637338-78-4Relevant articles and documents
A conformational mimetic approach for the synthesis of carbocyclic nucleosides as anti-HCV leads
Kasula, Mohan,Balaraju, Tuniki,Toyama, Massaki,Thiyagarajan, Anandarajan,Bal, Chandralata,Baba, Masanori,Sharon, Ashoke
supporting information, p. 1673 - 1680 (2013/10/21)
Computer-aided approaches coupled with medicinal chemistry were used to explore novel carbocyclic nucleosides as potential anti-hepatitisC virus (HCV) agents. Conformational analyses were carried out on 6-amino-1H-pyrazolo[3,4-d]pyrimidine (6-APP)-based carbocyclic nucleoside analogues, which were considered as nucleoside mimetics to act as HCV RNA-dependent RNA polymerase (RdRp) inhibitors. Structural insight gained from the modeling studies revealed the molecular basis behind these nucleoside mimetics. The rationally chosen 6-APP analogues were prepared and evaluated for anti-HCV activity. RdRp SiteMap analysis revealed the presence of a hydrophobic cavity near C7 of the nucleosides; introduction of bulkier substituents at this position enhanced their activity. Herein we report the identification of an iodinated compound with an EC50 value of 6.6μM as a preliminary anti-HCV lead.