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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

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

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10.1002/cmdc.200700311

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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",

month = may,

doi = "10.1002/cmdc.200700311",

language = "English",

volume = "3",

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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.

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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

UN SDGs

Keywords

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