NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula (I).

ANTIVIRAL COMPOUNDS

The present invention is related to compounds of formula (I): E1a-V1a -C(=O)-P1a -W1a -P1b -C(=O)-V1b -E1b (I) wherein W1a is (see above formula ) and E1a, V1a, P1a, P1b, V1b and E1b are as described herein, compositions containing such compounds, anti-viral uses of such compounds, as well as to processes and intermediates useful for preparing such compounds.

COMBINATION FORMULATION OF TWO ANTIVIRAL COMPOUNDS

Disclosed are pharmaceutical compositions having an effective amount of substantially amorphous ledipasvir and an effective amount of substantially crystalline sofosbuvir.

Process for the preparation of a fluorolacton derivative

The acylated fluor lactones of formula V, particularly the benzoyl derivative with R1=benzyl are important precursors for the synthesis of prodrug compounds which have the potential to be potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.

PREPARATION OF 2'≡FLUORO-2'-ALKYL-SUBSTITUTED OR OTHER OPTIONALLY SUBSTITUTED RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

... ²The present invention provides (i) processes for preparing a ²2'-deoxy-2'-fluoro-2'-methyl-D-ribonolactone derivatives, (ii) conversion of ²intermediate lactones to ²nucleosides with potent anti-HCV activity, and their analogues, and (iii) ²methods to ²prepare the anti-HCV nucleosides containing the ²2'-deoxy-2'-fluoro-2'-C-methyl-.beta.-D-ribofuranosyl ²nucleosides from a preformed, preferably naturally-occurring, ²nucleoside.²(see formula 49B)² ...

CONDENSED IMIDAZOLYLIMIDAZOLES AS ANTIVIRAL COMPOUNDS

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Nucleosidphosphoramidat-Propharmaka

Verbindung gemäß der folgenden Formel:wobei (a) R1 Wasserstoff, Methyl, Ethyl, n-Propyl, i-Propyl oder ein substituiertes oder unsubstituiertes Phenyl ist, wobei der Substituent des substituierten Phenyls mindestens einer von einem CH3, OCH3, F, Cl, Br, I, Nitro, Cyano und einem CH3-qXq ist, wobei X F, Cl, Br oder I ist und q 1–3 ist; (b) R2 Wasserstoff oder CH3 ist; (c) R3a H und R3b H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-Imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, oder Niedercycloalkyl ist; oder R3a CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-Indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-Imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH oder Niedercycloalkyl ist und R3b H ist; (d) R4 Wasserstoff, CH3, Et, iPr, nPr, nBu, 2-Butyl, tBu, Benzyl, Cyclopropyl, Cyclobutyl ...

ANTIVIRAL COMPOUNDS

The disclosure is related to anti-viral compounds of formula (I), compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

N-[(2'R)-2'-DEOXY-2'-FLUORO-2'-METHYL-P-PHENYL-5'-URIDYLYL]-L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION

Disclosed herein are processes for preparing a compound represented by formula 4 and which comprises: a) reacting an isopropyl-alanate, A, a di-X'-phenylphosphate, B, 2'-deoxy-2'-fluoro-2'-C-methyluridine, 3, and a base to obtain a first mixture comprising 4, or the phosphorous-based diastereomer thereof, b) reacting the first mixture with a protecting compound to obtain a second mixture comprising 4, or the phosphorous-based diastereomer thereof, and a protected side product, wherein the protecting compound is t-butyl-dimethyl-silyl-chloride; and c) subjecting the second mixture to crystallization, chromatography, or extraction in order to obtain 4, or the phosphorous-based diastereomer thereof.

ANTIVIRAL COMPOUNDS

The invention relates to anti-viral compounds, compositions containing such compounds, and therapeutic uses of such compounds, as well as to processes and intermediates useful for preparing such compounds. Representative compounds include compounds of formula I: (see formula I)

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

2',4'-SUBSTITUTED NUCLEOSIDES AS ANTIVIRAL AGENTS

Embodiments of the invention are to compounds of formulae (A), (A), methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention aur 2',4'-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

PREPARATION OF ALKYL-SUBSTITUTED 2-DEOXY-2-FLUORO-D-RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

The present invention provides (i) a process for preparing a 2-deoxy-2-fluro-2-methyl-D-ribonolactone derivative of the formula defined below, (ii) conversion of the lactone to nucleosides with potent anti-HCV activity, and their analogues, and (iii) a method to prepare the anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-.beta.-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside. (see above formula) ...

Nucleoside cyclicphosphates

Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure:

COMPOSITIONS AND METHODS FOR TREATING HEPATITIS C VIRUS

Disclosed herein are a composition and unit dosage form for the treatment of hepatitis C virus (HCV) infection comprising GS-7977 and at least one pharmaceutically acceptable excipient, as well as methods for making said composition and unit dosage form. Also disclosed herein is a method of treating a subject, preferably a human, infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period.

NUCLEOSIDE PHOSPHORAMIDATES

It is provided a compound represented by formula I, or a stereoisomer, salt, or pharmaceutically acceptable salt thereof: (See Above Formula) wherein Z is (See Above Formula) R1 is hydrogen or phenyl; R2 is hydrogen; R3a is hydrogen; R3b is CH3; R4 is hydrogen or cyclopentyl; R5 is hydrogen; R6 is CH3; X is F; R8 is OCH3, -N(-CH2CH2CH2-), -OBn, or OH; and R9 is NH2 for the treatment against Hepatitis C virus.

