1-[4-(2-Aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines: A novel series of highly potent revertants of P-glycoprotein associated multidrug resistance

The 1-[4-(2-aminoethoxy)phenylcarbonyl]-3,5-bis-(benzylidene)-4-oxopiperidines 5–8 are a novel cluster of highly potent P-glycoprotein dependent multidrug resistance (MDR) revertants. Using a concentration of 4 μg/mL, these compounds possess 11–43 times the potency of verapamil in reversing MDR in murine L-5178 lymphoma cells transfected with the human MDR1 gene. Structure–activity relationships reveal that the attachment of the N-aroyl group to various 3,5-bis(benzylidene)-4-piperidones is essential for MDR reversal to occur. In terms of potencies, the 1-piperidinyl group is the preferred terminal amine while the 4-methyl and 4-chloro substituents are the optimal groups for placement in the benzylidene aryl rings.

Optimal activity is shown when R is a methyl or chloro group and X is a 1-piperidyl substituent.Figure optionsDownload as PowerPoint slide