Journal ArticleDOI
Practical synthesis of a potent hepatitis C virus RNA replication inhibitor.
Matthew M. Bio,Feng Xu,Marjorie S. Waters,J. Michael Williams,Kimberly A. Savary,Cameron J. Cowden,Chunhua Yang,Elizabeth Buck,Zhiguo J. Song,David M. Tschaen,Ralph P. Volante,Robert A. Reamer,Edward J. J. Grabowski +12 more
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TLDR
A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described, which features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate.Abstract:
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.read more
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Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals
TL;DR: In this article, a review of coupling reagents for large-scale amide synthesis via the condensation of an acid and amine is presented, highlighting the benefits and drawbacks of each reagent on an industrial scale.
Patent
Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae infections
TL;DR: In this article, 2.2 and/or 3.2-branched nucleoside prodrugs of 1.2, 2.5, 3.5 and 4.5-branched nucleosides are described.
Journal ArticleDOI
Synthetic Entries to and Biological Activity of Pyrrolopyrimidines
TL;DR: This review summarizes recent literature on the synthesis and pharmaceutical properties of pyrrolopyrimidines and contains a description of common retro-synthetic strategies, with particular attention for newly reported synthetic entries to the scaffold.
Patent
2' and 3'-nucleoside prodrugs for treating flaviviridae infections
TL;DR: In this article, 2.2 and 3.5-prodrugs of 1′, 2′, 3′ or 4′-branched β-D or β-L nucleosides, or their pharmaceutically acceptable salts and derivatives are described, which are useful in the prevention and treatment of Flavivirus infections and other related conditions.
Patent
2-branched nucleosides and flaviviridae mutation
TL;DR: A method for the treatment of Flaviviridae infection that includes the administration of a 2-branched nucleoside, or a pharmaceutically acceptable prodrug and/or salt thereof, to a human in need of therapy in combination or alternation with a drug that directly or indirectly induces a mutation in the viral genome at a location other than a mutation of a nucleotide that results in a change from serine to a different amino acid in the highly conserved consensus sequence, XRXSGXXXT, or is associated with such a mutation as discussed by the authors
References
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Journal ArticleDOI
Vaccines to prevent viral hepatitis
Stanley M. Lemon,David L. Thomas +1 more
TL;DR: At least five different viruses cause hepatitis in humans, and two — hepatitis A virus (HAV) and hepatitis E virus (HEV) — are nonenveloped RNA viruses that are spread predominantly by fecal–oral transmission and cause acute self-limited disease.
Journal ArticleDOI
A Short, Flexible Route toward 2‘-C-Branched Ribonucleosides
TL;DR: In this paper, a five-step synthesis of 2'C-branched ribonucleosides from commercially obtained 1,3,5-tri-O-benzoyl-α-d-ribofuranose (4) is described.
Journal ArticleDOI
Hepatitis C virus: current understanding and prospects for future therapies
Hugo R. Rosen,David R. Gretch +1 more
TL;DR: Treatment with interferon alpha (IFN-alpha) has been disappointing, but higher and more frequent doses, and combination therapies, including nucleoside analogs, might lead to improved suppression of HCV RNA levels.
Journal ArticleDOI
2'-C-Branched Ribonucleosides: Synthesis of the Phosphoramidite Derivatives of 2'-C-beta-Methylcytidine and Their Incorporation into Oligonucleotides.
TL;DR: Oligonucleotides containing 2'-C-beta-methylcytidine undergo base-catalyzed degradation analogous to natural RNA through solid-phase synthesis using phosphoramidite derivatives.
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