TY - JOUR
T1 - Redox derivatives of tranylcypromine
T2 - Syntheses, properties, and monoamine oxidase inhibitor activity of some chemical delivery systems
AU - Prókai‐Tátrai, Katalin
AU - Pop, Emil
AU - Anderson, Wesley
AU - Lin, Jun‐Liang ‐L
AU - Brewster, Marcus E.
AU - Bodor, Nicholas
PY - 1991/3
Y1 - 1991/3
N2 - Several brain‐targeting chemical delivery systems (CDS) based on a dihydropyridine ↔ pyridinium salt type redox system were synthesized for the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). The dihydronicotinate moiety was chemically attached to the amino group of TCP by either an amide or substituted carbamate linkages. Physicochemical studies of the new derivatives, including chromatographic Rm determinations, were performed. Only the substituted carbamate‐type derivatives manifested an increased lipophilicity relative to the parent compound. In vitro oxidation stability studies were also performed on selected derivatives using a ferricyanide‐mediated method. Results of this assay showed that the dihydropyridine‐type derivatives oxidized to the respective quaternary salt forms with stabilities which empirically correlated with other effective CDSs. Preliminary in vivo studies performed in rats indicated that some of the new derivatives exerted significant biological activity.
AB - Several brain‐targeting chemical delivery systems (CDS) based on a dihydropyridine ↔ pyridinium salt type redox system were synthesized for the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). The dihydronicotinate moiety was chemically attached to the amino group of TCP by either an amide or substituted carbamate linkages. Physicochemical studies of the new derivatives, including chromatographic Rm determinations, were performed. Only the substituted carbamate‐type derivatives manifested an increased lipophilicity relative to the parent compound. In vitro oxidation stability studies were also performed on selected derivatives using a ferricyanide‐mediated method. Results of this assay showed that the dihydropyridine‐type derivatives oxidized to the respective quaternary salt forms with stabilities which empirically correlated with other effective CDSs. Preliminary in vivo studies performed in rats indicated that some of the new derivatives exerted significant biological activity.
UR - http://www.scopus.com/inward/record.url?scp=0026029548&partnerID=8YFLogxK
U2 - 10.1002/jps.2600800313
DO - 10.1002/jps.2600800313
M3 - Article
C2 - 2051343
AN - SCOPUS:0026029548
VL - 80
SP - 255
EP - 261
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 3
ER -