Designing a pronucleotide stratagem: lessons from amino acid phosphoramidates of anticancer and antiviral pyrimidines.
Phosphoramidate pronucleotides have proven to be an effective strategy for the intracellular delivery of nucleoside 5'-monophosphates. This review will summarize our efforts to understand the in vitro and in vivo behavior of phosphoramidate monoesters of 3'-azido-3'-deoxythymidine (AZT), 3'-fluoro-3'-deoxythymidine (FLT) and 5-fluoro-2'-deoxyuridine (FUdR). Insights drawn from these studies have proved valuable for the future design of phosphoramidate-based pronucleotides.
Drontle
Dan P
DP
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Wagner
Carston R
CR
D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005468:Fluorodeoxyuridylate / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010756:Phosphoric Acids / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D015215:Zidovudine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D000577:Amides; D000596:Amino Acids; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D009711:Nucleotides; D010756:Phosphoric Acids; D011355:Prodrugs; D011743:Pyrimidines; D005468:Fluorodeoxyuridylate; D015215:Zidovudine; C002854:alovudine