MODIFIED 4'-NUCLEOSIDES AS ANTIVIRAL AGENTS

Compounds, methods and compositions for treating a host infected with human immunodeficiency virus and hepatitis B virus comprising administering an effective amount of a described 4'-C-substituted /3-D- and /3-L-nucleoside or a pharmaceutically acceptable salt or prodrug thereof, are provided.

MODIFIED 4'-NUCLEOSIDES AS ANTIVIRAL AGENTS

Antiviral compounds

Processes for preparing antiviral compounds

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

NUCLEOSIDE PHOSPHORAMIDATES

Nucleoside phosphoramidates

STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS CONTAINING ACTIVES

Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same. A process for preparing a composition comprising an enantiomerically- or a diastereomerically-enriched phosphorus-containing active, salt, or pharmaceutically acceptable salt thereof, of formula I is disclosed: 1 which comprises a) reacting a protected or unprotected Active with a base to form a salt of said active and then reacting said salt with an enantiomerically- or a diastereomerically enriched compound of formula II wherein Group is as defined herein, W is an aryl or -CCH2)nSC(O)C(CH3)m(CH2OH)3-m, where n is 2 or 3 and m is 0, 1, 2, or 3, and LG is a leaving group; b) optionally deprotecting the compound obtained in step a) and c) optionally subjecting the compound obtained in step a) or the compound obtained in step b) to chromatography, ...

SYNTHESIS OF HEPATITIS C ANTIVIRAL FLUORENYL-BENZIMIDAZOLE DERIVATIVES COMPOUNDS

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

SOLID FORMS OF AN ANTIVIRAL COMPOUND

Crystalline solid forms of methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2- [(methoxycarbonyl)amino] -2-phenylacetyl} -4-(methoxymethyl)pyrrolidin-2-yl] - 1 H-imidazol-5 - yl} -1, 11 -dihydroisochromeno[4',3':6,7]naphtho[ 1,2-d]imidazol-2-yl)-5-methylpyrrolidin- 1 -yl]-3- methyl-l-oxobutan-2-yl} carbamate (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using these crystalline forms.

COMBINATION FORMULATION OF TWO ANTIVIRAL COMPOUNDS

Disclosed are pharmaceutical compositions comprising Compound I, having the formula (I): and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.

MODIFIED FLUORINATED NUCLEOSIDE ANALOGUES

The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof. 1129-. (canceled) This application claims the benefit, pursuant to 35 U.S.C. §119(e), of provisional U.S. Patent Application Ser. No. 60/474,368, filed May 30, 2003, the disclosure of which is hereby incorporated herein in its entirety by reference.The present invention includes (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides having the natural β-configuration and methods for the treatment of Flaviviridae infections, especially hepatitis C virus (HCV).Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population. There are an estimated 4.5 million infected people in the United States alone, according to the U.S. Center for Disease Control. According to the World Health Organization, there are more than 200 million infected individuals worldwide, with at least 3 to 4 million people being infected each year. Once infected, about 20% of people clear the virus, but the rest can harbor HCV the rest of their lives. Ten to twenty percent of chronically infected individuals eventually develop liver-destroying cirrhosis or cancer. The viral disease is transmitted parenterally by contaminated blood and blood products, contaminated needles, or sexually and vertically from infected mothers or carrier mothers to their offspring. Current treatments for HCV infection, which are restricted to immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin, are of limited clinical benefit as resistance develops ...

PROCESSES FOR PREPARING ANTIVIRAL COMPOUNDS

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

NUCLEOSIDE CYCLICPHOSPHATES

Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure: Formula (I) ...

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphoramidates and their use as an agents for treating viral diseases. More particularly, it is disclosed the phosphorus-based diastereomers (see formula I) or crystalline (S)-isopropyl 2-(((S)-(perfluorophenoxy)(phenoxy)phosphoryl)amino)propanoate represented by the formula (see formula II) These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

N- [(2'R) -2'-DEOXY-2'-FLUORO-2' -METHYL-P-PHENYL-5' -URIDYLYL] -L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION

Disclosed herein are processes for preparing a compound represented by formula 4 and which comprises: a) reacting an isopropyl-alanate, A, a di-X'-phenylphosphate, B, 2'-deoxy-2'-fluoro-2'-C-methyluridine, 3, and a base to obtain a first mixture comprising 4, or the phosphorous-based diastereomer thereof; b) reacting the first mixture with a protecting compound to obtain a second mixture comprising 4, or the phosphorous-based diastereomer thereof, and a protected side product, wherein the protecting compound is t-butyl-dimethyl-silyl-chloride; and c) subjecting the second mixture to crystallization, chromatography, or extraction in order to obtain 4, or the phosphorous-based diastereomer thereof.

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphorainidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

TREATMENT OF EBV AND KHSV INFECTION AND ASSOCIATED ABNORMAL CELLULAR PROLIFERATION

A method and composition for the treatment, prevention and/or prophylaxis of a host, and in particular, a human, infected with Epstein-Barr virus (EBV), is provided that includes administering an effective amount of a 5-substituted uracil nucleoside or its pharmaceutically acceptable salt or prodrug, optionally in a pharmaceutically acceptable diluent or excipient.

