- Pradefovir: A prodrug that targets adefovir to the liver for the treatment of hepatitis B
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Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the r
- Reddy, K. Raja,Matelich, Michael C.,Ugarkar, Bheemarao G.,Gómez-Galeno, Jorge E.,DaRe, Jay,Ollis, Kristin,Sun, Zhili,Craigo, William,Colby, Timothy J.,Fujitaki, James M.,Boyer, Serge H.,Van Poelje, Paul D.,Erion, Mark D.
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p. 666 - 676
(2008/09/19)
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- LEWIS ACID MEDIATED SYNTHESIS OF CYCLIC ESTERS
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Methods for the synthesis of cyclic phosphonic acid diesters from 1,3-diols are described, whereby cyclic phosphonic acid diesters are produced by reacting a chiral 1,3-diol and an activated phosphonic acid in the presence of a Lewis acid.
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Page/Page column 30
(2008/06/13)
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- Design, Synthesis, and Characterization of a Series of Cytochrome P 450 3A-Activated Prodrugs (HepDirect Prodrugs) Useful for Targeting Phosph(on)ate-Based Drugs to the Liver
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A new class of phosphate and phosphonate prodrugs, called HepDirect prodrugs, is described that combines properties of rapid liver cleavage with high plasma and tissue stability to achieve increased drug levels in the liver. The prodrugs are substituted c
- Erion, Mark D.,Reddy, K. Raja,Boyer, Serge H.,Matelich, Michael C.,Gomez-Galeno, Jorge,Lemus, Robert H.,Ugarkar, Bheemarao G.,Colby, Timothy J.,Schanzer, Juergen,Van Poelje, Paul D.
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p. 5154 - 5163
(2007/10/03)
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- Process for preparation of cyclic prodrugs of PMEA and PMPA
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The method of preparing compounds of Formula I is described: wherein: M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmethoxyethyl)adenine, and (R)-9-(2-phosphonylmethoxypropyl)adenine; wherein V is phenyl, optionally substituted with 1-2 substituents selected from a group consisting of fluoro, chloro, and bromo; comprising: coupling a chiral 1-phenylpropane-1,3-diol, wherein the phenyl may be optionally substituted, with MPOCl2 or an N-6 substituted analogue thereof. Additionally, methods and salt forms are described that enable isolation and purification of the desired isomer.
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- Novel phosphonic acid based prodrugs of PMEA and its analogues
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Prodrugs of Formula I, their uses, their intermediates, and their method of manufacture are described: 1wherein: M and V are cis to one another and MPO3H2 is a phosphonic acid selected from the group consisting of 9-(2-phosphonylmet
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