[Hydrolysis kinetics of stobadine acyl-derivatives, the prodrug forms of free oxygen radical extinguishers. Part 3. Hydrolysis in a neutral medium].
The pyridoindole derivative stobadin, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3b]-indole] is a perspective antiarrhythmic, antihistamine, anaesthetic, antiulcerous drug capable of extinguishing free oxygen radical. Its prodrug forms--N(5)- acyl-substituted stobadine--of the active substance--stobadine--have been prepared and it is assumed that the will be hydrolyzed in the organism and the active substance will be released in higher concentrations in different biological tissues. The present paper is concerned with the investigation of the kinetics of the hydrolysis of 13 acyl derivatives of stobadine in the medium of a buffer solution of pH 7 at temperatures of 70 degrees C and 75 degrees C spectrophotometrically in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the drugs under study. The profile of log k--pH of substances was determined.
Ondrásová
M
M
Katedra farmaceutickej chémie Farmaceutickej fakulty Univerzity Komenského, Bratislava.
Stankovicová
M
M
Bezáková
Z
Z
Benes
L
L
D002243:Carbolines / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D011355:Prodrugs / Q000737:chemistry*
D002243:Carbolines; D016166:Free Radical Scavengers; D011355:Prodrugs; C100106:dicarbine