 1 , 2 claim 1 , or 3 substituents selected from F and CH;6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F.8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both hydrogen.9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , R claim 1 , and R are each hydrogen.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F and Rand R are each hydrogen.11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of H and F; Ris selected from the group of CN claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , vinyl claim 1 , propenyl claim 1 , ethynyl claim 1 , CHF claim 1 , CHF claim 1 , CHCl claim 1 , CHSMe claim 1 , —CHOMe claim 1 , ...

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: 174-. (canceled)77. The method of claim 75 , further comprising administering a pharmaceutically acceptable carrier or excipient.78. The method of claim 75 , further comprising administering a therapeutically effective amount of at least one other therapeutic agent.79. The method of claim 78 , wherein the at least one other therapeutic agent is selected from the group consisting of a corticosteroid claim 78 , an anti-inflammatory signal transduction modulator claim 78 , a β2-adrenoreceptor agonist bronchodilator claim 78 , an anticholinergic claim 78 , a mucolytic agent claim 78 , hypertonic saline claim 78 , and other drugs for treating a Coronaviridae virus infection; or mixtures thereof.80. The method of claim 75 , wherein the Coronaviridae infection is caused by a Coronaviridae virus selected from the group consisting of SARS claim 75 , MERS claim 75 , 229E claim 75 , NL63 claim 75 , OC43 claim 75 , and HKUL.81. The method of claim 75 , wherein the Coronaviridae infection is caused by a SARS virus.82. The method of claim 75 , wherein the Coronaviridae infection is caused by a MERS virus.83. The method of claim 75 , wherein the compound claim 75 , or a pharmaceutically acceptable salt thereof claim 75 , is administered by oral claim 75 , rectal claim 75 , nasal claim 75 , pulmonary claim 75 , topical claim 75 , vaginal claim 75 , or parenteral administration.84. The method of claim 83 , wherein the compound claim 83 , or a pharmaceutically acceptable salt thereof claim 83 , is administered by parenteral administration.85. The method of claim 75 , wherein the compound claim 75 , or a pharmaceutically acceptable salt thereof claim 75 , is administered by subcutaneous claim 75 , intramuscular claim 75 , intravenous claim 75 , intradermal claim 75 , intrathecal claim 75 , or epidural administration.86. The method of claim ...

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of CN claim 1 , unsubstituted C-Calkyl claim 1 , C-Calkyl substituted with 1 claim 1 , 2 claim 1 , or 3 halogens selected from F and Cl claim 1 , C-Calkyl substituted with 1 substituent selected from —S—CHand —O—CH claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , unsubstituted C-Ccycloalkyl claim 1 , C-Ccycloalkyl substituted by 1 claim 1 , 2 claim 1 , or 3 substituents selected from F and CH;6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F.8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both hydrogen.9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare each hydrogen.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F and Rand Rare each hydrogen.11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of H and F; Ris selected from the group of CN claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , vinyl claim 1 , propenyl claim 1 , ethynyl claim 1 , CHF claim 1 , CHF claim 1 , CHCl claim 1 , CHSMe claim 1 , —CHOMe claim 1 , and ...

PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL AGENTS

The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections. 2. The compound of wherein each Ris H.3. The compound of wherein n is 3.4. The compound of wherein each Ris H.5. The compound of wherein A is —(CH)—.7. The compound of wherein Ar is phenyl claim 1 , pyridyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthyl claim 1 , indazolyl claim 1 , 1 claim 1 ,6-naphthyridyl claim 1 , 2 claim 1 ,3 claim 1 ,-dihydroindanyl claim 1 , quinolyl claim 1 , indolyl claim 1 , 4H-benzo][d][1 claim 1 ,3]dioxanyl claim 1 , pyrazolo[1 claim 1 ,5-a]pyridinyl claim 1 , imidazo[1 claim 1 ,2-a]pyridinyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolyl claim 1 , benzo[d][1 claim 1 ,3]dioxolyl claim 1 , quinoxalyl claim 1 , isoquinolyl claim 1 , naphthyl claim 1 , thiophenyl claim 1 , pyrazolyl claim 1 , 4 claim 1 ,5 claim 1 ,6 claim 1 ,7-tetrahydrobenzothiophenyl or pyrazolo[3 claim 1 ,4 claim 1 ,b]pyridinyl claim 1 , wherein any phenyl claim 1 , pyridyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydronaphthyl claim 1 , indazolyl claim 1 , 1 claim 1 ,6-naphthyridyl claim 1 , 2 claim 1 ,3 claim 1 ,-dihydroindanyl claim 1 , quinolyl claim 1 , indolyl claim 1 , 4H-benzo][d][1 claim 1 ,3]dioxanyl claim 1 , pyrazolo[1 claim 1 ,5-a]pyridinyl claim 1 , imidazo[1 claim 1 ,2-a]pyridinyl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolyl claim 1 , benzo[d][1 claim 1 ,3]dioxolyl claim 1 , quinoxalyl claim 1 , isoquinolyl claim 1 , naphthyl claim 1 , thiophenyl claim 1 , pyrazolyl claim 1 , 4 claim 1 ,5 claim 1 ,6 claim 1 ,7-tetrahydrobenzothiophenyl or pyrazolo[3 claim 1 ,4 claim 1 ,b]pyridinyl of Ar is optionally substituted with 1 to 5 R.8. The compound of wherein each Ris independently OR claim 1 , CN claim 1 , S(O)R claim 1 , ...

Pyrazolo[1,5-A]pyrimidines for antiviral treatment

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

Compounds and methods for antiviral treatment

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 4. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R is hydrogen.5. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein wherein Ris selected from the group of CN claim 1 , unsubstituted C-Calkyl claim 1 , C-Calkyl substituted with 1 claim 1 , 2 claim 1 , or 3 halogens selected from F and Cl claim 1 , C-Calkyl substituted with 1 substituent selected from —S—CHand —O—CH claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , unsubstituted C-Ccycloalkyl claim 1 , C-Ccycloalkyl substituted by 1 claim 1 , 2 claim 1 , or 3 substituents selected from F and CH;6. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F.8. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both hydrogen.9. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , R claim 1 , and R are each hydrogen.10. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris F and Rand R are each hydrogen.11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group of H and F; Ris selected from the group of CN claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , vinyl claim 1 , propenyl claim 1 , ethynyl claim 1 , CHF claim 1 , CHF claim 1 , CHCl claim 1 , CHSMe claim 1 , —CHOMe claim 1 , ...

METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: 2. The method of wherein Ris H.8. The method of further comprising a pharmaceutically acceptable carrier or excipient.9. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of a corticosteroid claim 1 , an anti-inflammatory signal transduction modulator claim 1 , a β2-adrenoreceptor agonist bronchodilator claim 1 , an anticholinergic claim 1 , a mucolytic agent claim 1 , hypertonic saline and other drugs for treating Filoviridae virus infections; or mixtures thereof.10. The method of wherein the at least one other therapeutic agent is ribavirin claim 9 , palivizumab claim 9 , motavizumab claim 9 , RSV-IGIV (RespiGam®) claim 9 , MEDI-557 claim 9 , A-60444 claim 9 , MDT-637 claim 9 , BMS-433771 claim 9 , amiodarone claim 9 , dronedarone claim 9 , verapamil claim 9 , Ebola Convalescent Plasma (ECP) claim 9 , TKM-100201 claim 9 , BCX4430 ((2S claim 9 ,3S claim 9 ,4R claim 9 ,5R)-2-(4-amino-5H-pyrrolo[3 claim 9 ,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine-3 claim 9 ,4-diol) claim 9 , favipiravir (also known as T-705 or Avigan) claim 9 ,T-705 monophosphate claim 9 , T-705 diphosphate claim 9 , T-705 triphosphate claim 9 , FGI-106 (1-N claim 9 ,7-N-bis[3-(dimethylamino)propyl]-3 claim 9 ,9-dimethylquinolino[8 claim 9 ,7-h]quinolone-1 claim 9 ,7-diamine) claim 9 , JK-05 claim 9 , TKM-Ebola claim 9 , ZMapp claim 9 , rNAPc2 claim 9 , VRC-EBOADC076-00-VP claim 9 , OS-2966 claim 9 , MVA-BN filo claim 9 , brincidofovir claim 9 , Vaxart adenovirus vector 5-based ebola vaccine claim 9 , Ad26-ZEBOV claim 9 , FiloVax vaccine claim 9 , GOVX-E301 claim 9 , GOVX-E302 claim 9 , ebola virus entry inhibitors (NPC1 inhibitors) claim 9 , or rVSV-EBOV or mixtures thereof. ...

Synthesis of an antiviral compound

The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.

Pyrazolo[1,5-A]pyrimidines for antiviral treatment

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS

The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

METHODS FOR THE PREPARATION OF RIBOSIDES

Provided are methods of preparing compounds and pharmaceutical compositions for treating Filoviridae virus infections The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: 139.-. (canceled)41. (canceled)43. (canceled)4950.-. (canceled)53. The method of wherein Ris C-Calkyl.54. The method of wherein Ris C-Calkyl.5558.-. (canceled)63. The method of further comprising a pharmaceutically acceptable carrier or excipient.64. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of a corticosteroid claim 40 , an anti-inflammatory signal transduction modulator claim 40 , a β2-adrenoreceptor agonist bronchodilator claim 40 , an anticholinergic claim 40 , a mucolytic agent claim 40 , hypertonic saline and other drugs for treating a Coronaviridae virus infection; or mixtures thereof.65. The method of wherein the Coronaviridae infection is caused by a Coronaviridae virus.66. The method of wherein the Coronaviridae infection is caused by a Coronaviridae virus selected from SARS claim 40 , MERS claim 40 , 229E claim 40 , NL63 claim 40 , OC43 claim 40 , and HKU1.6774.-. (canceled) This patent application is a Continuation of U.S. patent application Ser. No. 15/267,433, filed on Sep. 16, 2016, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 62/219,302, filed Sep. 16, 2015 and U.S. Provisional Application No. 62/239,696, filed Oct. 9, 2015. The foregoing applications are incorporated herein by reference in their entireties.The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 1137P2C_2016-11-28_Sequence_Listing.txt, date recorded: Nov. 29, 2016, size: 1 KB).The invention relates generally to methods and compounds for treating Arenaviridae virus infections, particularly methods and nucleosides and prodrugs thereof for ...

METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: 2. The method of wherein Ris H.8. The method of further comprising a pharmaceutically acceptable carrier or excipient.9. The method of further comprising administering a therapeutically effective amount of at least one other therapeutic agent or composition thereof selected from the group consisting of a corticosteroid claim 1 , an anti-inflammatory signal transduction modulator claim 1 , a β2-adrenoreceptor agonist bronchodilator claim 1 , an anticholinergic claim 1 , a mucolytic agent claim 1 , hypertonic saline and other drugs for treating Filoviridae virus infections; or mixtures thereof.10. The method of wherein the at least one other therapeutic agent is ribavirin claim 9 , palivizumab claim 9 , motavizumab claim 9 , RSV-IGIV (RespiGam®) claim 9 , MEDI-557 claim 9 , A-60444 claim 9 , MDT-637 claim 9 , BMS-433771 claim 9 , amiodarone claim 9 , dronedarone claim 9 , verapamil claim 9 , Ebola Convalescent Plasma (ECP) claim 9 , TKM-100201 claim 9 , BCX4430 ((2S claim 9 ,3S claim 9 ,4R claim 9 ,5R)-2-(4-amino-5H-pyrrolo[3 claim 9 ,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine-3 claim 9 ,4-diol) claim 9 , favipiravir (also known as T-705 or Avigan) claim 9 , T-705 monophosphate claim 9 , T-705 diphosphate claim 9 , T-705 triphosphate claim 9 , FGI-106 (1-N claim 9 ,7-N-bis[3-(dimethylamino)propyl]-3 claim 9 ,9-dimethylquinolino[8 claim 9 ,7-h]quinolone-1 claim 9 ,7-diamine) claim 9 , JK-05 claim 9 , TKM-Ebola claim 9 , ZMapp claim 9 , rNAPc2 claim 9 , VRC-EBOADC076-00-VP claim 9 , OS-2966 claim 9 , MVA-BN filo claim 9 , brincidofovir claim 9 , Vaxart adenovirus vector 5-based ebola vaccine claim 9 , Ad26-ZEBOV claim 9 , FiloVax vaccine claim 9 , GOVX-E301 claim 9 , GOVX-E302 claim 9 , ebola virus entry inhibitors (NPC1 inhibitors) claim 9 , or rVSV-EBOV or mixtures thereof. ...

Inhibitors of hepatitis C virus

As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

Thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-D]pyrimidines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds.

