| Literature DB >> 21050754 |
P Ganapati Reddy1, Donghui Bao, Wonsuk Chang, Byoung-Kwon Chun, Jinfa Du, Dhanapalan Nagarathnam, Suguna Rachakonda, Bruce S Ross, Hai-Ren Zhang, Shalini Bansal, Christine L Espiritu, Meg Keilman, Angela M Lam, Congrong Niu, Holly Micolochick Steuer, Phillip A Furman, Michael J Otto, Michael J Sofia.
Abstract
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).Entities:
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Year: 2010 PMID： 21050754 DOI： 10.1016/j.bmcl.2010.10.035
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823