A novel class of highly potent multidrug resistance reversal agents: Disubstituted adamantyl derivatives

Novel disubstituted adamantyl derivatives were synthesized and evaluated in a P-glycoprotein dependent multidrug resistance cancer cell line. The hit to lead optimization provided potent MDR reversal agents. Some potent adamantyl derivatives were more than 10-fold more potent than verapamil without considerable intrinsic cytotoxicity. The 3-trifluorophenyl derivative 14f did not affect the metabolism of CYP450 3A4, whereas most of MDR revertants had a weak inhibitory effect.

Graphical abstractThe synthesis and SAR of a new class of potent MDR reversal agents are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide