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Design, Synthesis and Activity of Ascorbic Acid Prodrugs of Nipecotic, Kynurenic and Diclophenamic Acids, Liable to Increase Neurotropic Activity

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Department of Pharmaceutical Sciences, via Fossato di Mortara 19, 44100 Ferrara, Italy, Department of Biology, General Physiology Section, via Borsari 46, 44100 Ferrara, Italy, and Department of Experimental Clinical Medicine, Pharmacology Section, via Fossato di Mortara 19, 44100 Ferrara, Italy, and Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA
Cite this: J. Med. Chem. 2002, 45, 3, 559–562
Publication Date (Web):December 21, 2001
https://doi.org/10.1021/jm015556r
Copyright © 2002 American Chemical Society

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    To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug.

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     Department of Pharmaceutical Sciences , Universita degli Studi di Ferrara.

     Department of Biology, Universita degli Studi di Ferrara.

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     Department of Experimental Clinical Medicine, Universita degli Studi di Ferrara.

     Medical College of Georgia.

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