Stereoselective synthesis and biological evaluations of novel 3'-deoxy-4'-azaribonucleosides as inhibitors of hepatitis C virus RNA replication.
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
Ugo
U
Dipartimento di Scienze Chimiche, Universita di Catania, Catania 95125, Italy. uchiacchio@unict.it.
Borrello
Luisa
L
Crispino
Lia
L
Rescifina
Antonio
A
Merino
Pedro
P
Macchi
Beatrice
B
Balestrieri
Emanuela
E
Mastino
Antonio
A
Piperno
Anna
A
Romeo
Giovanni
G
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D011392:Proline / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology; D012367:RNA, Viral / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D003853:Deoxyribonucleosides; D011392:Proline; D011759:Pyrrolidines; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase