SYNTHESIS, PHARMACOLOGICAL ACTIVITY, AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF A SERIES OF PROPAFENONE-RELATED MODULATORS OF MULTIDRUG-RESISTANCE

A series of [(o-acylaryl)oxy]propanolamines have been prepared and eva luated for multidrug resistance-reverting activity in a human tumor ce ll model. Structure-activity relationship studies indicate that the ph enylpropiophenone moiety as well as the substitution pattern at the ni trogen atom is crucial for activity of the compounds. Incorporation of the ether oxygen into a benzofuran substructure, which renders the co mpound an arylethanolamine, decreased biologic activity. Highest activ ity could be observed with the arylpiparazines 4f-h, which not only co mpletely restored daunomycin sensitivity but also showed moderate acti vity in restoring etoposide toxicity.