Methods for treating arenaviridae and coronaviridae virus infections

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

PYRAZOLO[1,5-A]PYRIMIDINES FOR ANTIVIRAL TREATMENT

The invention provides compounds of Formula I or Formula II: 138.-. (canceled)41. The process of claim 40 , wherein the reacting step is performed in a solvent comprising triethylamine and methanol.42. The process of claim 40 , comprising heating the reaction to about 75° C.43. The process of claim 40 , wherein the pharmaceutically acceptable salt is trifluoroacetic acid salt.45. The process of wherein the pharmaceutically acceptable salt is trifluoroacetic acid salt.46. The process of wherein the contacting step is performed in a solvent comprising trifluoroacetic acid and dichloromethane.47. The process of wherein the contacting step comprises stirring overnight.50. The process of wherein the contacting step is performed in a solution claim 49 , the solution comprising a solvent and a reagent.55. The process of wherein the reacting step is heated to 100° C. This patent application claims the benefit of priority of U.S. application Ser. No. 61/358122, filed Jun. 24, 2010.The invention relates generally to methods and compounds for treating Pneumovirinae virus infections, particularly methods and nucleosides for treating respiratory syncytial virus infections.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The Pneumovirinae sub-family of viruses is a part of the family Paramyxoviridae and includes human respiratory syncytial virus (HRSV). Almost all children will have had an HRSV infection by their second birthday. HRSV is the major cause of lower respiratory tract infections in infancy and childhood with 0.5% to 2% of those infected requiring hospitalization. The elderly and adults with chronic heart, lung disease or those that are immunosuppressed also have a high risk for developing severe HRSV disease (http://www.cdc.gov/rsv/index.html). No vaccine to prevent HRSV infection is currently available. The monoclonal antibody palivizumab is available for immunoprophylaxis, but ...

METHODS FOR THE PREPARATION OF RIBOSIDES

Provided are methods of preparing compounds and pharmaceutical compositions for treating Filoviridae virus infections The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections. 2. The method of claim 1 , whereinthe coupling agent is a lithium coupling agent or a magnesium coupling agent;{'sub': 3', '3', '3', '2', '2', '2', '3', '2, 'the halo-silane is Cl—Si(CH), or Cl—Si(CH)CHCHSi(CH)—Cl; and'}the hydroxy protecting group is trimethyl silane (TMS), t-butyl dimethyl silane (TBDMS), t-butyl diphenyl silane (TBDPS), methyl-methoxy (MOM), tetrahydropyran (THP), t-butyl, allyl, benzyl, acetyl, pivaloyl, or benzoyl.3. The method of claim 1 , whereinthe coupling agent is PhMgCl and iPrMgCl;the halo-silane is TMS-Cl; andthe hydroxy protecting group is benzyl.6. The method of wherein the deprotonating agent is a lithium coupling agent or a magnesium coupling agent; the silylating agent is a chloro-silane; the coupling agent is a magnesium based coupling agent; and the additive is LaCl-2LiCl claim 5 , YCl claim 5 , CeCl claim 5 , NdCl claim 5 , or LaCl.7. The method of whereinthe deprotonating agent is PhMgCl;the silylating agent is TMSCl;the coupling agent is iPrMgCl;{'sub': 3', '3', '3', '3', '3, 'the additive is LaCl-2LiCl, YCl, CeCl, NdCl, or LaCl; and'}the hydroxy protecting group is benzyl.11. The method of whereinthe cyanating agent is TMSCN;the Lewis Acid is TMSOTf;the Broenstedt acid is TFA;the solvent is DCM; andthe hydroxy protecting group is benzyl.14. The method of whereinthe cyanating agent is TMSCN;the Lewis Acid is TMSOTf;the Broenstedt acid is TFA;the solvent is DCM; andthe hydroxy protecting group is TBS.17. The method of wherein{'sub': '3', 'the Lewis Acid is BCL;'}{'sub': '3', 'the base is EtN;'}the solvent is MeOH; andthe filtering agent is Celite®.20. The method of whereinthe solvent is acetone;the reagent is 2,2-dimethoxypropane; andthe acid is sulfuric acid.23. ...

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed 184.-. (canceled) This application claims the benefit under 35 U.S.C. § 119(e) to U.S. Provisional Application Ser. No. 61/667,806, filed on Jul. 3, 2012, and U.S. Provisional Application Ser. No. 61/798,524, filed on Mar. 15, 2013. The entirety of both applications is incorporated herein by reference.Novel small molecule inhibitors of viral replication are disclosed, compositions containing such compounds, and therapeutic methods comprising the administration of such compounds are also disclosed.The hepatitis C virus (HCV), a member of the hepacivirus genera within the Flaviviridae family, is the leading cause of chronic liver disease worldwide (Boyer, N. et al. 2000, 32, 98-112). Consequently, a significant focus of current antiviral research is directed toward the development of improved methods for the treatment of chronic HCV infections in humans (Ciesek, S., von Hahn T., and Manns, M P., 2011, 15, 597-609, Soriano, V. et al, 2011, 66, 1573-1686; Brody, H., Nature Outlook, 2011, 474, S1-S7; Gordon. C. P., et al., 2005, 48. 1-20; Maradpour, D., et al., 2007, 5, 453-463).Virologic cures of patients with chronic HCV infection are difficult to achieve because of the prodigious amount of daily virus production in chronically infected patients and the high spontaneous mutability of HCV (Neumann, et al., 1998, 282, 103-7; Fukimoto, et al., 1996, 24, 1351-4; Domingo, et al., 1985, 40, 1-8; Martell. et al., 1992, 66, 3225-9). HCV treatment is further complicated by the fact that HCV is genetically diverse and expressed as several different genotypes and numerous subtypes. For example, HCV is currently classified into six major genotypes (designated 1-6), many subtypes (designated a, b, c, and so on), and about 100 different strains (numbered 1, 2, 3, and so on).HCV is distributed worldwide with genotypes 1, 2, and 3 predominate within the United States, Europe, Australia, and East Asia (Japan, Taiwan, Thailand, and China). Genotype 4 ...

Thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-D]pyrimidines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds.

2′-chloro aminopyrimidinone and pyrimidine dione nucleosides

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds.

