Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage.

Ubaldina Galli, Emanuela Ercolano, Lorenzo Carraro, Cintia R Blasi Roman, Giovanni Sorba, Pier Luigi Canonico, Armando A Genazzani, Gian Cesare Tron, Richard A Billington

文献索引：ChemMedChem 3 , 771-779, (2008)

全文：HTML全文

摘要

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.