Medicinal chemistry of nucleoside phosphonate prodrugs for antiviral therapy

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Pertusati, Fabrizio ; Serpi, Michaela ; McGuigan, Christopher (2011)

Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However, phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug structures of biologically active phosphonate analogues have been developed. The rationale behind the design of such agents is to achieve temporary blockade of the free phosphonic functional group until their systemic absorption and delivery, allowing the release of the active drug only once at the target. In this paper, an overview of acyclic and cyclic nucleoside phosphonate prodrugs, designed as antiviral agents, is presented.
  • References (10)

    1. De Clercq E & Neyts J. Antiviral agents acting as DNA or RNA chain terminators. Handb. Exp. Pharmacol. 2009:53-84.

    2. De Clercq E. The clinical potential of the acyclic (and cyclic) nucleoside phosphonates. The magic of the phosphonate bond. Biochemical Pharmacology 2011; 82:99-109.

    3. De Clercq E & Holý A. Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nat Rev Drug Discov 2005; 4:928-940.

    4. Holý A. Phosphonomethoxyalkyl analogs of nucleotides. Curr. Pharm. Des. 2003 9:2567- 2592.

    5. De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J & Maudgal PC. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986; 323:464-467.

    6. De Clercq E, Andrei G, Balzarini J, Leyssen P, Naesens L, Neyts J, Pannecouque C, Snoeck R, Ying C, Hockova D & Holý A. Antiviral Potential of a New Generation of Acyclic Nucleoside Phosphonates, the 6-[2-(Phosphonomethoxy)Alkoxy]-2,4-Diaminopyrimidines. NNNA 2005; 24:331 - 341.

    7. De Clercq E, Sakuma T, Baba M, Pauwels R, Balzarini J, Rosenberg I & Holý A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res. 1987; 8:261-272.

    8. De Clercq E. The acyclic nucleoside phosphonates from inception to clinical use: Historical perspective. Antiviral Res. 2007; 75:1-13.

    9. De Clercq E & Neyts J. Therapeutic potential of nucleoside/nucleotide analogues against poxvirus infections. Rev. in Med. Virol. 2004; 14:289-300.

    10. Dal Pozzo F, Andrei G, Holy A, Van Den Oord J, Scagliarini A, De Clercq E & Snoeck R. Activities of Acyclic Nucleoside Phosphonates against Orf Virus in Human and Ovine Cell Monolayers and Organotypic Ovine Raft Cultures. Antimicrob. Agents Chemother. 2005; 49:4843-4852. 1315923.

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