Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties

Novel series of N-benzyl 1,4-dihydropyridines have been prepared by facile syntheses. All relevant substituents of the molecular scaffold have been varied. The resulting compounds were biologically evaluated as P-glycoprotein (P-gp) inhibitors. Substitutions of the N-benzyl residue favour biological activity beside respective 3-ester functions. Most active compounds were further evaluated as multidrug resistance (MDR) modulators to restore the cytotoxic properties of varying daunorubicin applications.

Figure optionsDownload as PowerPoint slide