SYNTHESIS AND ACTIVITY AGAINST MULTIDRUG-RESISTANCE IN CHINESE-HAMSTER OVARY CELLS OF NEW ACRIDONE-4-CARBOXAMIDES

A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C -R/5 cell line. Among them the acridone derivatives were the most pote nt, A key feature is the presence of a dimethoxybenzyl or phenethylami ne cationic site, separated from the tricyclic lipophilic part by a ca rbamoylphenyl chain. Optimization led to compounds 2 orders of magnitu de more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-metho xy- isoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been s elected for further development.