Nucleotide analogues require only two phosphorylation steps whereas nucleoside analogues require three steps. Reduction in the phosphorylation requirement may allow more rapid and complete conversion of drugs to their active metabolites. Such considerations have led to the development of phosphonate nucleotide analogues such as tenofovir. Tenofovir disoproxil fumarate (Tenofovir DF) is the prodrug of  tenofovir. Tenofovir is an acyclic adenosine derivative. The acyclic nature of the compound and its phosphonate moiety are unique structural features among the approved NRTIs. Tenofovir DF is hydrolyzed enzymatically to tenofovir which exhibits anti-HIV activity. It was developed by the synthesis and broad spectrum antiviral activity of 2,3-dihydroxypropyladenine. Tenofovir DF was the first nucleotide reverse-transcriptase inhibitor approved by the FDA for the treatment of HIV-1 infection in October 2001.
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