Compounds and methods for antiviral treatment

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

SYNTHESIS OF AN ANTIVIRAL COMPOUND

The present disclosure provides processes for the preparation of a compound of formula I: 115-. (canceled) This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/920,446 filed on Dec. 23, 2013, the entirety of which is incorporated herein by reference.The present disclosure relates generally to the field of organic synthetic methodology for the preparation of Flaviviridae virus inhibitor compounds and their synthetic intermediates.The hepatitis C virus (HCV), a member of the hepacivirus genera within the Flaviviridae family, is the leading cause of chronic liver disease worldwide (Boyer, N. et al. J Hepatol. 2000, 32, 98-112). Consequently, a significant focus of current antiviral research is directed toward the development of improved methods for the treatment of chronic HCV infections in humans (Ciesek, S., von Hahn T., and Manns, M P., Clin. Liver Dis., 2011, 15, 597-609; Soriano, V. et al, J. Antimicrob. Chemother., 2011, 66, 1573-1686; Brody, H., Nature Outlook, 2011, 474, S1-S7; Gordon, C. P., et al., J. Med. Chem. 2005, 48, 1-20; Maradpour, D., et al., Nat. Rev. Micro. 2007, 5, 453-463).Virologic cures of patients with chronic HCV infection are difficult to achieve because of the prodigious amount of daily virus production in chronically infected patients and the high spontaneous mutability of HCV (Neumann, et al., Science 1998, 282, 103-7; Fukimoto, et al., Hepatology, 1996, 24, 1351-4; Domingo, et al., Gene 1985, 40, 1-8; Martell, et al., J. Virol. 1992, 66, 3225-9). HCV treatment is further complicated by the fact that HCV is genetically diverse and expressed as several different genotypes and numerous subtypes. For example, HCV is currently classified into six major genotypes (designated 1-6), many subtypes (designated a, b, c, and so on), and about 100 different strains (numbered 1, 2, 3, and so on).HCV is distributed worldwide with genotypes 1, 2, and 3 predominate within the United States, Europe, Australia ...

Inhibitors of hepatitis C virus

Compounds of Formula I are disclosed As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed.

METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL AGENTS

The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections.

THIENO[3,2-d]PYRIMIDINE, FURO[3,2-d]PYRIMIDINE, AND PYRROLO[3,2-D]PYRIMIDINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds. 15-. (canceled)717-. (canceled)21. A compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris F or OH.2328-. (canceled)31. A pharmaceutical composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , and a pharmaceutically acceptable carrier or excipient.32. A pharmaceutical composition comprising a compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , and a pharmaceutically acceptable carrier or excipient.33. A pharmaceutical composition comprising a compound of claim 29 , or a pharmaceutically acceptable salt thereof claim 29 , and a pharmaceutically acceptable carrier or excipient.34. A pharmaceutical composition comprising a compound of claim 30 , or a pharmaceutically acceptable salt thereof claim 30 , and a pharmaceutically acceptable carrier or excipient.35. A method of treating Pneumovirinae virus infection in a human in need thereof claim 6 , the method comprising administering to the human in need thereof a therapeutically effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof.36. The method of claim 35 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.37. A method of treating Pneumovirinae virus infection in a human in need thereof claim 22 , the method comprising administering to the human in need thereof a therapeutically effective amount of a compound of claim 22 , or a pharmaceutically acceptable salt thereof.38. The method of claim 37 , wherein the Pneumovirinae virus infection ...

THIENO[3,2-d]PYRIMIDINE, FURO[3,2-d]PYRIMIDINE, AND PYRROLO[3,2-D]PYRIMIDINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds. 2. A compound of wherein X is S claim 1 , or a pharmaceutically acceptable salt thereof.3. A compound of claim 1 , wherein Ris selected from the group of CN claim 1 , OR claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , —CH—O—C-Calkyl claim 1 , —CH—S—C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , azido claim 1 , halogen claim 1 , C-Cchloroalkyl claim 1 , C-Cbromoalkyl claim 1 , and C-Cfluoroalkyl; or a pharmaceutically acceptable salt thereof.4. A compound of claim 1 , wherein Ris selected from the group of H claim 1 , CH claim 1 , F claim 1 , Cl claim 1 , and NH; Ris selected from the group of OH claim 1 , F claim 1 , Cl claim 1 , N claim 1 , NH claim 1 , and CN; and Ris selected from the group of CN claim 1 , N claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , vinyl claim 1 , propenyl claim 1 , ethynyl claim 1 , CHF claim 1 , CHF claim 1 , CHCl claim 1 , CHSMe claim 1 , and CHOMe; or a pharmaceutically acceptable salt thereof.8. A compound of wherein X is S claim 7 , or a pharmaceutically acceptable salt thereof.10. A compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris H.11. A compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris F12. A compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris F.13. A compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris Cl.14. A compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein Ris N.15. A compound of claim 9 , or a ...

PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL AGENTS

The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections. 130-. (canceled) This application is a divisional of U.S. patent application Ser. No. 13/722,962, filed Dec. 20, 2012, which claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61/579,625, filed Dec. 22, 2011, and U.S. Provisional Application No. 61/618,510, filed Mar. 30, 2012. The foregoing applications are incorporated herein by reference in their entireties.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The Pneumovirinae sub-family of viruses is a part of the family Paramyxoviridae and includes human respiratory syncytial virus (HRSV). Almost all children will have had an HRSV infection by their second birthday. HRSV is the major cause of lower respiratory tract infections in infancy and childhood with 0.5% to 2% of those infected requiring hospitalization. The elderly and adults with chronic heart, lung disease or those that are immunosuppressed also have a high risk for developing severe HRSV disease (http://www.cdc.gov/rsv/index.html). No vaccine to prevent HRSV infection is currently available. The monoclonal antibody palivizumab is available for immunoprophylaxis, but its use is restricted to infants at high risk, e.g., premature infants or those with either congenital heart or lung disease, and the cost for general use is often prohibitive. In addition, nucleoside analog ribavirin has been approved as the only antiviral agent to treat HRSV infections but has limited efficacy. Therefore, there is a need for anti-Pneumovirinae therapeutics.Provided herein are methods and compounds for the treatment of infections caused by the Pneumovirinae virus family.Accordingly, ...

Methods for treating arenaviridae and coronaviridae virus infections

Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 2. The method according to claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , butenylene claim 1 , ethylene claim 1 , propylene claim 1 , butylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene or pyrimidinylene.3. The method according to claim 1 , wherein Ais isoquinolinylene claim 1 , phenylene or halophenylene.4. The method according to claim 1 , wherein Xis —O— or —NH—; one of Rand Ris H and the other is methyl; Ris iso-propyl; Ris methyl and Ris H or methyl.5. The method according to claim 1 , wherein Ris H or methyl; Ris H; Ris H claim 1 , —OH claim 1 , methoxy claim 1 , trifluoroethoxy; and Ris H.7. The method according to claim 6 , wherein Ais heteroarylene; Ais (C-C)alkylene claim 6 , (C-C)alkenylene claim 6 , (C-C)alkynylene claim 6 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or (C-C)alkyl; and Ris H claim 6 , —OH or (C-C)alkoxy.9. The method according to claim 6 , wherein Ais arylene; and Ais (C-C)alkylene claim 6 , (C-C)alkenylene claim 6 , (C-C)alkynylene claim 6 , —O—(C-C)alkylene claim 6 , —O—(C-C)alkenylene claim 6 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or (C-C)alkyl; and Ris H claim 6 , —OH claim 6 , C)alkoxy or halo(C-C)alkoxy.11. The method of claim 6 , wherein Ais arylene; and Ais pyrazolylene claim 6 , phenylene or pyrimidinylene.13. The method according to claim 1 , wherein Ais haloarylene; and Ais —O—(C-C)alkylene or —O—(C-C)alkenylene.17. (canceled)18. (canceled)19. (canceled)20. (canceled)21. The method of claim 1 , wherein the viral infection is caused by a Hepatitis C virus.22. The method of claim 1 , wherein the viral infection causes a disease selected from the group consisting of dengue fever claim 1 , yellow fever claim 1 , hepatitis C claim 1 , Japanese encephalitis claim 1 , Kyasanur forest disease claim 1 , Murray valley encephalitis claim 1 , St. Louis encephalitis claim 1 , ...

