BIOMAT Database Logo BIOMAT Database Logo

Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs. 2018

Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
School of Pharmacy and Pharmaceutical Sciences, Redwood building, King Edwards VII Avenue, CF10 3NB Cardiff, Wales, United Kingdom.

The importance of phosphonoamidate prodrugs (ProTides) of acyclic nucleoside phosphonate (ANPs) is highlighted by the approval of Tenofovir Alafenamide Fumarate for the treatment of HIV and HBV infections. In the present paper we are reporting an expedient, one-pot, two-steps synthesis of allyl phosphonoamidates and diamidates that offers a time saving strategy when compared to literature methods. The use of these substrates in the cross metathesis reactions with alkenyl functionalised thymine and uracil nucleobases is reported. ANPs prodrugs synthesized via this methodology were evaluated for their antiviral activities against DNA and RNA viruses. It is anticipated that the use of 5,6,7,8-tetrahydro-1-napthyl as aryloxy moiety is capable to confer antiviral activity among a series of otherwise inactive uracil ProTides.

UI MeSH Term Description Entries
D009705 Nucleosides Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleoside,Nucleoside Analog,Nucleoside Analogs,Analog, Nucleoside,Analogs, Nucleoside
D011355 Prodrugs A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug. Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004267 DNA Viruses Viruses whose nucleic acid is DNA. DNA Virus,Virus, DNA,Viruses, DNA
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D012328 RNA Viruses Viruses whose genetic material is RNA. RNA Rodent Viruses,RNA Rodent Virus,RNA Virus,Rodent Virus, RNA,Rodent Viruses, RNA,Virus, RNA,Virus, RNA Rodent,Viruses, RNA,Viruses, RNA Rodent
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D063065 Organophosphonates Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P Phosphonate,Phosphonates,Phosphonic Acid Esters,Acid Esters, Phosphonic,Esters, Phosphonic Acid

Related Publications

Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Synthesis of nucleoside phosphate and phosphonate prodrugs.
September 2014, Chemical reviews,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Synthesis and biological evaluation of acyclic phosphonic acid nucleoside derivatives.
January 2013, Nucleosides, nucleotides & nucleic acids,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
New cycloAmb-nucleoside phosphonate prodrugs.
January 2007, Nucleosides, nucleotides & nucleic acids,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases.
September 2015, Bioorganic & medicinal chemistry,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.
September 2017, Bioorganic & medicinal chemistry,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Synthesis and Anti-HIV Activity of Guanine Modified Fluorinated Acyclic Nucleoside Phosphonate Derivatives.
February 2019, Chemistry & biodiversity,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Synthesis and biological effects of acyclic pyrimidine nucleoside analogues.
September 1981, Journal of medicinal chemistry,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Antiviral acyclic nucleoside phosphonate analogues as inhibitors of purine nucleoside phosphorylase.
January 1998, Advances in experimental medicine and biology,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
Synthesis and biological studies of novel nucleoside phosphoramidate prodrugs.
December 2001, Journal of medicinal chemistry,
Elisa Pileggi, and Michaela Serpi, and Graciela Andrei, and Dominique Schols, and Robert Snoeck, and Fabrizio Pertusati
A novel and efficient one-pot synthesis of symmetrical diamide (bis-amidate) prodrugs of acyclic nucleoside phosphonates and evaluation of their biological activities.
September 2011, European journal of medicinal chemistry,
Copied contents to your clipboard!