Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitorof 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

doi:10.1002/cmdc.200700311

Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitorof 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

Dipartimento di Scienze del Farmaco

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
pagine (da-a)	771-779
Numero di pagine	9
Rivista	ChemMedChem
Volume	3
Numero di pubblicazione	5
DOI	https://doi.org/10.1002/cmdc.200700311
Stato di pubblicazione	Pubblicato - 19 mag 2008

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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.",

keywords = "Bioisostere, Chemotherapeutic agent, Click chemistry, FK866, NAD, Triazole",

author = "Ubaldina Galli and Emanuela Ercolano and Lorenzo Carraro and {Blasi Roman}, {Cintia R.} and Giovanni Sorba and Canonico, {Pier Luigi} and Genazzani, {Armando A.} and Tron, {Gian Cesare} and Billington, {Richard A.}",

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AU - Galli, Ubaldina

AU - Ercolano, Emanuela

AU - Carraro, Lorenzo

AU - Blasi Roman, Cintia R.

AU - Sorba, Giovanni

AU - Canonico, Pier Luigi

AU - Genazzani, Armando A.

AU - Tron, Gian Cesare

AU - Billington, Richard A.

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

Abstract

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