Synthesis and biological properties of prodrugs of (S)-3-(adenin-9-yl)-2-(phosphonomethoxy)propanoic acid

0458700 - ÚOCHB 2017 RIV FR eng J - Journal Article
Kaiser, Martin Maxmilian - Poštová Slavětínská, Lenka - Dračínský, Martin - Lee, Y. J. - Tian, Y. - Janeba, Zlatko
Synthesis and biological properties of prodrugs of (S)-3-(adenin-9-yl)-2-(phosphonomethoxy)propanoic acid.
European Journal of Medicinal Chemistry. Roč. 108, Jan 27 (2016), s. 374-380. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MV VG20102015046
Institutional support: RVO:61388963
Keywords : acyclic nucleoside phosphonates * (S)-CPMEA * antiviral * HCV * prodrugs
Subject RIV: CC - Organic Chemistry
Impact factor: 4.519, year: 2016

The lack of antiviral activity of recently described (S)-3-(adenin-9-yl)-2-(phosphonomethoxy)propanoic acid, or (S)-CPMEA in brief, has been speculated to possibly be due to the increased hydrophilicity of the molecule and, thus, by its limited cellular permeability. Efficient syntheses of novel lipophilic prodrugs of (S)-CPMEA masking either the carboxylic group or preferably both the phosphonate and carboxylic moieties, have been developed in order to increase bioavailability of the parent compound. Two prodrugs of (S)-CPMEA, namely phosphonate bis-amidate 15 and phenyloxy amidate 16, exhibited pan-genotypic anti-HCV activity at submicromolar concentrations.
Permanent Link: http://hdl.handle.net/11104/0258949