ArticleJournal of medicinal chemistry2011
Tyrosine-based 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) prodrugs: synthesis, stability, antiviral activity, and in vivo transport studies.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The trial behind it
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Chiral-Modified Nucleoside Analogues: From Bioactivity to Therapeutic Applications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Novel derivatives of brincidofovir and (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine inhibit orthopoxviruses and human adenoviruses more potently than brincidofovir.Signal transduction and targeted therapy · 2025Article
- NPP-669, a Novel Broad-Spectrum Antiviral Therapeutic with Excellent Cellular Uptake, Antiviral Potency, Oral Bioavailability, Preclinical Efficacy, and a Promising Safety Margin.Molecular pharmaceutics · 2023Article
- Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.Frontiers in chemistry · 2022Review
- Overview of Biologically Active Nucleoside Phosphonates.Frontiers in chemistry · 2020Review
- Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.ACS medicinal chemistry letters · 2019Article
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
- Amidate Prodrugs of Cyclic 9-(ACS medicinal chemistry letters · 2018Article
- New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.Bioorganic & medicinal chemistry · 2017Article
- Sulfotyrosine dipeptide: Synthesis and evaluation as HIV-entry inhibitor.Bioorganic chemistry · 2016Article
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- Synthesis and biological evaluation of prodrugs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate.Bioorganic & medicinal chemistry letters · 2013Article
- Evolution of an amino acid based prodrug approach: stay tuned.Molecular pharmaceutics · 2013Article
- Structure of cyclic nucleoside phosphonate ester prodrugs: an inquiry.The Journal of organic chemistry · 2012Article
- Phosphoramidates and phosphonamidates (ProTides) with antiviral activity.Antiviral chemistry & chemotherapyReview
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC(50) values for the prodrugs (<0.1-50 μM) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those for the parent drugs ((S)-HPMPC, 2; (S)-HPMPA, 1; IC(50) 0.3-35 μM); there was no cytoxicity with KB or HFF cells at ≤100 μM. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (<30-1732 min) with differences of 3-10× between phostonate diastereomers. The tyrosine alkylamide derivatives of 3 and 4 were the most stable. (l)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs <5%).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.