title: Discovery of pyridine-2-ones as novel class of multidrug resistance (MDR) modulators: first structure-activity relationships.
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.
authors.affiliation: Institute of Pharmacy, Martin Luther University, 06120 Halle, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Krawczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Otto
authors.forename: Alexander
authors.initials: A
authors.lastname: Otto
authors.forename: Claudius
authors.initials: C
authors.lastname: Coburger
authors.forename: Martin
authors.initials: M
authors.lastname: Krug
authors.forename: Marianne
authors.initials: M
authors.lastname: Seifert
authors.forename: Volkmar
authors.initials: V
authors.lastname: Tell
authors.forename: Joséf
authors.initials: J
authors.lastname: Molnár
authors.forename: Andreas
authors.initials: A
authors.lastname: Hilgeroth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011728:Pyridones