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

Ubaldina Galli; Emanuela Ercolano; Lorenzo Carraro; Roman CR Blasi; 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 inhibitor of NAD salvage.

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

University of Eastern Piedmont

Research output: Contribution to journal › Article › 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.

Original language	English
Pages (from-to)	771-779
Number of pages	0
Journal	ChemMedChem
Volume	3
Issue number	5
DOIs	https://doi.org/10.1002/cmdc.200700311
Publication status	Published - May 2008

Keywords

Acrylamides
Antineoplastic Agents
Catalysis
Cell Line
Tumor
Cell Survival
Copper
Humans
NAD
Piperidines
Triazoles

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cmdc.200700311

Cite this

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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.",

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

year = "2008",

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doi = "10.1002/cmdc.200700311",

language = "English",

volume = "3",

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journal = "ChemMedChem",

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T1 - Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage.

AU - Galli, Ubaldina

AU - Ercolano, Emanuela

AU - Carraro, Lorenzo

AU - Blasi, Roman CR

AU - Sorba, Giovanni

AU - Canonico, Pier Luigi

AU - Genazzani, Armando A.

AU - Tron, Gian Cesare

AU - Billington, Richard A.

PY - 2008/5

Y1 - 2008/5

N2 - 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.

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KW - Acrylamides

KW - Antineoplastic Agents

KW - Catalysis

KW - Cell Line

KW - Tumor

KW - Cell Survival

KW - Copper

KW - Humans

KW - NAD

KW - Piperidines

KW - Triazoles

U2 - 10.1002/cmdc.200700311

DO - 10.1002/cmdc.200700311

M3 - Article

SN - 1860-7179

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JO - ChemMedChem

JF - ChemMedChem

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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