Brain Delivery of HIV Protease Inhibitors
- 25 March 2003
- journal article
- Published by Wiley in Archiv der Pharmazie
- Vol. 336 (1), 47-52
- https://doi.org/10.1002/ardp.200390003
Abstract
To overcome the problems of peptidomimetic drug delivery to the specific organs, the use of dihydropyridine ↔ pyridinium chemical delivery systems to deliver peptides to the brain is considered in this work. An HIV protease inhibitor lead compound; KNI 279 was selected for the study. The N‐alkylated dihydroisoquinoline derivatives of KNI‐279 were synthesized and tested for their ability to be oxidized by brain homogenate and showed good results with reasonable half‐life times specially for the N‐alkoxycarbonyl‐methyl derivative 8. The in‐vivo distribution of compound 8 proved the brain delivery and locked in property of HIV PR inhibitors in the brain. All the prepared compounds (both quaternary and dihydro derivatives) showed between 51 and 86 % HIV PR inhibitory activity compared to the parent compound.Keywords
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