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2′-Deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: Discovery of PSI-352938

التفاصيل البيبلوغرافية
العنوان: 2′-Deoxy-2′-α-fluoro-2′-β-C-methyl 3′,5′-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: Discovery of PSI-352938
المؤلفون: Holly M. Micolochick Steuer, Donghui Bao, Wonsuk Chang, Bruce S. Ross, Angela M. Lam, Shalini Bansal, Dhanapalan Nagarathnam, Michael J. Otto, P. Ganapati Reddy, Meg Keilman, Byoung-Kwon Chun, Congrong Niu, Hai-Ren Zhang, Rachakonda Suguna, Christine Espiritu, Phillip A. Furman, Jinfa Du, Michael J. Sofia
المصدر: Bioorganic & Medicinal Chemistry Letters. 20:7376-7380
بيانات النشر: Elsevier BV, 2010.
سنة النشر: 2010
مصطلحات موضوعية: Stereochemistry, Clinical Biochemistry, Molecular Conformation, Administration, Oral, Pharmaceutical Science, Hepacivirus, Viral Nonstructural Proteins, Crystallography, X-Ray, Antiviral Agents, Biochemistry, Structure-Activity Relationship, Cell Line, Tumor, Drug Discovery, Animals, Humans, Structure–activity relationship, Prodrugs, Nucleotide, Enzyme Inhibitors, Molecular Biology, chemistry.chemical_classification, biology, Organic Chemistry, Nucleosides, Prodrug, Nucleotidyltransferase, In vitro, Cyclic P-Oxides, Rats, Enzyme, chemistry, Enzyme inhibitor, biology.protein, Molecular Medicine, Nucleotides, Cyclic, Nucleoside
الوصف: A series of novel 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs were synthesized and evaluated for their in vitro anti-HCV activity and safety. These prodrugs demonstrated a 10-100-fold greater potency than the parent nucleoside in a cell-based replicon assay due to higher cellular triphosphate levels. Our structure-activity relationship (SAR) studies provided compounds that gave high levels of active triphosphate in rat liver when administered orally to rats. These studies ultimately led to the selection of the clinical development candidate 24a (PSI-352938).
تدمد: 0960-894X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0894d7978cc2668811feded8aada3bad
https://doi.org/10.1016/j.bmcl.2010.10.035
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....0894d7978cc2668811feded8aada3bad
قاعدة البيانات: OpenAIRE
الوصف
تدمد:0960894X