Synthesis of new 2 ′-β- C-methyl related triciribine analogues as anti-HCV agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 13; pp. 3517 - 3520
• Main Authors: Smith, Kenneth L., Lai, Vicky C.H., Prigaro, Brett J., Ding, Yili, Gunic, Esmir, Girardet, Jean-Luc, Zhong, Weidong, Hong, Zhi, Lang, Stanley, An, Haoyun
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05.07.2004; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Cells, Cultured; Cytotoxicity Tests, Immunologic; Hepacivirus - drug effects; Hepacivirus - enzymology; Hepacivirus - physiology; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; Ribonucleosides - chemical synthesis; Ribonucleosides - pharmacology; Virus Replication - drug effects; Nitrogen heterocycle; Branched compound; Tricyclic compound; In vitro; Virus; Structure activity relation; Triciribine; Antiviral; Flaviviridae; Ribonucleoside; Chemical synthesis; Hepatitis C virus; Hepacivirus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.04.067

Ten new β- d-ribofuranosyl and 2 ′-β- C-methyl-β- d-ribofuranosyl triciribine derivatives 4– 13 were synthesized. HCV replicon studies of these compounds reveal some compounds possess interesting anti-HCV properties. Ten new β- d-ribofuranosyl and 2 ′-β- C-methyl-β- d-ribofuranosyl triciribine derivatives 4– 13 with various N4 and 6- N substituents on the tricyclic ring were synthesized from the corresponding toyocamycin and new 2 ′-β- C-methyl toyocamycin derivatives. The inhibitory studies of these compounds in the HCV replicon assay reveal that some of them possess interesting anti-HCV properties with low cytotoxicity.