N- [(2'R) -2'-DEOXY-2'-FLUORO-2' -METHYL-P-PHENYL-5' -URIDYLYL] -L-ALANINE 1-METHYLETHYL ESTER AND PROCESS FOR ITS PRODUCTION

Provided herein is a process for preparing the compound of formula Sp-4: (see formula Sp-4) ...

Nucleoside phosphoramidates

PROCESS FOR THE PREPARATION OF 2-DEOXY-2-FLUORO-2-METHYL-D-RIBOFURANOSYL NUCLEOSIDE COMPOUNDS

LEDIPASVIR D-TARTRATE

2',4'-SUBSTITUTED NUCLEOSIDES AS ANTIVIRAL AGENTS

Antiviral compounds

COMPOSED ANTIVIRALS

Solid forms of an antiviral compound

Crystalline solid forms of methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)pyrrolidin-2-yl]-1H-imidazol-5-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using these crystalline forms.

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Synthesis of 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 that are synthetic intermediates to compounds of formula I.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions comprising Compound I, having the formula: and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.

Synthesis of purine nucleosides

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

2′,4′-substituted nucleosides as antiviral agents

Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2′,4′-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

PROCESS FOR THE PRODUCTION OF SOFOSBUVIR

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Nucleoside phosphoramidates

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Antiviral compounds

2,4-substituted nucleosides as antiviral agents

Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2,4-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Zusammensetzungen zur Behandlung von HCV

Zusammensetzung für die Verwendung zur Behandlung einer Genotyp 1 HCV Infektion, umfassend: eine Verbindung 10oder ein pharmazeutisch verträgliches Salz davon und eine Verbindung 6oder ein pharmazeutisch verträgliches Salz davon, wobei die Behandlung weder die Verabreichung von Interferon noch von Ribavirin einschließt, wobei die Behandlung von 28 Tagen bis etwa 24 Wochen, vorzugsweise von etwa 12 bis etwa 24 Wochen dauern kann.

Zusammensetzungen zur Behandlung von HCV

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

2'-SPIRO-NUCLEOSIDES FOR USE IN THE THERAPY OF HEPATITIS C

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. 181.-. (canceled)83. The process of claim 82 , wherein Z is hydrogen.84. The process of claim 82 , wherein the leaving group is an aryloxide substituted with at least one electron withdrawing group.85. The process of claim 82 , wherein the leaving group is p-nitrophenoxide claim 82 , 2 claim 82 ,4-dinitrophenoxide claim 82 , or pentafluorophenoxide.86. The process of claim 82 , wherein no chromatography is performed.88. The process of claim 87 , wherein Z is hydrogen.89. The process of claim 87 , wherein the leaving group is an aryloxide substituted with at least one electron withdrawing group.90. The process of claim 87 , wherein the leaving group is p-nitrophenoxide claim 87 , 2 claim 87 ,4-dinitrophenoxide claim 87 , or pentafluorophenoxide.91. The process of claim 87 , wherein no chromatography is performed. The right of priority is claimed to U.S. Provisional Patent Application Nos. 61/179,923, filed May 20, 2009, and 61/319,513, filed Mar. 31, 2010, the subject matter of which is incorporated by reference in its entirety.Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population. There are an estimated 4.5 million infected people in the United States alone, ...

NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

AND PROCEDURE FOR the PREPARATION Of the FOREIGN 1-METILETILICO OF n-N- [(2 ' R) - 2 ' - deossi-2'-DEOSSI-2'- fluorine-2' metil-p-fenil-5'-METIL-P-FENIL-5'- URIDILlL] - L-ALANINA

Preparation of alkyl-substituted 2-deoxy-2-fluoro-D-ribofuranosyl pyrimidines and purines and their derivatives

The present invention provides (i) a process for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivative, (ii) conversion of the lactone to nucleosides with potent anti-HCV activity, and their analogues, and (iii) a method to prepare the anti-HCV nucleosides containing the 2-deoxy-2-fluoro-2-C-methyl-beta-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions having an effective amount of substantially amorphous ledipasvir and an effective amount of substantially crystalline sofosbuvir.

Zusammensetzungen zur Behandlung von HCV

Zusammensetzung für die Verwendung zur Behandlung einer Genotyp 1 HCV Infektion, umfassend eine Verbindung 6und ferner umfassend eine zweite Verbindung ausgewählt aus der Gruppe bestehend aus Verbindung 1, Verbindung 4, Verbindung 5 und Verbindung 7,wobei die Behandlung weder die Verabreichung von Interferon noch von Ribavirin einschließt, und wobei die Behandlung von 28 Tagen bis etwa 24 Wochen, vorzugsweise von etwa 12 bis etwa 24 Wochen dauern kann.

