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

  • Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):635-40. doi: 10.1080/15257770701490472.
Alan X Xiang  1 ,  Stephen E Webber ,  Bradley M Kerr ,  Erik J Rueden ,  Joseph R Lennox ,  Gregory J Haley ,  Tingmin Wang ,  John S Ng ,  Mark R Herbert ,  David L Clark ,  Virginia N Banh ,  Wei Li ,  Simon P Fletcher ,  Kevin R Steffy ,  Darian M Bartkowski ,  Leonid I Kirkovsky ,  Lisa A Bauman ,  Devron R Averett
Affiliations
PMID: 18066870 DOI: 10.1080/15257770701490472
Abstract

ANA975, a 5-amino-3-beta -D-ribofuranosyl-3H-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 and effective, delivering levels of isatoribine that have been shown to be clinically relevant.

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