BIOMAT Database Logo BIOMAT Database Logo

Versatile synthesis of oxime-containing acyclic nucleoside phosphonates--synthetic solutions and antiviral activity. 2015

Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia. solyev@gmail.com.

New oxime-containing acyclic nucleoside phosphonates 9-{2-[(phosphonomethyl)oximino]ethyl}adenine (1), -guanine (2) and 9-{2-[(phosphonomethyl)oximino]propyl}adenine (3) with wide spectrum activity against different types of viruses were synthesized. The key intermediate, diethyl aminooxymethylphosphonate, was obtained by the Mitsunobu reaction. Modified conditions for the by-product separation (without chromatography and distillation) allowed us to obtain 85% yield of the aminooxy intermediate. The impact of DBU and Cs2CO3 on the N(9)/N(7) product ratio for adenine and guanine alkylation was studied. A convenient procedure for aminooxy group detection was found. The synthesized phosphonates were tested and they appeared to display moderate activity against different types of viruses (HIV, herpes viruses in cell cultures, and hepatitis C virus in the replicon system) without toxicity up to 1000 μM.

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
D010091 Oximes Compounds that contain the radical R2C Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
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
D014777 Virus Diseases A general term for diseases caused by viruses. Viral Diseases,Viral Infections,Virus Infections,Disease, Viral,Disease, Virus,Diseases, Viral,Diseases, Virus,Infection, Viral,Infection, Virus,Infections, Viral,Infections, Virus,Viral Disease,Viral Infection,Virus Disease,Virus Infection
D014780 Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Animal Viruses,Zoophaginae,Animal Virus,Virus,Virus, Animal,Viruses, Animal
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

Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Antiviral acyclic nucleoside phosphonates structure activity studies.
September 2006, Antiviral research,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity.
September 2017, Bioorganic & medicinal chemistry,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Synthesis of acyclic nucleoside phosphonates.
October 2005, Current protocols in nucleic acid chemistry,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Cytostatic activity of antiviral acyclic nucleoside phosphonates in rodent lymphocytes.
November 2003, Toxicology and applied pharmacology,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Ester prodrugs of acyclic nucleoside thiophosphonates compared to phosphonates: synthesis, antiviral activity and decomposition study.
May 2013, European journal of medicinal chemistry,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Metabolic diversity and antiviral activities of acyclic nucleoside phosphonates.
April 1995, Molecular pharmacology,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Acyclic nucleoside phosphonates containing the amide bond.
January 2016, Monatshefte fur chemie,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Acyclic nucleoside phosphonates: a key class of antiviral drugs.
November 2005, Nature reviews. Drug discovery,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: efficient synthesis and antiviral activity.
August 2011, Bioorganic & medicinal chemistry,
Pavel N Solyev, and Maxim V Jasko, and Alla A Kleymenova, and Marina K Kukhanova, and Sergey N Kochetkov
Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety.
September 2012, European journal of medicinal chemistry,
Copied contents to your clipboard!