THIENO[3,2-d]PYRIMIDINE, FURO[3,2-d]PYRIMIDINE, AND PYRROLO[3,2-D]PYRIMIDINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds. 14-. (canceled)6. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris Cl.7. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris NH.8. (canceled)9. The compound of claim 5 , or the pharmaceutical acceptable salt thereof wherein Ris H.10. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris H.11. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris F.12. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris F.13. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris Cl.14. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris N.15. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris selected from the group consisting of CN and N.16. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris selected from the group consisting of methyl claim 5 , ethyl claim 5 , and propyl.17. The compound of claim 5 , or the pharmaceutically acceptable salt thereof claim 5 , wherein Ris selected from the group consisting of CHF claim 5 , CHF claim 5 , and CHCl.23. A method of treating a Pneumoviridae virus infection in a human in need thereof claim 5 , the method comprising administering to the human a therapeutically effective amount of the compound of claim 5 , or the pharmaceutically acceptable salt thereof. ...

COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

COMPOUNDS AND METHODS FOR ANTIVIRAL TREATMENT

Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections. 2. The compound of wherein:{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'a) Yis N, NH or CH, Yis C, Yis N or CR, Yis N or C and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '8′', '4', '5', '2′', '1', '2', '3', '4', '5', '2′, 'b) Yis N, NH or CH, Yis N or C, Yis N or CR, Yis N or C, and Yis N or NR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR; or'}{'sup': 1', '2', '3', '8′', '4', '5', '2′', '2', '1', '2', '3', '4', '5', '2′, 'c) Yis N, NH or CH, Yis N or C, Yis CR, Yis N or C, and Yis N, NR or CR, wherein at least two of Y, Y, Y, Yand Yare independently N, NH or NR;'}the dashed bonds ---- are selected from single bonds and double bonds so as to provide an aromatic ring system;{'sup': 4', '4′', '4', '4′', '4', '4′', 'a, 'sub': n', 'n', 'p, 'A is —(CRR)— wherein any one CRR of said —(CRR)— may be optionally replaced with —O—, —S—, —S(O)—, NH or NR;'}n is 3, 4, 5 or 6;each p is 1 or 2;{'sub': 2', '20', '6', '20', '2', '20', '6', '20, 'sup': '6', 'Ar is a C-Cheterocyclyl group or a C-Caryl group, wherein the C-Cheterocyclyl group or the C-Caryl group is optionally substituted with 1 to 5 R;'}{'sup': 13', '14', '14, 'sub': '2', 'X is —C(R)(R)—, —N(CHR)— or —NH—, or X is absent;'}{'sup': 1', '11', '11', '12', '11', '11', '11', '11', '11', '11', '12', '11', 'a', '11', 'a', '11', '11', '11', '12', '11', '11', '11', '12', '11', '11', '11', '11', '12', '11', '11', '11', '12, 'sub': 3', '2', 'p', 'p', 'p', '2', 'p', 'p', '1', '8', '2', '8', '2', '8', '1', '8', '6', '20', '2', '20', '2', '20', '1', '8', ...

PYRROLO[1,2-f][1,2,4]TRIAZINES USEFUL FOR TREATING RESPIRATORY SYNCITIAL VIRUS INFECTIONS

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. 2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein both Rand Rare H claim 1 , and Ris OH.3. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein both Rand Rare H claim 1 , Ris F.5. A compound according to claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Ris CN claim 4 , methyl claim 4 , ethyl claim 4 , ethenyl claim 4 , ethynyl claim 4 , azido claim 4 , F claim 4 , Cl claim 4 , —CHCl claim 4 , —CHF claim 4 , —CHF claim 4 , or —CF.6. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris F.7. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris OH.8. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris F and Ris CN.9. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris OH and Ris CN.10. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris F claim 5 , and Ris methyl claim 5 , ethyl claim 5 , vinyl claim 5 , or ethynyl.11. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris OH claim 5 , and Ris methyl claim 5 , ethyl claim 5 , vinyl claim 5 , or ethynyl.12. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris F and Ris halomethyl.13. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris OH and Ris halomethyl.14. A ...

METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: 124-. (canceled)27. The pharmaceutical composition of claim 26 , comprising at least one other therapeutic agent.28. The pharmaceutical composition of claim 27 , wherein the at least one other therapeutic agent is selected from the group consisting of parenteral fluids claim 27 , antibiotics claim 27 , antifungals claim 27 , fever and pain medication claim 27 , antiemetics claim 27 , antidiarrheal agents claim 27 , vitamin and mineral supplements claim 27 , anti-inflammatory agents claim 27 , and anti-malarial agents; or mixtures thereof.29. The pharmaceutical composition of claim 27 , wherein the at least one other therapeutic agent is selected from the group consisting of ribavirin claim 27 , palivizumab claim 27 , motavizumab claim 27 , RSV-IGIV claim 27 , MEDI-557 claim 27 , A-60444 claim 27 , MDT-637 claim 27 , BMS-433771 claim 27 , amiodarone claim 27 , dronedarone claim 27 , verapamil claim 27 , Ebola Convalescent Plasma (ECP) claim 27 , TKM-100201 claim 27 , (2S claim 27 ,3S claim 27 ,4R claim 27 ,5R)-2-(4-amino-5H-pyrrolo[3 claim 27 ,2-d]pyrimidin-7-yl)-5-(hydroxymethyl)pyrrolidine-3 claim 27 ,4-diol claim 27 , favipiravir claim 27 , T-705 monophosphate claim 27 , T-705 diphosphate claim 27 , T-705 triphosphate claim 27 , 1-N claim 27 ,7-N-bis[3-(dimethylamino)propyl]-3 claim 27 ,9-dimethylquinolino[8 claim 27 ,7-h]quinolone-1 claim 27 ,7-diamine claim 27 , JK-05 claim 27 , TKM-Ebola claim 27 , ZMapp claim 27 , rNAPc2 claim 27 , VRC-EBOADC076-00-VP claim 27 , OS-2966 claim 27 , MVA-BN filo claim 27 , brincidofovir claim 27 , Vaxart adenovirus vector 5-based ebola vaccine claim 27 , Ad26-ZEBOV claim 27 , FiloVax vaccine claim 27 , GOVX-E301 claim 27 , GOVX-E302 claim 27 , ebola virus entry inhibitors (NPC1 inhibitors) claim 27 , and rVSV-EBOV; or mixtures thereof.31. ...

