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Discovery of pyridine-2-ones as novel class of multidrug resistance (MDR) modulators: first structure-activity
Sören Krawczyk1, Monika Otto, Alexander Otto
1Institute of Pharmacy, Martin Luther University, 06120 Halle, Germany.
Abstract:
A novel facile synthesis led to pyridine-2-one target structures of which first series with varying substituents have been yielded and biologically characterized as novel multidrug resistance (MDR) modulators inhibiting P-glycoprotein (P-gp). Structure-activity relationships prove a dependency of the MDR-modulating properties from the kind and positioning of hydrogen bond acceptor functions within the molecular skeleton. Cyano functions turned out as biologically effective substituents for a potential hydrogen bonding to the protein target structure.
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