title: Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage.
abstract: One of the great challenges of medicinal chemistry is to create novel, effective, chemotherapeutic agents that show specificity for cancer cells combined with low systemic toxicity. A novel idea is to target the enzymes of the NAD biosynthesis and recycling pathways given that cancer cells display a higher NAD turnover rate than healthy cells. To this end, the compound FK866 (APO866; (E)-N-[4-(1-benzoylpiperidin-4-yl) butyl]-3-(pyridin-3-yl) acrylamide), which blocks nicotinamide phosphoribosyltransferase (NMPRTase) has entered clinical trials as a potential chemotherapeutic agent. Here we report the synthesis of analogues of FK866 synthesized by click chemistry.
authors.affiliation: Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center Università degli Studi del Piemonte Orientale A. Avogadro, Via Bovio 6, 28100 Novara, Italy.
authors.forename: Ubaldina
authors.initials: U
authors.lastname: Galli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ercolano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Carraro
authors.forename: Cintia R
authors.initials: CR
authors.lastname: Blasi Roman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorba
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Tron
authors.forename: Richard A
authors.initials: RA
authors.lastname: Billington
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D006801:Humans; D009243:NAD / Q000378:metabolism*; D010880:Piperidines / Q000138:chemical synthesis*; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; C480543:N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide; D010880:Piperidines; D014230:Triazoles; D009243:NAD; D003300:Copper