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Synthesis and Early Development of Hexadecyloxypropyl-cidofovir: An Oral Antipoxvirus Nucleoside Phosphonate
Department of Medicine, Division of Infectious Disease, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA
Veterans Medical Research Foundation, San Diego, CA 92161, USA
Received: 26 August 2010; in revised form: 8 September 2010 / Accepted: 8 September 2010 / Published: 30 September 2010
Abstract: Hexadecyloxypropyl-cidofovir (HDP-CDV) is a novel ether lipid conjugate of (S)-1-(3-hydroxy-2-phosphonoylmethoxypropyl)-cytosine (CDV) which exhibits a remarkable increase in antiviral activity against orthopoxviruses compared with CDV. In contrast to CDV, HDP-CDV is orally active and lacks the nephrotoxicity of CDV itself. Increased oral bioavailability and increased cellular uptake is facilitated by the lipid portion of the molecule which is responsible for the improved activity profile. The lipid portion of HDP-CDV is cleaved in the cell, releasing CDV which is converted to CDV diphosphate, the active metabolite. HDP-CDV is a highly effective agent against a variety of orthopoxvirus infections in animal models of disease including vaccinia, cowpox, rabbitpox and ectromelia. Its activity was recently demonstrated in a case of human disseminated vaccinia infection after it was added to a multiple drug regimen. In addition to the activity against orthopoxviruses, HDP-CDV (CMX001) is active against all double stranded DNA viruses including CMV, HSV-1, HSV-2, EBV, adenovirus, BK virus, orf, JC, and papilloma viruses, and is under clinical evaluation as a treatment for human infections with these agents.
Keywords: antiviral drugs; Cidofovir; HPMPA; acyclic nucleoside phosphonates; smallpox; vaccinia; biodefense
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MDPI and ACS Style
Hostetler, K.Y. Synthesis and Early Development of Hexadecyloxypropyl-cidofovir: An Oral Antipoxvirus Nucleoside Phosphonate. Viruses 2010, 2, 2213-2225.
Hostetler KY. Synthesis and Early Development of Hexadecyloxypropyl-cidofovir: An Oral Antipoxvirus Nucleoside Phosphonate. Viruses. 2010; 2(10):2213-2225.
Hostetler, Karl Y. 2010. "Synthesis and Early Development of Hexadecyloxypropyl-cidofovir: An Oral Antipoxvirus Nucleoside Phosphonate." Viruses 2, no. 10: 2213-2225.