Discovery of pyridine-2-ones as novel class of multidrug resistance (MDR) modulators: First structure–activity relationships

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• 作者：Sö ; ren  ; Krawczyk^a ; Monika  ; Otto^a ; Alexander  ; Otto^a ; Claudius  ; Coburger^a ; Martin  ; Krug^a ; Marianne  ; Seifert^a ; Volkmar  ; Tell^a ; José ; f  ; Molná ; r^b ; Andreas  ; Hilgeroth^a ;   ; ^{andreas.hilgeroth@pharmazie.uni-halle.de}
• 关键词：Structure&ndash ; activity relationships (SAR) ; Multidrug resistance (MDR) ; P-glycoprotein (P-gp) ; Lead structure ; Efflux pump inhibition
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2011
• 出版时间：1 November 2011
• 年：2011
• 卷：19
• 期：21
• 页码：6309-6315
• 全文大小：243 K

文摘

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.