Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Sep;5(5):431-41.
doi: 10.1016/j.apsb.2015.07.002. Epub 2015 Sep 2.

Adenine: an important drug scaffold for the design of antiviral agents

Changyuan Wang  1 , Zhendong Song  1 , Haiqing Yu  1 , Kexin Liu  1 , Xiaodong Ma  1
Affiliations
Review

Adenine: an important drug scaffold for the design of antiviral agents

Changyuan Wang et al. Acta Pharm Sin B. 2015 Sep.

Abstract

Adenine derivatives, in particular the scaffold bearing the acyclic nucleoside phosphonates (ANPS), possess significant antiviral and cytostatic activity. Till now, several effective adenine derivatives have been marketed for the treatment of HIV, HBV, CMV and other virus-infected diseases. These compounds are represented by tenofovir (PMPA), a medicine for both HIV and HBV, and adefovir as an anti-HBV agent. More than this, other analogs, such as GS9148, GS9131, and GS7340, are also well-known anti-viral agents that have been progressed to the clinical studies for their excellent activity. In general, the structures of these compounds include an adenine nucleobase linked to a phosphonate side chain. Considerable structural modifications on the scaffold itself and the peripheral sections were made. The structure-activity relationships (SARs) of this skeleton will provide valuable clues to identify more effective adenine derivatives as antiviral drugs. Here, we systematically summarized the SARs of the adenine derivatives, and gave important information for further optimizing this template.

Keywords: Acyclic nucleoside phosphonates; Adenine; Antiviral; Scaffold; Structure–activity relationship.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1
Figure 1
Structures of the novel adenine derivatives as antiviral agents.
Figure 2
Figure 2
Adenine derivatives with substituents (Cl, MeS) at the C-2 position.
Figure 3
Figure 3
Adenine derivatives with substituents (NH2, F) at the C-2 position.
Figure 4
Figure 4
Adenine derivatives with substituents (NH2, F) at the C-6 position.
Figure 5
Figure 5
Adenine derivatives with substituents at the C-6 position.
Figure 6
Figure 6
Structures of the 9-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine (HPMPDAP) and its cyclic form as potential drug candidates against poxvirus infections.
Figure 7
Figure 7
Structures of carbocyclic phosphonate analogs of dideoxy-adenine nucleotides.
Figure 8
Figure 8
Structures of adenosine 5′-phosphonate analogs.
Figure 9
Figure 9
Structures of GS9148 analogs.
Figure 10
Figure 10
Structures of 2′-fluorine-modified nucleoside phosphonates 52 and 53.
Figure 11
Figure 11
Structures of phosphoramidate ProTides 54a–c.
Figure 12
Figure 12
Structures of novel adenine derivative FMCA and FMCAP.
Figure 13
Figure 13
Structures of 5′-norcarbocyclic adenosine phosphonic acid 57 and its bis-SATE prodrug 58.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Holý A. Phosphonomethoxyalkyl analogs of nucleotides. Curr Pharm Des. 2003;9:2567–2592. - PubMed
    1. de Clercq E, Holý A. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat Rev Drug Discov. 2005;4:928–940. - PubMed
    1. de Clercq E. Antiviral drug discovery: ten more compounds, and ten more stories (part B) Med Res Rev. 2009;29:571–610. - PubMed
    1. de Clercq E. In search of a selective therapy of viral infections. Antivir Res. 2010;85:19–24. - PubMed
    1. Naesens L, Snoeck R, Andrei G, Balzarini J, Neyts J, de Clercq E. HPMPC (cidofovir), PMEA (adefovir) and related acyclic nucleoside phosphonate analogs: a review of their pharmacology and clinical potential in the treatment of viral infections. Antivir Chem Chemother. 1997;8:1–23.