2',4'-SUBSTITUTED NUCLEOSIDES AS ANTIVIRAL AGENTS

CRYSTALLINE (S)-ISOPROPYL 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1-(2H)-YL)-4-FLUORO-3-HYDROXY-4-METHYLTETRAHYDROFURAN-2-YL)METHOXY)(PHENOXY)PHOSPHORYL)AMINO)PROPANOATE

COMPOSED ANTIVIRALS

MODIFIED FLUORINATED NUCLEOSIDE ANALOGUES

PROCESS FOR THE PREPARATION OF A FLUOROLACTON DERIVATIVE

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Preparation of 2′-fluoro-2′-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives

The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-ß-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

Methods for treating HCV

This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

Processes for preparing antiviral compounds

COMPOSITIONS AND METHODS FOR TREATING HEPATITIS C VIRUS

Disclosed herein are a composition and unit dosage form for the treatment of hepatitis C virus (HCV) infection comprising GS-7977 and at least one pharmaceutically acceptable excipient, as well as methods for making said composition and unit dosage form. Also disclosed herein is a method of treating a subject, preferably a human, infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period. 1. A pharmaceutical composition comprising:a) about 25% to about 35% w/w of GS-7977; andb) at least one pharmaceutically acceptable excipient.2. The composition according to claim 1 , wherein the composition comprises about 30% to about 35% w/w of GS-7977.3. The composition according to claim 1 , wherein the composition comprises about 30% w/w of GS-7977.4. The composition according to claim 1 , wherein the composition comprises about 33% w/w of GS-7977.5. The composition according to claim 1 , wherein the composition comprises crystalline GS-7977.6. The composition according to claim 5 , wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:(1) 5.2, 7.5, 9.6, 16.7, 18.3, and 22.2;(2) 5.0, 7.3, 9.4, and 18.1;(3) 4.9, 6.9, 9.8, 19.8, 20.6, 24.7, and 26.1;(4) 6.9, 9.8, 19.7, 20.6, and 24.6;(5) 5.0, 6.8, 19.9, 20.6, 20.9, and 24.9;(6) 5.2, 6.6, 7.1, 15.7, 19.1, and 25.0; or(7) 6.1, 8.2, 10.4, 12.7, 17.2, 17.7, 18.0, 18.8, 19.4, 19.8, 20.1, 20.8, 21.8, and 23.3.7. The composition according to claim 6 , wherein the crystalline GS-7977 has XRPD 2θ-reflections (°) at about:(1) 5.0, 7.3, 9.4, and 18.1; or(2) 6.1, 8.2, 10.4, ...

ANTIVIRAL COMPOUNDS

ANTIVIRAL COMPOUNDS

CRYSTALLINE (S)-ISOPROPYL 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1-(2H)-YL)-4-FLUORO-3-HYDROXY-4-METHYLTETRAHYDROFURAN-2-YL)METHOXY)(PHENOXY)PHOSPHORYL)AMINO)PROPANOATE

Processes for preparing antiviral compounds

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

Nucleoside phosphoramidates

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

SYNTHESIS OF PURINE NUCLEOSIDES

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodmgs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof(No suitable figure) ...

Combination formulation of two antiviral compounds

Methods for treating HCV

This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

Process for the preparation of a fluorolacton derivative

The acylated fluorolactones of formula V, particularly the benzoyl derivative with R1=benzyl are important precursors for the synthesis of prodrug compounds which have the potential to be potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.

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.

Purine nucleoside phosphoramidate

Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

CRYSTALLINE FORMS OF A MACROCYCLIC HCV NS3 INHIBITING TRIPEPTIDE

PREPARATION OF 2'FLUORO-2'-ALKYL-SUBSTITUTED OR OTHER OPTIONALLY SUBSTITUTED RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

ANTIVIRAL COMPOUNDS

Preparation of nucleosides ribofuranosyl pyrimidines

The present process provides an improved method for the preparation of 4-amino-1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydrofuran-2-yl)-1H-pyrimidin-2-one of the formula (IV) which is a potent inhibitor of Hepatitis C Virus (HCV) NS5B polymerase.

PREPARATION OF NUCLEOSIDES RIBOFURANOSYL PYRIMIDINES

COMBINATION FORMULATION OF TWO ANTIVIRAL COMPOUNDS

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

NUCLEOSIDE CYCLICPHOSPHATES

Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure: 3. A composition for the treatment and/or prophylaxis of any of the viral agents disclosed herein said composition comprising a pharmaceutically acceptable medium selected from among an excipient claim 1 , carrier claim 1 , diluent claim 1 , and equivalent medium and the compound of .4. A composition for the treatment and/or prophylaxis of any of the viral agents disclosed herein said composition comprising a pharmaceutically acceptable medium selected from among an excipient claim 2 , carrier claim 2 , diluent claim 2 , and equivalent medium and the compound of .5. A use of the compound of in the manufacture of a medicament for the treatment of any condition the result of an infection by hepatitis C virus claim 1 , West Nile virus claim 1 , yellow fever virus claim 1 , dengue virus claim 1 , rhinovirus claim 1 , polio virus claim 1 , hepatitis A virus claim 1 , bovine viral diarrhea virus or Japanese encephalitis virus.6. A use of the compound of in the manufacture of a medicament for the treatment of any condition the result of an infection by hepatitis C virus claim 2 , West Nile virus claim 2 , yellow fever virus claim 2 , dengue virus claim 2 , rhinovirus claim 2 , polio virus claim 2 , hepatitis A virus claim 2 , bovine viral diarrhea virus or Japanese encephalitis virus.7. A method of treatment in a subject in need thereof claim 2 , which comprises:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering a therapeutically effective amount of the compound of to the subject.'}8. A method of treatment in a subject in need thereof claim 2 , which comprises:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'administering a therapeutically effective amount of the compound of to the subject.'}11. A ...

Nucleoside phosphoramidates

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

ANTIVIRAL COMPOUNDS INHIBITORS OF HCV NS5A

CONDENSED IMIDAZOLYLIMIDAZOLES AS ANTIVIRAL COMPOUNDS

Nucleoside phosphoramidates

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.