Pyrrolo[1,2-f][1,2,4]triazines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds.

Methods for the preparation of ribosides

Provided are methods of preparing compounds and pharmaceutical compositions comprising a compound Formula VIII for treating Filoviridae virus infections. In one aspect, the compound of Formula VIII is formed from a reaction mixture comprising the compound of Formula IX, the compound of Formula X, a coupling agent such as magnesium chloride and a non-nucleophilic base such as diisopropylethylamine. The compound of Formula IX can be formed from a compound of Formula V and a cyanating agent. The compound of Formula V can be synthesized from a reaction mixture comprising a deprotonating agent such as phenylmagnesium chloride; a silylating agent such as chlorotrimethylsilane; a coupling agent such as isopropylmagnesium chloride, an additive such as LaCl3-2LiCl, LaCl3, CeCl3, NdCl3, or YCl3; a compound of Formula VI; and 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine. The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-D]pyrimidines useful for treating respiratory syncitial virus infections

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds.

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.4. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sub': 3', '6', '3', '6', '1', '4', '1', '3, '{circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons, wherein said C-Ccarcbocyclene is optionally substituted with C-Calkyl or C-Chaloalkyl.'}5. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein the C-Ccarcbocyclene is optionally substituted with methyl claim 1 , ethyl or trifluoromethyl.6. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is cyclopropylene.7. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein {circle around (T)} is C-Cbridged bicyclic carbocyclylene or C-Cfused bicyclic carbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons.8. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically ...

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 2. The compound of claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , butenylene claim 1 , ethylene claim 1 , propylene claim 1 , butylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene or pyrimidinylene.3. The compound of claim 1 , wherein Ais isoquinolinylene claim 1 , phenylene or halophenylene.4. The compound of claim 1 , wherein Xis —O— or —NH—; one of Rand Ris H and the other is methyl; Ris iso-propyl; Ris methyl and Ris H or methyl.5. The compound of claim 1 , wherein Ris H or methyl; Ris H; Ris H claim 1 , —OH claim 1 , methoxy claim 1 , or trifluoroethoxy; and Ris H.7. The compound of claim 1 , wherein Ais heteroarylene; Ais (C-C)alkylene claim 1 , (C-C)alkenylene claim 1 , or (C-C)alkynylene claim 1 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or (C-C)alkyl; and Ris H claim 1 , —OH or (C-C)alkoxy.9. The compound of claim 1 , wherein Ais arylene; and Ais (C-C)alkylene claim 1 , (C-C)alkenylene claim 1 , (C-C)alkynylene claim 1 , —O—(C-C)alkylene claim 1 , or —O—(C-C)alkenylene claim 1 , wherein Ais optionally substituted with one or more (C-C)alkyl; Ris H or (C-C)alkyl; and Ris H claim 1 , —OH claim 1 , (C-C)alkoxy or halo(C-C)alkoxy.11. The compound of claim 1 , wherein Ais arylene; and Ais pyrazolylene claim 1 , phenylene or pyrimidinylene.13. The compound of claim 1 , wherein Ais haloarylene; and Ais —O—(C-C)alkylene or —O—(C-C)alkenylene.17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , isotope claim 1 , stereoisomer claim 1 , mixture of stereoisomers claim 1 , tautomer claim 1 , ester or prodrug thereof and a pharmaceutically acceptable excipient.18. The pharmaceutical composition of claim 17 , further comprising at least one additional therapeutic agent selected from the group consisting of interferons claim 17 , ribavirin claim 17 , HCV ...

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 2. The compound of claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , butenylene claim 1 , ethylene claim 1 , propylene claim 1 , butylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene or pyrimidinylene.3. The compound of claim 1 , wherein Ais —CH(R)-quinolinylene claim 1 , —CH(R)-isoquinolinylene claim 1 , —CH(R)-naphthyridinylene claim 1 , —CH(R)-cinnolinylene claim 1 , —CH(R)-quinoxalinylene claim 1 , —CH(R)-phenylene or —CH(R)-halophenylene.4. The compound of claim 1 , wherein Ris methyl.5. The compound of claim 1 , wherein Xis —O— claim 1 , —NH— or —N(CH)—; Rand R claim 1 , when taken together with the carbon to which they are both attached claim 1 , form —C(═O)—; and Ris H.6. The compound of claim 1 , wherein Xis —O— claim 1 , —NH— or —N(CH)—; Rand R claim 1 , when taken together with the carbon to which they are both attached claim 1 , form —C(═O)—; Ris H; one of Rand Ris H and the other is methyl; and one of Rand Ris H and the other is isopropyl.7. The compound of claim 1 , wherein Xis —O— claim 1 , —NH— or —N(CH)—; Rand R claim 1 , when taken together with the carbon to which they are both attached claim 1 , form —C(═O)—; Ris H; one of Rand Ris H and the other is methyl; one of Rand Ris H and the other is isopropyl; Ais —CH(R)-heteroarylene; and Ris methyl.8. The compound of claim 1 , wherein one of Rand Ris H; and the other H claim 1 , hydroxyl claim 1 , —CHCHCR(═N(C-C)alkoxy) claim 1 , (C-C)alkyl or (C-C)alkoxy claim 1 , wherein Ror Ris optionally substituted with one or more substituents selected from the group consisting of halo claim 1 , hydroxyl claim 1 , (C-C)alkoxy claim 1 , halo(C-C)alkoxy claim 1 , heterocycloalkyl claim 1 , (C-C)alkanoyl and di(C-C)alkylamino.28. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , isotope claim 1 , stereoisomer claim 1 , mixture of ...

