443642-29-3Relevant articles and documents
NUCLEOSIDE DERIVATIVES AS INHIBITORS OF RNA-DEPENDENT RNA VIRAL POLYERMASE
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Paragraph 0786; 0787; 0788; 0789, (2017/07/14)
The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.
NEW ANTIVIRAL MODIFIED NUCLEOSIDES
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Page/Page column 82, (2010/04/03)
This invention relates to novel compounds that have various medicinal applications, e.g. for the treatment and/or prevention of viral infections.
TRICYCLIC-NUCLEOSIDE COMPOUNDS FOR TREATING VIRAL INFECTIONS
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Page/Page column 45, (2009/03/07)
Disclosed are tricyclic nucleoside compounds of formula (I), and methods thereof for treating viral infections mediated at least in part by a Flaviviridae family virus.
5-nitro-nucleoside compounds for treating viral infections
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Page/Page column 17, (2010/11/08)
Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus.
Practical synthesis of a potent hepatitis C virus RNA replication inhibitor
Bio, Matthew M.,Xu, Feng,Waters, Marjorie,Williams, J. Michael,Savary, Kimberly A.,Cowden, Cameron J.,Yang, Chunhua,Buck, Elizabeth,Song, Zhiguo J.,Tschaen, David M.,Volante,Reamer, Robert A.,Grabowski, Edward J. J.
, p. 6257 - 6266 (2007/10/03)
A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.
Structure - activity relationship of heterobase-modified 2′-C-methyl ribonucleosides as inhibitors of hepatitis C virus RNA replication
Eldrup, Anne B.,Prhavc, Marija,Brooks, Jennifer,Bhat, Balkrishen,Prakash, Thazha P.,Song, Quanlai,Bera, Sanjib,Bhat, Neelima,Dande, Prasad,Cook, P. Dan,Bennett, C. Frank,Carroll, Steven S.,Ball, Richard G.,Bosserman, Michele,Burlein, Christine,Colwell, Lawrence F.,Fay, John F.,Flores, Osvaldo A.,Getty, Krista,LaFemina, Robert L.,Leone, Joseph,MacCoss, Malcolm,McMasters, Daniel R.,Tomassini, Joanne E.,Von Langen, Derek,Wolanski, Bohdan,Olsen, David B.
, p. 5284 - 5297 (2007/10/03)
Hepatitis C virus infection constitutes a significant health problem in need of more effective therapies. We have recently identified 2′-C-methyladenosine and 2′-C-methylguanosine as potent nucleoside inhibitors of HCV RNA replication in vitro. However, both of these compounds suffered from significant limitations. 2′-C-Methyladenosine was found to be susceptible to enzymatic conversions by adenosine deaminase and purine nucleoside phosphorylase, and it displayed limited oral bioavailability in the rat. 2′-C-Methylguanosine, on the other hand, was neither efficiently taken up in cells nor phosphorylated well. As part of an attempt to address these limitations, we now report upon the synthesis and evaluation of a series of heterobase-modified 2′-C-methyl ribonucleosides. The structure-activity relationship within this series of nucleosides reveals 4-amino-7-(2-C-methyl- β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5-fluoro-7-(2-C- methyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine as potent and noncytotoxic inhibitors of HCV RNA replication. Both 4-amino-7-(2-C-methyl- β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 4-amino-5-fluoro-7-(2-C- methyl-β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine display improved enzymatic stability profiles as compared to that of 2′-C-methyladenosine. Consistent with these observations, the most potent compound, 4-amino-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine ribonucleoside, is orally bioavailable in the rat. Together, the potency of the 2′-C-methyl-4-amino- pyrrolo[2,3-d]pyrimidine ribonucleosides and their improved pharmacokinetic properties relative to that of 2′-C-methyladenosine suggests that this class of compounds may have clinical utility.
Inhibiting Coronaviridae viral replication and treating Coronaviridae viral infection with nucleoside compounds
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Page/Page column 14, (2010/02/09)
Infection by a Coronaviridae virus (e.g., a coronavirus) and/or illness due to a Coronaviridae virus are treated or protected against by administration of a therapeutically or prophylactically effective amount of certain nucleoside compounds and derivatives thereof, either alone or in a composition comprising the nucleoside compound or its derivative and a pharmaceutically acceptable carrier. In addition, replication of a Coronaviridae virus is inhibited by administration of the nucleoside compounds and derivatives thereof, either alone or in pharmaceutical compositions. The nucleosides are particularly suitable for use in treating or prophylaxis of an infection by the SARS virus and/or in treating or prophylaxis of SARS, and for use in inhibiting replication of the SARS virus. The nucleoside compounds and derivatives can optionally be administered in combination with other agents active against the Coronaviridae virus and/or an illness due to the virus. The nucleoside compounds are also for use in the manufacture of medicaments for the inhibition of Coronaviridae virus replication, for the treatment or prophylaxis of Coronaviridae virus infection, and/or for the treatment or prophylaxis of an illness due to a Coronaviridae virus (e.g., the SARS virus). In addition, the compounds are for use as medicaments for the inhibition of Coronaviridae virus replication, for the treatment or prophylaxis of Coronaviridae virus infection, and/or for the treatment or prophylaxis of an illness due to a Coronaviridae virus.
Oligonucleotides having modified nucleoside units
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, (2008/06/13)
Disclosed are oligonucleotide that include one or more modified nucleoside units. The oligonucleotides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
Oligonucleotides having modified nucleoside units
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, (2008/06/13)
Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
OLIGONUCLEOTIDES HAVING MODIFIED NUCLEOSIDE UNITS
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Page 156-157, (2010/02/04)
Disclosed are oligonucleotides and oligonucleosides that include one or more modified nucleoside units. The oligonucleotides and oligonucleosides are particularly useful as antisense agents, ribozymes, aptamer, siRNA agents, probes and primers or, when hybridized to an RNA, as a substrate for RNA cleaving enzymes including RNase H and dsRNase.