Synthesis of purine nucleosides

A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Methods and compositions for treating hepatitis c virus

Disclosed herein is a method of treating a subject infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period. Also disclosed herein is a composition useful for the treatment of hepatitis C virus infection, said composition comprising an effective amount of GS-7977 and an effective amount of ribavirin.

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. 181.-. (canceled)83. The compound according to claim 82 , wherein the compound is at least 98% of the Sstereoisomer represented by the formula (S-4) and not more than 2% of the Rstereoisomer represented by the formula (R-4).84. The compound according to claim 82 , wherein the compound is at least 99% of the Sstereoisomer represented by the formula (S-4) and not more than 1% of the Rstereoisomer represented by the formula (R-4).85. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.86. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.87. A pharmaceutical composition comprising the compound according to and a pharmaceutically acceptable medium.88. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .89. The method according to further comprising administering to the human another antiviral agent.90. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .91. The method according to further comprising administering to the human another antiviral agent.92. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to .93. The method according to further comprising administering to the human another antiviral agent. The right of priority is claimed to U.S. Provisional Patent Application Nos. 61/179,923, filed May 20, 2009, and 61/319,513, filed Mar. 31, 2010, the subject matter ...

NUCLEOSIDE PHOSPHORAMIDATES

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. 181.-. (canceled)83. The compound according to claim 82 , wherein LG′ is p-nitrophenoxide claim 82 , p-chlorophenoxide claim 82 , o-chlorophenoxide claim 82 , 2 claim 82 ,4-dinitrophenoxide claim 82 , or pentafluorophenoxide.84. The compound according to claim 82 , wherein LG′ is p-nitrophenoxide.85. The compound according to claim 82 , wherein LG′ is p-chlorophenoxide.86. The compound according to claim 82 , wherein LG′ is o-chlorophenoxide.87. The compound according to claim 82 , wherein LG′ is pentafluorophenoxide.88. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'sup': i', 'i, 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with isopropyl-alanate and a first base to obtain (LG′)P(O)(LG)(NHAla-Pr), followed by reacting (LG′)P(O)(LG)(NHAla-Pr) with phenol and a second base.'}89. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with phenol and a first base to obtain (LG′)P(O)(LG)(OPh), followed by reacting (LG′)P(O)(LG)(OPh) with isopropyl-alanate and a second base.'}90. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'reacting (LG′)P(O)(LG), wherein LG and LG′ are independently leaving groups, with a combination of isopropyl-alanate, phenol, and at least one base.'}91. A process for preparing the compound according to claim 82 , which comprises:{'sub': '2', 'sup': i', 'i, 'reacting (PhO)P(O)(LG), wherein LG and LG′ are independently leaving groups, with isopropyl-alanate and a first base to obtain (PhO)P(O)(LG)(NHAla-Pr), ...

NUCLEOSIDE PHOSPHORAMIDATES

A nucleoside compound having activity against hepatitis C virus is disclosed. 2. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .3. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus claim 1 , West Nile virus claim 1 , yellow fever virus claim 1 , dengue virus claim 1 , rhinovirus claim 1 , polio virus claim 1 , hepatitis A virus claim 1 , bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to .4. The method of treatment according to wherein the subject is infected with hepatitis C virus.5. A method of treatment in a subject in need thereof claim 1 , which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to .7. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .8. A method of treatment of a subject infected with a virus selected from the group consisting of hepatitis C virus claim 6 , West Nile virus claim 6 , yellow fever virus claim 6 , dengue virus claim 6 , rhinovirus claim 6 , polio virus claim 6 , hepatitis A virus claim 6 , bovine viral diarrhea virus or Japanese encephalitis virus which comprises administering to the subject a therapeutically effective amount of the compound according to .9. The method of treatment according to wherein the subject is infected with hepatitis C virus.10. A method of treatment in a subject in need thereof claim 6 , which comprises contacting at least one hepatitis C virus infected cell with at least one compound according to .11. The compound of wherein Ris OMe.12. The compound of wherein Ris OH.13. A pharmaceutical composition comprising a pharmaceutically acceptable medium and the compound according to .14. A pharmaceutical composition comprising a pharmaceutically acceptable medium and ...

Methods for treating hcv

This invention folates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions,

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment uses, and processes for preparing each of which utilize the compound represented by formula I.

Compounds

Disclosed herein are 2′-spiro-nucleosides and derivatives thereof useful for treating a subject infected by hepatitis C virus or dengue virus.

Solid dispersion formulation of an antiviral compound

Disclosed are solid dispersions comprising a compound having the formula: wherein the compound is dispersed within a polymer matrix formed by a pharmaceutically acceptable polymer, and further wherein the compound is substantially amorphous. Also disclosed are pharmaceutical compositions comprising the compound and methods of use for the compound.

NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: 112-. (canceled)14. The compound according to claim 13 , wherein:{'sup': '1', 'Ris hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;'}{'sup': '3a', 'Ris H; and'}{'sup': '3b', 'sub': 3', '3', '2', '2', '3', '2', '3', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2, 'Ris H, CH, CH(CH), CHCH(CH), CH(CH)CHCH, CHPh, CH-indol-3-yl, —CHCHSCH, CHCOH, CHC(O)NH, CHCHCOOH, CHCHC(O)NH, CHCHCHCHNH, —CHCHCHNHC(NH)NH, CH-imidazol-4-yl, CHOH, CH(OH)CH, CH((4′-OH)-Ph), CHSH, or lower cycloalkyl.'}15. The compound according to claim 13 , wherein:{'sup': '1', 'Ris hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;'}{'sup': '3a', 'Ris H;'}{'sup': '3b', 'sub': 3', '3', '2', '2', '3', '2', '3', '2', '3', '2, 'Ris H, CH, CH(CH), CHCH(CH), CH(CH)CHCH, CHPh, or lower cycloalkyl; and'}{'sup': 7', '8, 'sub': 3', '3', '3-q', 'q', '2', '3', '2', '3', '3', '2, 'Rand Rare independently H, F, Br, SCH, CH, CHX, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, COCH, CONH, CONHCH, or CON(CH).'}16. The compound according to claim 13 , wherein:{'sup': '1', 'Ris hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3a', 'Ris H;'}{'sup': '3b', 'sub': 3', '3', '2', '2', '3', '2', '3', '2', '3', '2, 'Ris H, CH, CH(CH), CHCH(CH), CH(CH)CHCH, CHPh, or lower cycloalkyl; and'}{'sup': 7', '8, 'sub': 3', '3', '3-q', 'q', '2', '3', '2', '3', '3', '2, 'Rand Rare independently H, F, Br, SCH, CH, CHX, where X is F, Cl, Br, ...

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions having an effective amount of substantially amorphous ledipasvir and an effective amount of substantially crystalline sofosbuvir.

Solid forms of an antiviral compound

Amorphous and crystalline solid forms of the anti-HCV compound (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the amorphous and crystalline forms.

ANTIVIRAL COMPOUNDS

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds. 127.-. (canceled)29. The composition of claim 28 , wherein the NS3 protease inhibitor is boceprevir.30. The composition of claim 28 , wherein the NS3 protease inhibitor is telaprevir.31. The composition of claim 28 , wherein the NS3 protease inhibitor is TMC435350.32. The composition of claim 28 , wherein the NS3 protease inhibitor is BI-1335.33. The composition of claim 28 , wherein the NS3 protease inhibitor is BI-1230.34. The composition of claim 28 , wherein the NS3 protease inhibitor is MK-7009.35. The composition of claim 28 , wherein the NS3 protease inhibitor is VBY-376.36. The composition of claim 28 , wherein the NS3 protease inhibitor is ITMN-191.38. The method of claim 37 , wherein the NS3 protease inhibitor is boceprevir.39. The method of claim 37 , wherein the NS3 protease inhibitor is telaprevir.40. The method of claim 37 , wherein the NS3 protease inhibitor is TMC435350.41. The method of claim 37 , wherein the NS3 protease inhibitor is BI-1335.42. The method of claim 37 , wherein the NS3 protease inhibitor is BI-1230.43. The method of claim 37 , wherein the NS3 protease inhibitor is MK-7009.44. The method of claim 37 , wherein the NS3 protease inhibitor is VBY-376.45. The method of claim 37 , wherein the NS3 protease inhibitor is ITMN-191.46. The method of claim 37 , wherein the human is treated for 12 weeks or less.47. The method of claim 37 , wherein the human is treated for 8 weeks or less.48. The method of claim 37 , wherein the human is treated for 6 weeks or less.49. The method of claim 37 , wherein the human is treated for 4 weeks or less.50. The method of claim 37 , wherein the human is treated for 2 weeks or less. This application claims priority to U.S. Provisional Application Nos. 61/177,972, filed ...

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions having an effective amount of substantially amorphous ledipasvir and an effective amount of substantially crystalline sofosbuvir.

NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: 13.-. (canceled)9. A pharmaceutical formulation comprising a compound of and a pharmaceutically acceptable excipient.101. A method of treating HCV comprising administering a therapeutically effective amount of a compound of claim to a human subject in need thereof.11. The method of further comprising administering to the subject a therapeutically effective amount of another antiviral agent.12. The methods of claim 11 , wherein the another antiviral agent is an NS5A inhibitor.13. The methods of claim 11 , wherein the another antiviral agent is an NS3 inhibitor.14. The method of claim 13 , further comprising administering to the subject a therapeutically effective amount of an NS5A inhibitor. The present invention pertains to nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. The invention provides novel chemical compounds, and the use of these compounds alone or in combination with other antiviral agents for treating HCV infection.Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population. There are an estimated 4.5 million infected people in the United States alone, according to the U.S. Center for Disease Control. According to the World Health Organization, there are more than 200 million infected individuals worldwide, with at least 3 to 4 million people being infected ...

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

PREPARATION OF 2'-FLUORO-2'-ALKYL-SUBSTITUTED OR OTHER OPTIONALLY SUBSTITUTED RIBOFURANOSYL PYRIMIDINES AND PURINES AND THEIR DERIVATIVES

The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside. 8. The compound of claim 7 , wherein Ris H and Ris methyl. This application is a continuation of U.S. patent application Ser. No. 14/808,147, filed Jul. 24, 2015, which is a divisional of Ser. No. 13/917,173, filed Jun. 13, 2013, which is a continuation of U.S. patent application Ser. No. 11/225,425, filed Sep. 13, 2005, which claims the benefit of Provisional Patent Application Ser. No. 60/609,783, filed Sep. 14, 2004, Provisional Patent Application Ser. No. 60/610,035, filed Sep. 15, 2004, and Provisional Patent Application Ser. No. 60/666,230, filed Mar. 29, 2005. The entire contents of all of the above-mentioned applications are incorporated herein by reference.The present invention provides (i) processes for preparing a 2-deoxy-2-fluoro-2-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.HCV infection has reached epidemic levels worldwide, and has tragic effects on the infected patients. Presently there is no effective treatment for this infection and the only drugs available for treatment of chronic hepatitis C are various forms of alpha interferon (IFN-α), either alone or in combination with ribavirin. However, the therapeutic value of these treatments has been compromised largely due to adverse effects, which highlights the need for development of additional options ...

