Galli Ubaldina, Ercolano Emanuela, Carraro Lorenzo, Blasi Roman Cintia R, Sorba Giovanni, Canonico Pier Luigi, Genazzani Armando A, Tron Gian Cesare, Billington Richard A
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.
ChemMedChem. 2008 May;3(5):771-9. doi: 10.1002/cmdc.200700311.
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.
药物化学面临的重大挑战之一是研发出新型、有效且具有化学治疗作用的药物，这些药物要对癌细胞具有特异性，同时全身毒性较低。鉴于癌细胞的烟酰胺腺嘌呤二核苷酸（NAD）周转速率高于健康细胞，一个新的思路是靶向NAD生物合成和循环途径的酶。为此，阻断烟酰胺磷酸核糖基转移酶（NMPRTase）的化合物FK866（APO866；(E)-N-[4-(1-苯甲酰基哌啶-4-基)丁基]-3-(吡啶-3-基)丙烯酰胺）已作为一种潜在的化学治疗药物进入临床试验阶段。在此，我们报告通过点击化学合成的FK866类似物。
