Synthesis and Biological Evaluation of Isosteric Analogues of FK866, an Inhibitor of NAD Salvage

✍ Scribed by Ubaldina Galli; Emanuela Ercolano; Lorenzo Carraro; Cintia R. Blasi Roman; Giovanni Sorba; Pier Luigi Canonico; Armando A. Genazzani; Gian Cesare Tron; Richard A. Billington

• Book ID: 102101575
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 275 KB
• Volume: 3
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200700311

✦ Synopsis

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.