scholarly journals Acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: Efficient synthesis and antiviral activity

2011 ◽  
Vol 19 (15) ◽  
pp. 4445-4453 ◽  
Author(s):  
Dana Hocková ◽  
Antonín Holý ◽  
Graciela Andrei ◽  
Robert Snoeck ◽  
Jan Balzarini
Keyword(s):  
Antiviral Activity ◽  
Efficient Synthesis ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

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

2015 ◽  
Vol 13 (44) ◽  
pp. 10946-10956
Author(s):  
Pavel N. Solyev ◽  
Maxim V. Jasko ◽  
Alla A. Kleymenova ◽  
Marina K. Kukhanova ◽  
Sergey N. Kochetkov
Keyword(s):  
Antiviral Activity ◽  
Wide Spectrum ◽  
Different Types ◽  
Acyclic Nucleoside Phosphonates ◽  
Spectrum Activity ◽  
Acyclic Nucleoside

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.

Novel and Efficient Synthesis of gem -Difluorinated Derivatives of Acyclic Nucleoside Phosphonates (ANPs)

2016 ◽  
Vol 1 (10) ◽  
pp. 2102-2106 ◽  
Author(s):  
Karel Pomeisl ◽  
Petr Beier ◽  
Radek Pohl ◽  
Marcela Krečmerová
Keyword(s):  
Efficient Synthesis ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Derivatives Of

scholarly journals New prodrugs of two pyrimidine acyclic nucleoside phosphonates: Synthesis and antiviral activity

2017 ◽  
Vol 25 (17) ◽  
pp. 4637-4648 ◽  
Author(s):  
Marcela Krečmerová ◽  
Martin Dračínský ◽  
Robert Snoeck ◽  
Jan Balzarini ◽  
Karel Pomeisl ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

New in vitro method for evaluating antiviral activity of acyclic nucleoside phosphonates against plant viruses

2010 ◽  
Vol 88 (3) ◽  
pp. 296-303 ◽  
Author(s):  
J. Špak ◽  
A. Holý ◽  
D. Pavingerová ◽  
I. Votruba ◽  
V. Špaková ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Plant Viruses ◽  
In Vitro Method ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

scholarly journals Inhibition of Herpesvirus Replication by Hexadecyloxypropyl Esters of Purine- and Pyrimidine-Based Phosphonomethoxyethyl Nucleoside Phosphonates

2008 ◽  
Vol 52 (12) ◽  
pp. 4326-4330 ◽  
Author(s):  
Mark N. Prichard ◽  
Caroll B. Hartline ◽  
Emma A. Harden ◽  
Shannon L. Daily ◽  
James R. Beadle ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Hiv Infections ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Ester Prodrugs

ABSTRACT Patients infected with human immunodeficiency virus (HIV) often suffer from herpesvirus infections as a result of immunosuppression. These infections can occur while patients are receiving antiretroviral therapy, and additional drugs required to treat their infection can adversely affect compliance. It would be useful to have antivirals with a broader spectrum of activity that included both HIV and the herpesviruses. We reported previously that alkoxyalkyl ester prodrugs of cidofovir are up to 3 orders of magnitude more active against herpesvirus replication and may be less toxic than the unmodified drug. To determine if this strategy would be effective for certain phosphonomethoxyethyl nucleoside phosphonates which are also active against HIV infections, the hexadecyloxypropyl (HDP) esters of 1-(phosphonomethoxyethyl)-cytosine, 1-(phosphonomethoxyethyl)-5-bromo-cytosine (PME-5BrC), 1-(phosphonomethoxyethyl)-5-fluoro-cytosine, 9-(phosphonomethoxyethyl)-2,6-diaminopurine (PME-DAP), and 9-(phosphonomethoxyethyl)-2-amino-6-cyclopropylaminopurine (PME-cPrDAP) were evaluated for activity against herpesvirus replication. The HDP esters were substantially more active than the unmodified acyclic nucleoside phosphonates, indicating that esterification with alkoxyalkyl groups increases the antiviral activity of many acyclic nucleoside phosphonates. The most interesting compounds included HDP-PME-cPrDAP and HDP-PME-DAP, which were 12- to 43-fold more active than the parent nucleoside phosphonates against herpes simplex virus and cytomegalovirus, and HDP-PME-cPrDAP and HDP-PME-5BrC which were especially active against Epstein-Barr virus. The results presented here indicate that HDP-esterified acyclic nucleoside phosphonates with antiviral activity against HIV also inhibit the replication of some herpesviruses and can extend the spectrum of activity for these compounds.

