Evolution of an amino acid based prodrug approach: stay tuned.
Evolution of an amino acid based prodrug approach: stay tuned.
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DOI：
10.1021/mp300663j
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发表时间：
2013-02-04
影响因子：
4.9
通讯作者：
McKenna CE
中科院分区：
文献类型：
--
作者：
Krylov IS;Kashemirov BA;Hilfinger JM;McKenna CE
Certain acyclic nucleoside phosphonates (ANPs) such as (S)-HPMPC (cidofovir, Vistide®) and (S)-HPMPA have been shown to be active against a broad spectrum of DNA and retroviruses. However, their poor absorption as well as their toxicity limit the utilization of these therapeutics in the clinic. Nucleoside phosphonates are poorly absorbed primarily due to the presence of the phosphonic acid group, which ionizes at physiological pH. When dosed intravenously they display dose-limiting nephrotoxicity due to their accumulation in the kidney. To overcome these limitations, nucleoside phosphonate prodrug strategies have taken center stage in the development pathway and a number of different approaches are at various stages of development. Our efforts have focused on the development of ANP prodrugs in which a benign amino acid promoiety masks a phosphonate P-OH via a hydroxyl side chain. The design of these prodrugs incorporates multiple chemical groups (the P−X−C linkage, the amino acid stereochemistry, the C-terminal and N-terminal functional groups) that can be been tuned to modify absorption, pharmacokinetic and efficacy properties with the goal of improving overall prodrug performance.
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影响因子：
4.9
作者：
Eriksson, Ulrika;Peterson, Larryn W.;McKenna, Charles E.
通讯作者：
McKenna, Charles E.
影响因子：
5.6
作者：
Chicca, Andrea;Raduner, Stefan;Gertsch, Juerg
通讯作者：
Gertsch, Juerg
影响因子：
3.7
作者：
Bretschneider, B;Brandsch, M;Neubert, R
通讯作者：
Neubert, R
影响因子：
2.7
作者：
Eriksson, Ulrika;Hilfinger, John M.;McKenna, Charles E.
通讯作者：
McKenna, Charles E.
DOI：
10.1006/bbrc.1998.8628
发表时间：
1998-05-19
影响因子：
3.1
作者：
Ganapathy, ME;Huang, W;Leibach, FH
通讯作者：
Leibach, FH