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

Abstract

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.

“All in the Mind”? Brain-Targeting Chemical Delivery System of 17β-Estradiol (Estredox) Produces Significant Uterotrophic Side Effect

“…Most prominently, inadequate chemical stability characteristics for this type of dihydropyridines are attributable to facile oxidation and an acid-catalyzed water addition [43]. The latter renders the CDSs unsuitable for the preferred oral administration in several therapeutic objectives, and also forecasts unacceptably short shelf-life [44]. Moreover, aqueous solubility is also of serious concern especially when even the parent drug is highly lipophilic (and, thus, poorly water-soluble), such as the case with E2 itself.…”

Further Insight into the Mechanism of the Novel Multicomponent Reactions Involving Isoquinoline and Dimethyl Acetylenedicarboxylate in the Presence of 3-Methylindole: Theoretical and Experimental Approach

“…Isoquinoline skeletons are seen within a large number of naturally occurring, biologically active, synthetic heterocyclic compounds , including such drugs as papaverine . Moreover, 1,2‐dihydroisoquinoline derivatives act as delivery systems that transport drugs through the otherwise highly impermeable blood–brain barrier and exhibit sedative , antidepressant , antitumor, and antimicrobial activities .…”

The anion exchange reaction of bis(isoquinoline) ionic liquids: self-assembly, crystal structures and thermal properties of ten novel d10 metal (Cu, Ag) halide/thiocyanate supramolecular polymers

“…In compound 3, DMF (dimethyl formamide) was located around the BIQHX 2+ and the inorganic anion cluster [Cu 4 I 8 ] 22 . The [Cu 4 I 8 ] 22 moiety lies about an inversion centre.…”

“…[15][16][17] To date, many heterocyclic nitrogen-containing organic cations have been widely used to construct supramolecular compounds with interesting structural and novel properties. [18][19][20][21] Among them, isoquinoline and its derivatives have received close attention because of their broad range of biological activities, [22][23][24][25][26] but less use in supramolecular assembly.…”