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The Effect of Dihydronicotinate N-Substitution on the Brain-Targeting Efficacy of a Zidovudine Chemical Delivery System

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Abstract

Enhanced brain delivery of zidovudine (AZT) has been demonstrated using a redox-based chemical delivery system (CDS). Optimization of the prototype AZT-CDS (5′-[(1-methyl-1,4-dihydropyridin-3-yl)carbonyl]-3′-azido-3′-deoxythymidine) was investigated by manipulation of the N-methyl group present on the dihydronicotinate portion of the molecule and examining the release of AZT in vivo in a rat model. Of the five compounds examined, all produced higher brain levels and lower blood levels of AZT than did AZT itself. In comparing the novel AZT-CDS analogues to the N-methyl benchmark, the N-propyl system proved to be the most efficient of the compounds tested.

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Brewster, M.E., Pop, E., Braunstein, A.J. et al. The Effect of Dihydronicotinate N-Substitution on the Brain-Targeting Efficacy of a Zidovudine Chemical Delivery System. Pharm Res 10, 1356–1362 (1993). https://doi.org/10.1023/A:1018986217181

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