METHODS OF PREVENTING AND TREATING RECURRENCE OF A HEPATITIS C VIRUS INFECTION IN A SUBJECT AFTER THE SUBJECT HAS RECEIVED A LIVER TRANSPLANT

This application describes methods of preventing, treating or reducing the risk of recurrence of a hepatitis C virus infection in a subject after the subject has received a liver transplant. Disclosed herein are methods of preventing or reducing the risk of recurrence of a hepatitis C virus infection in a subject after the subject has received a liver transplant, the methods comprising administering to the subject an effective amount of Compound 1. 1. A method of preventing or reducing the risk of post-liver transplant recurrence of a hepatitis C virus infection comprising administering to a subject an effective amount of Compound 1.2. The method of claim 1 , wherein Compound 1 is administered for a pre-transplant duration claim 1 , wherein the pre-transplant duration is from about 1 week to about 48 weeks.3. The method of claim 1 , wherein Compound 1 is administered for a post-transplant duration claim 1 , wherein the post-transplant duration is from about 1 week to about 48 weeks.4. The method of claim 1 , further comprising administering to the subject an effective amount of ribavirin claim 1 , wherein the effective amount of Compound 1 is about 400 mg per day and the effective amount of ribavirin is from about 1000 mg to about 1200 mg per day.5. A method of preventing or reducing the risk of post-liver transplant recurrence of a hepatitis C virus infection comprising providing to a subject a 5′-mono- claim 1 , di- or triphosphate metabolite of Compound 1.6. A method of reducing HCV RNA levels to lower than about 25 IU/mL in a subject having received a liver transplant comprising administering to the subject an effective amount of Compound 1.7. The method of claim 6 , wherein the effective amount of Compound 1 is administered for a pre-transplant duration claim 6 , wherein the pre-transplant duration is from about 1 week to about 48 weeks.8. The method of claim 7 , wherein the pre-transplant duration is from about 12 weeks to about 48 weeks.9. The method of claim ...

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Methods for treating hcv

This invention relates to combinations of therapeutic molecules useful for treating hepatitis C virus infection. The present invention relates to methods, uses, dosing regimens, and compositions.

Processes for preparing antiviral compounds

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

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.

Modified fluorinated nucleoside analogues

The disclosed invention provides compositions and methods of treating a Flaviviridae infection, including hepatitis C virus, West Nile Virus, yellow fever virus, and a rhinovirus infection in a host, including animals, and especially humans, using a (2′R)-2′-deoxy-2′-fluoro-2′-C-methyl nucleosides, or a pharmaceutically acceptable salt or prodrug thereof.

Crystalline (S) -isopropyl 2 - (((S) - (((2R, 3R, 4R, 5R) -5- (2,4-dioxo-3,4-DIHYDROPYRIMIDIN- 1- (2 H) -yl) - 4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl) methoxy) (phenoxy) phosphoryl) amino) propanoate

Tablet comprising crystalline (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin-1 (2h)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate

Compounds

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

5 The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds. C:\pof\temp\SPEC-966759.docx

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions comprising Compound I, having the formula: and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Compositions and methods for treating hepatitis C virus

Disclosed herein are a composition and unit dosage form for the treatment of hepatitis C virus (HCV) infection comprising GS-7977 and at least one pharmaceutically acceptable excipient, as well as methods for making said composition and unit dosage form. Also disclosed herein is a method of treating a subject, preferably a human, infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds of formula (Ic): E-V-Z-P-M-A-A-M-P-Z-V-E (Ic) or a pharmaceutically acceptable salt thereof, wherein: each E is methoxycarbonylamino; each V is V 0 ; each Z is -C(=O)-; each P is each M is independently imidazolyl or benzimidazolyl; compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention provides a pharmaceutical composition comprising: (1) a compound of the formula: or a pharmaceutically acceptable salt thereof; (2) a NS5B polymerase inhibitor; and (3) a NS3 protease inhibitor; and relates to the use of (1), (2) and (3), in combination, in the prophylactic or therapeutic treatment of hepatitis C or a hepatitis C associated disorder.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds of formula compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds

The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Combination formulation of two antiviral compounds

Disclosed are pharmaceutical compositions comprising Compound I, having the formula:and an effective amount of sofosbuvir wherein the sofosbuvir is substantially crystalline. Also disclosed are methods of use for the pharmaceutical composition.

Condensed imidazolylimidazoles as antiviral compounds

9-(1h-imidazol-5-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazole derivatives and their use as inhibitors of hcv ns5a

The disclosure is related to anti-viral compounds of formula (I)         E 1a- V 1a -C(=O)-P 1a -W 1a -P 1b -C(=O)-V 1b -E 1b      (I) wherein W 1a is wherein Y 5 is -CH 2 -O- or -C(=O)-O-; X 5 is -CH=CH-; and W 1a is optionally substituted with halo or alkyl; and to compositions containing such compounds for use in the prophylactic or therapeutic treatment of hepatitis C.

