Synthesis, Pharmacologic Activity, and Structure-Activity Relationships of a Series of Propafenone-Related Modulators of Multidrug Resistance

摘要: A series of [(o-acylaryl)oxy]propanolamines have been prepared and evaluated for multidrug resistance-reverting activity in a human tumor cell model. Structure-activity relationship studies indicate that the phenylpropiophenone moiety as well substitution pattern at nitrogen atom is crucial compounds. Incorporation ether oxygen into benzofuran substructure, which renders compound an arylethanolamine, decreased biologic activity. Highest could be observed with arylpiparazines 4f-h, not only completely restored daunomycin sensitivity but also showed moderate restoring etoposide toxicity.