Larryn W Peterson1, Charles E McKenna. 1. University of Southern California, Department of Chemistry, Los Angeles, CA 90089-0744, USA. mckenna@usc.edu
Abstract
Nucleotide analogues have been well accepted as therapeutic agents active against a number of viruses. However, their use as antiviral agents is limited by the need for phosphorylation by endogenous enzymes, and if the analogue is orally administered, by low bioavailability due to the presence of an ionizable diacid group. To circumvent these limitations, a number of prodrug approaches have been proposed. The ideal prodrug achieves delivery of a parent drug by attachment of a non-toxic moiety that is stable during transport and delivery, but is readily cleaved to release the parent drug once at the target. Here, a brief overview of several promising prodrug strategies currently under development is given.
Nucleotide anpan>alogues have been well accepted as therapeutic agents active against a number of viruses. However, their use as anpan>tiviral agents is limited by the need for phosphorylation by endogenous enzymes, anpan>d if the anpan>alogue is orally administered, by low bioavailability due to the presence of anpan> pan> class="Disease">ionizable diacid group. To circumvent these limitations, a number of prodrug approaches have been proposed. The ideal prodrug achieves delivery of a parent drug by attachment of a non-toxic moiety that is stable during transport and delivery, but is readily cleaved to release the parent drug once at the target. Here, a brief overview of several promising prodrug strategies currently under development is given.
Authors: C McGuigan; H W Tsang; D Cahard; K Turner; S Velazquez; A Salgado; L Bidois; L Naesens; E De Clercq; J Balzarini Journal: Antiviral Res Date: 1997-08 Impact factor: 5.970
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Authors: Larryn W Peterson; Monica Sala-Rabanal; Ivan S Krylov; Michaela Serpi; Boris A Kashemirov; Charles E McKenna Journal: Mol Pharm Date: 2010-10-07 Impact factor: 4.939
Authors: Valeria M Zakharova; Michaela Serpi; Ivan S Krylov; Larryn W Peterson; Julie M Breitenbach; Katherine Z Borysko; John C Drach; Mindy Collins; John M Hilfinger; Boris A Kashemirov; Charles E McKenna Journal: J Med Chem Date: 2011-08-03 Impact factor: 7.446
Authors: Valeria M Zakharova; Ivan S Krylov; Michaela Serpi; Boris A Kashemirov; Charles E McKenna Journal: Phosphorus Sulfur Silicon Relat Elem Date: 2011
Authors: Larryn W Peterson; Jae-Seung Kim; Paul Kijek; Stefanie Mitchell; John Hilfinger; Julie Breitenbach; Kathy Borysko; John C Drach; Boris A Kashemirov; Charles E McKenna Journal: Bioorg Med Chem Lett Date: 2011-05-03 Impact factor: 2.823
Authors: Ivan S Krylov; Valeria M Zakharova; Michaela Serpi; Ralf Haiges; Boris A Kashemirov; Charles E McKenna Journal: J Org Chem Date: 2011-11-30 Impact factor: 4.354