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

INHIBITORS OF HEPATITIS C VIRUS

Compounds of Formula I are disclosed, As well as pharmaceutically acceptable salts thereof. Methods of using said compounds and pharmaceutical compositions containing said compounds are also disclosed. 2. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is C-Calkyl.3. The compound of claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein J is methyl or ethyl.4. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein said C-Ccarcbocyclene is optionally substituted with C-Calkyl or C-Chaloalkyl.5. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein is C-Ccarbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons claim 1 , wherein the C-Ccarcbocyclene is optionally substituted with methyl claim 1 , ethyl or trifluoromethyl.6. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein is cyclopropylene.7. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of stereoisomers claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein is C-Cbridged bicyclic carbocyclylene or C-Cfused bicyclic carbocyclylene that is attached to L and to the remainder of the compound of Formula IV through two adjacent carbons.8. The compound of any one of to claim 1 , or a stereoisomer claim 1 , or a mixture of ...

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

2'-CHLORO AMINOPYRIMIDINONE AND PYRIMIDINE DIONE NUCLEOSIDES

Provided herein are formulations, methods and substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds. 221-. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/040,349, filed on Aug. 21, 2014, which is hereby incorporated by reference in its entirety.Provided herein are substituted 2′-chloro aminopyrimidinone and pyrimidine dione compounds, methods and pharmaceutical formulations for treating Pneumovirinae virus infections, particularly including respiratory syncytial virus infections, and methods and intermediates useful for preparing the compounds.Pneumovirinae viruses are negative-sense, single-stranded, RNA viruses that are responsible for many prevalent human and animal diseases. The Pneumovirinae sub-family of viruses is a part of the family Paramyxoviridae and includes human respiratory syncytial virus (HRSV). Almost all children will have had an HRSV infection by their second birthday. HRSV is the major cause of lower respiratory tract infections in infancy and childhood with 0.5% to 2% of those infected requiring hospitalization. The elderly and adults with chronic heart, lung disease or those that are immunosuppressed also have a high risk for developing severe HRSV disease (http://www.cdc.gov/rsv/index.html). No vaccine to prevent HRSV infection is currently available. The monoclonal antibody palivizumab is available for immunoprophylaxis, but its use is restricted to infants at high risk, e.g., premature infants or those with either congenital heart or lung disease, and the cost for general use is often prohibitive. In addition, nucleoside analog ribavirin has been approved as the only antiviral agent to treat HRSV infections but has limited efficacy. Therefore, there is a ...

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 2. The method of claim 1 , wherein A is methylene.3. The method of claim 1 , wherein Ais ethenylene claim 1 , propenylene claim 1 , ethylene claim 1 , propylene claim 1 , oxypropylene claim 1 , oxypropenylene claim 1 , pyrazolylene claim 1 , phenylene or pyrimidinylene.5. The method of claim 1 , wherein Ais —CH(R)-arylene or —CH(R)-heteroarylene.6. The method of claim 1 , wherein Ais —CH(R)-quinolinylene claim 1 , —CH(R)-isoquinolinylene claim 1 , —CH(R)-naphthyridinylene claim 1 , —CH(R)-cinnolinylene claim 1 , —CH(R)-quinoxalinylene claim 1 , —CH(R)-phenylene or —CH(R)-halophenylene.8. The method of claim 1 , wherein Xis —O— or —NH—.9. The method of claim 1 , wherein Rand R claim 1 , when taken together with the carbon to which they are both attached claim 1 , form —C(═O)—.10. The method of claim 1 , wherein Ris H.11. The method of claim 1 , wherein Ris H and Ris H or (C-C)alkyl claim 1 , or Rand Rtogether form a spirocycle having Formula (a).13. The method of claim 1 , wherein Ris H; Ris H; Ris H claim 1 , (C-C)alkyl claim 1 , hydroxy(C-C)alkyl claim 1 , (C-C)alkenyl claim 1 , (C-C)alkynyl claim 1 , azido(C-C)alkyl claim 1 , aryl claim 1 , cycloalkyl claim 1 , aryl(C-C)alkyl claim 1 , cycloalkyl(C-C)alkyl claim 1 , heterocycloalkyl(C-C)alkyl or arylheterocycloalkyl(C-C)alkyl; Ris H; and Ris H claim 1 , (C-C)alkyl or hydroxy(C-C)alkyl.14. The method of claim 1 , wherein Xis —O— or —NH—; Rand R claim 1 , when taken together with the carbon to which they are both attached claim 1 , form —C(═O)—; Ris H; Ris H; Ris methyl; Ris H and Ris iso-propyl claim 1 , propenyl or propynyl; and Ris methyl.20. The method of claim 19 , wherein Ais —CH(R)-arylene or —CH(R)-heteroarylene; Ris H; and Ais —CH—.21. The method of claim 19 , wherein Ais —CH(R)-arylene or —CH(R)-heteroarylene; Ris H; and Ais —O—.24. The method of claim 23 , wherein Ais —CH(R)-arylene or —CH(R)-heteroarylene; Ris H; and Ais —O—25. The method of claim 23 , wherein Ais —CH ...

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Provided are compounds of Formula I: 130-. (canceled)32. The method of claim 31 , wherein the viral infection is caused by a Hepatitis B virus or a Hepatitis C virus.33. The method of claim 31 , wherein the viral infection causes a disease selected from the group consisting of dengue fever claim 31 , yellow fever claim 31 , hepatitis C claim 31 , Japanese encephalitis claim 31 , Kyasanur forest disease claim 31 , Murray valley encephalitis claim 31 , St. Louis encephalitis claim 31 , tick-borne encephalitis or West Nile encephalitis.35. The method of claim 34 , wherein the viral infection is caused by a SARS coronarirus.36. The method of claim 31 , wherein the viral infection causes a disease selected from the group consisting of severe acute respiratory syndrome (SARS) claim 31 , cancer claim 31 , inflammation claim 31 , obesity claim 31 , acquired immune deficiency syndrome (AIDS) claim 31 , or cirrhosis. This application claims the benefit under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61/657,562, filed on Jun. 8, 2012, the entirety of which is incorporated herein by reference.The present application provides novel compounds inhibiting viruses, compositions containing such compounds, and therapeutic methods comprising the administration of such compounds.RNA viruses comprising the Flaviviridae family include at least three distinguishable genera including pestiviruses, flaviviruses, and hepaciviruses (Calisher, et al., J. Gen. Virol., 1993, 70, 37-43). While pestiviruses cause many economically important animal diseases such as bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV, hog cholera) and border disease of sheep (BDV), their importance in human disease is less well characterized (Moennig, V., et al., Adv. Vir. Res. 1992, 48, 53-98). Flaviviruses are responsible for important human diseases such as dengue fever and yellow fever while hepaciviruses cause hepatitis C virus infections in humans. Other important viral ...

