title: Brain delivery of HIV protease inhibitors.
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.
authors.affiliation: Medicinal Pharmaceutical Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt. Sheha@acc.aun.edu.eg
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Sheha
authors.forename: Nawal A
authors.initials: NA
authors.lastname: el-Koussi
authors.forename: Hassan H
authors.initials: HH
authors.lastname: Farag
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004355:Drug Stability; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis*; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D017320:HIV Protease Inhibitors; D007546:Isoquinolines