1, 2-dihydroisoquinoline-N-acetic acid derivatives as new carriers for specific brain delivery I: synthesis and estimation of oxidation kinetics using multivariate calibration method.
In order to overcome the slow oxidation of 1, 2-dihydro-N-alkylisoquinoline, 1, 2-dihydroisoquinoline-N-acetic acid derivatives (3b-d) were designed and synthesized as new chemical delivery systems (CDS) for the brain. Molecular orbital calculations for the suggested derivatives revealed that these carriers are stable against oxidation. However, hydrolysis to their corresponding anions will accelerate the rate of oxidation, and accordingly increase the efficiency of brain specific delivery. A multivariate calibration method for in vitro determination of the oxidation rate for the suggested brain specific chemical delivery system is described. The method is based on measurement of individual rates of oxidation of prepared 1, 2-dihydroisoquinolines, using silver ions to provide the corresponding quaternary forms. Components of binary mixtures formed through the oxidation step (composed of the dihydro-compound and its quaternary form), showed a considerable degree of spectral overlapping - more than 90% in all cases. Resolution of these binary mixtures under investigation has been accomplished mainly using classical least squares analysis. Kinetic oxidation data of the tested compounds revealed that these new CDSs have a reasonable oxidation rate for efficient brain delivery.
Mahmoud
Sahar
S
Dept.Pharm.Med.Chem., Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Aboul-Fadl
Tarek
T
Sheha
Mahmoud
M
Farag
Hassan
H
Mouhamed
Abdel-Maaboud I
AM
D019342:Acetic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D001921:Brain; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D015999:Multivariate Analysis; D010084:Oxidation-Reduction; D011789:Quantum Theory; D012835:Silver Nitrate / Q000737:chemistry; D013329:Structure-Activity Relationship
C477540:1, 2-dihydroisoquinoline-N-acetic acid; C482263:1,2-dihydro-N-carboxymethylisoquinoline; D004337:Drug Carriers; D007546:Isoquinolines; D012835:Silver Nitrate; D019342:Acetic Acid