The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind–Srogl cross-coupling reaction

Tetrahedron ◽  
2011 ◽  
Vol 67 (38) ◽  
pp. 7379-7385 ◽  
Author(s):  
Petra Břehová ◽  
Michal Česnek ◽  
Martin Dračínský ◽  
Antonín Holý ◽  
Zlatko Janeba
Keyword(s):  
Coupling Reaction ◽  
Cross Coupling ◽  
Efficient Synthesis ◽  
Cross Coupling Reaction ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

Efficient synthesis and biological properties of the 2′-trifluoromethyl analogues of acyclic nucleosides and acyclic nucleoside phosphonates

2011 ◽  
Vol 76 (10) ◽  
pp. 1187-1198 ◽  
Author(s):  
Petr Jansa ◽  
Viktor Kolman ◽  
Alexandra Kostinová ◽  
Martin Dračínský ◽  
Helena Mertlíková-Kaiserová ◽  
...  
Keyword(s):  
Biological Properties ◽  
Trifluoromethyl Group ◽  
Efficient Synthesis ◽  
Phosphonic Acids ◽  
Acyclic Nucleosides ◽  
Acyclic Nucleoside Phosphonates ◽  
Dialkyl Phosphonates ◽  
Acyclic Nucleoside ◽  
High Yields ◽  
Very High

Efficient and optimized procedure for the preparation of several acyclic nucleosides and acyclic nucleoside phosphonates substituted at the C-2′ position of the aliphatic part by the trifluoromethyl group is described. Trifluoromethyloxirane was found to be an excellent reagent for the introduction of the 1,1,1-trifluoropropan-2-ol moiety. Surprisingly, the next reaction of these 1,1,1-trifluoropropan-2-ols with the reagent for the introduction of the methylphosphonic residue afforded the desired phosphonates in very high yields and finally a novel simple and scalable procedure for the isolation of free phosphonic acids, after the reaction of dialkyl phosphonates with bromotrimethylsilane, was developed. Prepared compounds were evaluated for their biological properties, but none of the prepared phosphonic acids or acyclic nucleosides exhibits any antiviral, antiproliferative or anti-toxin activities.

scholarly journals Antiviral Activities of Novel 5-Phosphono-Pent-2-en-1-yl Nucleosides and Their Alkoxyalkyl Phosphonoesters

2006 ◽  
Vol 51 (2) ◽  
pp. 611-615 ◽  
Author(s):  
Hyunah Choo ◽  
James R. Beadle ◽  
Earl R. Kern ◽  
Mark N. Prichard ◽  
Kathy A. Keith ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Oral Bioavailability ◽  
Dna Viruses ◽  
B Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Antiviral Activities ◽  
Acyclic Nucleoside

ABSTRACT Three acyclic nucleoside phosphonates are currently approved for clinical use against infections caused by cytomegalovirus (Vistide), hepatitis B virus (Hepsera), and human immunodeficiency virus type 1 (Viread). This important antiviral class inhibits viral polymerases after cellular uptake and conversion to their diphosphates, bypassing the first phosphorylation, which is required for conventional nucleoside antivirals. Small chemical alterations in the acyclic side chain lead to marked differences in antiviral activity and the spectrum of activity of acyclic nucleoside phosphonates against various classes of viral agents. We synthesized a new class of acyclic nucleoside phosphonates based on a 5-phosphono-pent-2-en-1-yl base motif in which the oxygen heteroatom usually present in acyclic nucleoside phosphonates has been replaced with a double bond. Since the intrinsic phosphonate moiety leads to low oral bioavailability and impaired cellular penetration, we also prepared the hexadecyloxypropyl esters of the 5-phosphono-pent-2-en-1-yl nucleosides. Our earlier work showed that this markedly increases antiviral activity and oral bioavailability. Although the 5-phosphono-pent-2-en-1-yl nucleosides themselves were not active, the hexadecyloxypropyl esters were active against DNA viruses and hepatitis B virus, in vitro. Notably, the hexadecyloxypropyl ester of 9-(5-phosphono-pent-2-en-1-yl)-adenine was active against hepatitis B virus mutants resistant to lamivudine, emtricitabine, and adefovir.

Sign in / Sign up

Export Citation Format

Share Document