Reversal of multidrug resistance by bis(phenylalkyl)amines and structurally related compounds.

We have previously reported that multidrug (MDR)-reversal activity can be exerted by compounds in which two ring structures of certain types are connected by one alkyl bridge to a secondary or tertiary amine group. In the present investigation we studied the MDR-reversal activity of compounds in which the two ring structures were connected by separate alkyl bridges to the amine group. The structure-activity relationship of these compounds verified previous findings on the structural features that support MDR-reversal activity as well as the features that reduce such activity. In addition, the present study reveals additional chemical groups and ring structures that support MDR-reversal activity as well as those that reduce it.