Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides

Article abstract of DOI:10.1021/jm00013a017

A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the CH^RC/5 cell line.Among them the acridone derivatives were the most potent.A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain.Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone.On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy-9-oxo-N-<4-<2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol- 2-yl)ethyl>phenyl>-4-acridinecarboxamide (84) has been selected for further development.