Synthesis, antioxidant and anti-inflammatory activity of novel substituted ethylenediamines and ethanolamines. A preliminary quantitative structure-activity relationship study.

Six substituted oxo- or hydroxy-aminoethanols and ethylenediamines were synthesized and tested as anti-inflammatory agents. 1-Substituted 4-(2-aminoethylamino)-1-butanones and 1-substituted 4-(2-hydroxy-ethylamino)-1-butanones were prepared by reacting the appropriate 4-chloro-1-butanone with the corresponding aminoalcohol or ethylenediamine. 1-Substituted 4-(2-aminoethylamino)-1-butanols were prepared by the reduction of the ketones with NaBH4 or NaBH3CN. The RM values of the synthesized compounds were determined as an expression of their lipophilicity. The effect of these compounds on in vitro non-enzymatic lipid peroxidation, their hydroxyl radical scavenging activity and their ability to interact with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH) were studied. The effect of the synthesized compounds on inflammation, using the carrageenan induced rat paw edema model was studied. Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesized compounds. It was also attempted to correlate the above mentioned activities with some physicochemical parameters using a quantitative structure-activity relationship approach. The primary amino group appeared to be of importance for antioxidant activity in this series of compounds.