Antiviral compounds

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Antiviral compounds based on condensed imidazolyl-dihydroisochromeno-naphthoimidazols

The invention relates to a specific group of novel antiviral compounds having a nucleus consisting of condensed imidazolyl-dihydroisochromeno-naphthoimidazoles.As typical representatives selected from this group can serve the following compounds:The claimed compounds may be useful for the treatment of hepatitis C virus infections.

Solid forms of an antiviral compound

Crystalline solid forms and the amorphous form of the anti-HCV compound 5-(3,3-dimethylbutyn-1-yl)-3-[(cis-4-hydroxy-4-{[(3S)-tetrahydrofuran-3-yloxy]methyl}cyclohexyl){[(1R)-4-methylcyclohex-3-en-1-yl]carbonyl}amino]thiophene-2-carboxylic acid (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.

Antiviral compounds

Antiviral compounds

Antiviral compounds

Antiviral compounds.

La presente invención se refiere a compuestos anti-virales, composiciones que contienen dichos compuestos, y métodos terapéuticos que incluyen la administración de dichos compuestos, así como a procesos e intermediarios útiles para preparar dichos compuestos.

Antiviral compounds

Anti-viral compounds

pharmaceutical composition comprising a combination of antiviral compounds and use of said compounds for the preparation of said composition

resumo patente de invenção: "compostos antivirais, seu uso e composição farmacêutica e combinação compreendendo os mesmos". a presente invenção refere-se a compostos antivirais, composições contendo tais compostos, e métodos terapêuticos que incluem a administração de tais compostos, bem como a processos e intermediários úteis para a preparação de tais compostos. summary patent of invention: "antiviral compounds, their use and pharmaceutical composition and combination comprising them". the present invention relates to antiviral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as processes and intermediates useful for the preparation of such compounds.

Antiviral compounds.

La presente invención se refiere a compuestos anti-virales, composiciones que contienen dichos compuestos, y métodos terapéuticos que incluyen la administración de dichos compuestos, así como a procesos e intermediarios útiles para preparar dichos compuestos.

antiviral compounds, their use and pharmaceutical composition comprising them

compostos antivirais, seu uso e composição farmacêutica compreendendo os mesmos. a presente invenção refere-se a compostos antivirais ou seus sais farmaceuticamente aceitáveis, composições compreendendo tais compostos, e o seu uso na preparação de uma composição farmacêutica para o tratamento ou prevenção de infecção por hcv em humano. antiviral compounds, their use and pharmaceutical composition comprising them. The present invention relates to antiviral compounds or pharmaceutically acceptable salts thereof, compositions comprising such compounds, and their use in the preparation of a pharmaceutical composition for the treatment or prevention of hcv infection in human.

Antiviral compounds

antiviral compounds, their use and pharmaceutical composition comprising the same

Antiviral compounds

Antiviral compounds

Un compuesto de fórmula:**Fórmula** o una sal farmacéuticamente aceptable del mismo. A compound of the formula: ** Formula ** or a pharmaceutically acceptable salt thereof.

Antiviral compounds.

La presente invención se refiere a compuestos anti-virales, composiciones que contienen dichos compuestos, y métodos terapéuticos que incluyen la administración de dichos compuestos, así como a procesos e intermediarios útiles para preparar dichos compuestos.

Compounds, pharmaceutical compositions comprising the same and uses thereof

Antiviral compounds

Antiviral compounds

Antiviral compounds

Antiviral compounds

Antiviral compounds

Antiviral compounds

Antiviral Compounds

Ledipasvir

Patent NL300796I2

Ledipasvir - extended SPC

Heteroaryl substituted benzimidazole derivative compounds; pharmaceutical composition comprising them; and its use in the treatment of hepatitis c.

COMPUESTOS DERIVADOS DE BENCIMIDAZOL HETEROARILO SUSTITUTIDO DE FORMULA: DONDE V, M, P Y L SON COMO SE DEFINEN EN LA MEMORIA DESCRIPTIVA Y PLIEGO; COMPOSICIÓN FARMACÉUTICA QUE LOS COMPRENDE; Y SU USO EN EL TRATAMIENTO DE LA HEPATITIS C. COMPOUNDS DERIVED FROM HETEROARYL BENZIMIDAZOLE SUBSTITUTE FORMULA: WHERE V, M, P AND L ARE AS DEFINED IN THE DESCRIPTIVE MEMORY AND SPECIFICATIONS; PHARMACEUTICAL COMPOSITION THAT INCLUDES THEM; AND ITS USE IN THE TREATMENT OF HEPATITIS C.

Anti-viral compounds

Η εφεύρεση σχετίζεται με αντι-ιικές ενώσεις, συνθέσεις που περιέχουν τέτοιες ενώσεις και θεραπευτικές μεθόδους που περιλαμβάνουν την χορήγηση τέτοιων ενώσεων, καθώς επίσης με μεθόδους και ενδιάμεσα χρήσιμα για παρασκευή τέτοιων ενώσεων. The invention relates to antiviral compounds, compositions containing such compounds, and therapeutic methods comprising administering such compounds, as well as methods and intermediates useful for the preparation of such compounds.