Abstract
AbstractPhysicochemical properties of pharmacological interest were determined for ten 6H-pyrimido[2,1-a]isoindoles. The compounds studied were found to be weak bases with a pKa ranging from 2.38 to 3.46. Furthermore, the association constants of the studied compounds with cyclodextrins were examined. The formation of complexes was observed with 1:1 stoichiometry, γ-cyclodextrin was found to be the best complexing. Finally, the electrochemical oxidation of 6H-pyrimido[2,1-a]-isoindoles in 0.1 mol dm−3 sodium perchlorate in acetonitrile was studied as a model of their possible metabolic degradation. It was found to be a one-electron process, and the values of the half-wave potentials are in the range of 1.34–1.62 V (vs. Ag/AgNO3/NaClO4). The electrooxidation products of three selected compounds were prepared by preparative electrolysis and subsequently identified by mass spectrometry. From the data obtained, it is evident that the electrochemical oxidation of the 6H-pyrimido[2,1-a]isoindoles begins with the formation of N-oxides, followed by dimerization of the molecule or, contrary to this, by oxidative cleavage of the pyrimidine ring. From a metabolic point of view, N-oxidation is the corresponding process to this pathway.
Graphical abstract
Funder
Univerzita Karlova v Praze
Charles University
Publisher
Springer Science and Business Media LLC
Reference40 articles.
1. Heravi MM, Zadsirjan V (2020) RSC Adv 10:44247
2. Bortnick NM, Fegley MF (1961) Condensed heterocyclic nitriles. Chem Abstr 56:18335
3. Ghose K, Rama Rao VA, Bailey J, Coppen A (1978) Psychopharmacology 57:109
4. Cliffe IA, Lien EL, Mansell HL, Steiner KE, Todd RS, White AC, Black RM (1992) J Med Chem 35:1169
5. Pokholenko AA, Voitenko ZV, Kovtunenko VA (2004) Russ Chem Rev 73:771