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

Article abstract of DOI:10.1021/jm00014a031

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 as the substitution pattern at the nitrogen atom is crucial for activity of the compounds.Incorporation of the ether oxygen into a benzofuran substructure, which renders the compound an arylethanolamine, decreased biologic activity.Highest activity could be observed with the arylpiparazines 4f-h, which not only completely restored daunomycin sensitivity but also showed moderate activity in restoring etoposide toxicity.