ANTIVIRAL COMPOUNDS

The present disclosure provides compounds for treating a variety of diseases, such as respiratory syncytial virus (RSV), HRV, hMPV, ebola, Zika, West Nile, Dengue, and HCV. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '2', '1A', '1A', '1', '2, 'Rand Rare each independently H or —C(O)R, wherein Ris methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or t-butyl, wherein at least one of Rand Ris H;'}{'sup': 1', '2, 'sub': '2', 'or Rand Rare combined to form —C(O)—, —C(Me)- or —CH(OEt)-.'}3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '2', '1A', '1A', '1', '2, 'Rand Rare each independently H or —C(O)R, wherein Ris ethyl, iso-propyl or t-butyl, wherein at least one of Rand Ris H;'}{'sup': 1', '2, 'sub': '2', 'or Rand Rare combined to form —C(O)—, —C(Me)- or —CH(OEt)-.'}4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '3', 'sub': '2', 'Ris NH.'}5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '4A', 'Ris O.'}6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '2', '1A', '1A', '1', '2, 'Rand Rare each independently H or —C(O)R, wherein Ris ethyl, iso-propyl or t-butyl, wherein at least one of Rand Ris H;'}{'sup': 1', '2, 'sub': '2', 'or Rand Rare combined to form —C(O)—, —C(Me)- or —CH(OEt)-;'}{'sup': '3', 'sub': '2', 'Ris NH; and'}{'sup': '4A', 'Ris O.'}19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 4G', '4G1', '4G1, 'sub': 2', '2', '2', '3', '3', '2', '2, 'Ris methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentane, neopentane, n-hexane, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethyl-butyl, heptane, octane, nonane, decane, undecane, dodecane, pentadecane, hexadecane, or octadecane, each optionally substituted ...

Compounds and methods for antiviral treatment

Inhibitors of hepatitis C virus

Pyrazolo[1,5-A]pyrimidines as antiviral agents

The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections.

Methods for treating zika virus infections

Provided are methods for treating Zika virus infections by administering a compound of Formula I, Formula II, Formula III, or Formula IV, or combinations thereof.

Synthesis of a macrocyclic HCV NS3 inhibiting tripeptide

The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.

MACROCYCLIC INHIBITORS OF FLAVIVIRIDAE VIRUSES

Se proporcionan compuestos de la Fórmula I y sales farmacéuticamente aceptables y ésteres del mismo. Los compuestos, composiciones, y métodos que se proporcionan son útiles en el tratamiento de las infecciones virales, de forma particular para las infecciones de hepatitis C.

Methods for the preparation of ribosides

Provided are methods of preparing compounds and pharmaceutical compositions for treating Filoviridae virus infections the compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

2'-chloro aminopyrimidinone and pyrimidine dione nucleosides

Provided herein are formulations, methods and substituted 2'-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating

Methods for treating filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Pyrazolo[1,5-a]pyrimidines as antiviral agents

Methods for treating arenaviridae virus infections

Pyrrolo [1,2,f] [1,2,4] triazines useful for treating respiratory syncitial virus infections

C:\Interwo n\NRPortbl\DCC\RBR959687 _.docx-8/06/2019 ABSTRACT OF THE DISCLOSURE Provided herein are formulations, methods and substituted tetrahydrofuranyl pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (1) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and 5 intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. R 2 NH 2 N N RO5 -0 N R R / R3 R 6

Synthesis of a macrocyclic hcv ns3 inhibiting tripeptide

The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds and processes for the preparation of the compounds that are synthetic intermediates to the compound of formula I.

Pyrazolo [1, 5 -a] pyrimidines as antiviral agents

The invention provides compounds of Formula I or Formula II: (I), (II) or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

Pyrrolo [1,2,f] [1,2,4] triazines useful for treating respiratory syncitial virus infections

C:\Interwo n\NRPortbl\DCC\RBR959687 _.docx-8/06/2019 Provided herein are formulations, methods and substituted tetrahydrofuranyl pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds of Formula (1) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and 5 intermediates for synthesis of tetrahydrofuranyl-pyrrolo[1,2-f][1,2,4]triazine-4-amine compounds. RO5 -0 N

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Compounds and methods for antiviral treatment

METHODS TO TREAT INFECTIONS BY VIRUS FILOVIRIDAE

Se proporcionan compuestos, métodos, y composiciones farmacéuticas para tratar infecciones por el virus Filoviridae administrando ribósidos, fosfatos de ribósido, y profármacos del mismo, de Fórmula IV: Fórmula IV. Los compuestos, composiciones, y métodos provistos son particularmente útiles para el tratamiento de infecciones por el virus de Marburg, virus de Ebola y virus Cueva.

Methods for treating filoviridae virus infections

The invention relates generally to uses and compounds for treating Filoviridae virus infections such as Marburg virus, Ebola virus and Cueva virus infections. Provided are ribosides, riboside phosphates and prodrugs thereof of Formula IV:

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula (I) and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Pyrazolo [1,5-a] pyrimidines as antiviral agents

The invention provides compounds of Formula I or Formula II: (I), (II) or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.

2'-chloro aminopyrimidinone and pyrimidine dione nucleosides

Provided herein are formulations, methods and substituted 2'-chloro aminopyrimidinone and pyrimidine dione compounds of Formula (I) for treating

Macrocyclic inhibitors of flaviviridae viruses

Provided are compounds of Formula I: and pharmaceutically acceptable salts and esters thereof. The compounds, compositions, and methods provided are useful for the treatment of virus infections, particularly hepatitis C infections.

Inhibitors of hepatitis c virus

use of an antiviral compound or salt thereof for the treatment of a coronaviridae infection

são fornecidos métodos para o tratamento de infecções pelos vírus arenaviridae e coronaviridae administrado nucleosídeos e pró-fármacos dos mesmos, de fórmula i: , em que a posição 1' do açúcar de nucleosídeo é substituído. os compostos, composições e métodos fornecidos são particularmente úteis para o tratamento de infecções pelo vírus lassa e vírus junin. methods are provided for the treatment of infections by the arenaviridae and coronaviridae viruses administered nucleosides and prodrugs thereof, of formula i:, in which the 1 'position of the nucleoside sugar is substituted. the compounds, compositions and methods provided are particularly useful for the treatment of infections by the lassa virus and the junin virus.

Methods for the preparation of ribosides

Provided are methods of preparing compounds and pharmaceutical compositions for treating

Macrocyclic inhibitors of flaviviridae viruses.

Se proporcionan compuestos de la Fórmula I: (ver Fórmula) y sales y ésteres farmacéuticamente aceptables de los mismos. Los compuestos, composiciones, y métodos proporcionados son útiles para el tratamiento de infecciones por virus, particularmente infecciones por hepatitis C.