3'-Deoxy-4'-azaribonucleosides (15a-d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-L-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that synthesized pyrrolidine nucleosides represent a new template for antiviral or other biological studies and could be considered for novel combination therapy against HCV infection using nucleoside inhibitors and non-nucleoside inhibitors of HCV NS5B.

Chiacchio, U., Borrello, L., Crispino, L., Rescifina, A., Merino, P., Macchi, B., et al. (2009). Stereoselective Synthesis and Biological Evaluations of Novel 3 '-Deoxy-4 '-azaribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication. JOURNAL OF MEDICINAL CHEMISTRY, 52(13), 4054-4057 [10.1021/jm900197j].

Stereoselective Synthesis and Biological Evaluations of Novel 3 '-Deoxy-4 '-azaribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication

MACCHI, BEATRICE;BALESTRIERI, EMANUELA;
2009-01-01

Abstract

3'-Deoxy-4'-azaribonucleosides (15a-d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-L-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that synthesized pyrrolidine nucleosides represent a new template for antiviral or other biological studies and could be considered for novel combination therapy against HCV infection using nucleoside inhibitors and non-nucleoside inhibitors of HCV NS5B.
2009
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
Settore CHIM/06 - CHIMICA ORGANICA
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
antivirus agent; ethyl 2 [5 fluoro 2,4 dioxo 3,4 dihydropyrimidin 1(2h) yl] 3 hydroxy 5 (hydroxymethyl)pyrrolidine 1 carboxylate; interferon; tert butyl 2 [2,4 dioxo 3,4 dihydropyrimidin 1(2h) yl] 3 hydroxy 5 (hydroxymethyl)pyrrolidine 1 carboxylate; tert butyl 2 [4 amino 2 oxopyrimidin 1(2h) yl] 3 hydroxy 5 (hydroxymethyl)pyrrolidine 1 carboxylate; tert butyl 2 [5 fluoro 2,4 dioxo 3,4 dihydropyrimidin 1(2h) yl] 3 hydroxy 5 (hydroxymethyl)pyrrolidine 1 carboxylate; tert butyl 3 hydroxy 5 (hydroxymethyl) 2 [5 methyl 2,4 dioxo 3,4 dihydropyrimidin 1(2h) yl]pyrrolidine 1 carboxylate; unclassified drug; virus RNA; antiviral activity; article; controlled study; drug structure; drug synthesis; Hepatitis C virus; human; human cell; nonhuman; replicon; RNA replication; stereochemistry; Antiviral Agents; Deoxyribonucleosides; Hepacivirus; Humans; Proline; Pyrrolidines; RNA, Viral; Stereoisomerism; Viral Nonstructural Proteins; Virus Replication
Chiacchio, U., Borrello, L., Crispino, L., Rescifina, A., Merino, P., Macchi, B., et al. (2009). Stereoselective Synthesis and Biological Evaluations of Novel 3 '-Deoxy-4 '-azaribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication. JOURNAL OF MEDICINAL CHEMISTRY, 52(13), 4054-4057 [10.1021/jm900197j].
Chiacchio, U; Borrello, L; Crispino, L; Rescifina, A; Merino, P; Macchi, B; Balestrieri, E; Mastino, A; Piperno, A; Romeo, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39063
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