Brain-specific chemical delivery systems for beta-lactam antibiotics. Synthesis and properties of some dihydropyridine and dihydroiosquinoline derivatives of benzylpenicillin.

摘要: Six chemical delivery systems (CDS) were synthesized for benzylpenicillin in order to improve its transport across the blood-brain barrier. The CDS's based on a dihydropyridine----quaternary pyridinium ion redox system, analogous naturally occurring NADH----NAD+ system. Two different types of prepared: esters diols which other hydroxyl group is esterified by dihydrotrigonelline and amino alcohols amine acylated dihydrotrigonelline, or 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid. Lipophilicities proved be much higher than those using Rm values as lipophilicity indexes. Upon oxidation, all gave quaternary forms. Kinetic studies buffer (pH profiles) indicated that salts released pH range 5-9 via hydrolysis. acidic media yielded major reaction product 6-hydroxy-1,4,5,6-tetrahydropyridines result water addition, while basic conditions was released. addition dependent structure, being more prevalent case "amide-esters". dihydroisoquinoline CDS rather stable 5-8.