Tyrosine-based prodrugs of acyclic nucleoside phosphonates

0428927 - ÚOCHB 2015 CZ eng C - Conference Paper (international conference)
Tichý, Tomáš - Pomeisl, Karel - Krečmerová, Marcela - McKenna, Ch. E.
Tyrosine-based prodrugs of acyclic nucleoside phosphonates.
Chemistry of Nucleic Acid Components. 16th Symposium. Praha: Institute of Organic Chemistry and Biochemistry AS CR, v. v. i, 2014 - (Hocek, M.), s. 126-128. Collection Symposium Series, 14. ISBN 978-80-86241-50-0.
[Symposium on Chemistry of Nucleic Acid Components /16./. Český Krumlov (CZ), 08.06.2014-13.06.2014]
R&D Projects: GA ČR(CZ) GA14-00522S
Institutional support: RVO:61388963
Keywords : acyclic nucleoside phosphonates * prodrug * tyrosine
Subject RIV: CC - Organic Chemistry

Prodrug approach based on masking of a phosphonate function by ester linkage to a tyrosine promoiety has been developed. Results demonstrate that tyrosine is a promoiety providing drug conjugates with good chemical stability, bioavailability and efficient activation to active drug species. Another properties like metabolic stability and antiviral activity can be tuned by modification of the carboxyl function of the promoiety. Phosphonate monoester prodrugs were prepared by PyBOP coupling of a protected tyrosine promoiety with suitably derivatized phosphonate function of the parent drug. Phosphonate diester prodrugs were prepared by "synthon" approach, emloying alkylation of purine nucleobase with pre-prepared PME synthons bearing two protected tyrosine promoieties.
Permanent Link: http://hdl.handle.net/11104/0234282