Pronucleotides: toward the in vivo delivery of antiviral and anticancer nucleotides.
To overcome the many hurdles preventing the use of antiviral and anticancer nucleosides as therapeutics, the development of a prodrug methodology (i.e., pronucleotide) for the in vivo delivery of nucleotides has been proposed as a solution. The ideal pronucleotide should be non-toxic, stable in plasma and blood, capable of being i. v. and/or orally dosed, and intracellularly convertible to the corresponding nucleotide. Although this goal has yet to be achieved, many clever and imaginative pronucleotide approaches have been developed, which are likely to be important pharmacological tools. This review will discuss the major advances and future directions of the emerging field of antiviral and anticancer pronucleotide design and development.
Wagner
C R
CR
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Iyer
V V
VV
McIntee
E J
EJ
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015226:Dinucleoside Phosphates / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D004341:Drug Evaluation; D004355:Drug Stability; D006801:Humans; D007262:Infusions, Intravenous; D009711:Nucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010743:Phospholipids / Q000737:chemistry / Q000627:therapeutic use; D010756:Phosphoric Acids / Q000737:chemistry / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D000577:Amides; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015226:Dinucleoside Phosphates; D004337:Drug Carriers; D009711:Nucleotides; D010743:Phospholipids; D010756:Phosphoric Acids; D011355:Prodrugs; C011067:phosphoramidic acid; D010727:Phosphoric Diester Hydrolases