Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine

…, JR Lennox, GJ Haley, T Wang, JS Ng…

Index: Xiang, Alan X.; Webber, Stephen E.; Kerr, Bradley M.; Rueden, Erik J.; Lennox, Joseph R.; Haley, Gregory J.; Wang, Tingmin; Ng, John S.; Herbert, Mark R.; Clark, David L.; Banh, Virginia N.; Li, Wei; Fletcher, Simon P.; Steffy, Kevin R.; Bartkowski, Darian M.; Kirkovsky, Leonid I.; Bauman, Lisa A.; Averett, Devron R. Nucleosides, Nucleotides and Nucleic Acids, 2007 , vol. 26, # 6-7 p. 635 - 640

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Citation Number: 30

Abstract

ANA975, a 5-amino-3-β-D-ribofuranosyl-3 H-thiazolo [4, 5-d] pyrimidin-2-one derivative, was synthesized in the search of an oral prodrug of isatoribine, a small molecule toll-like receptor 7 (TLR-7) agonist. Several strategies were studied to enable the kilogram-scale synthesis of ANA975. Three general total syntheses are described. In the phase I clinical study of ANA975 against hepatitis C virus (HCV), conversion to isatoribine in plasma was rapid ...