Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)

An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displ...

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Autores principales: Safrygin, Alexander, Zhmurov, Petr, Dar’in, Dmitry, Silonov, Sergey, Kasatkina, Mariia, Zonis, Yulia, Gureev, Maxim, Krasavin, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409965/
https://www.ncbi.nlm.nih.gov/pubmed/34461785
http://dx.doi.org/10.1080/14756366.2021.1969386
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author Safrygin, Alexander
Zhmurov, Petr
Dar’in, Dmitry
Silonov, Sergey
Kasatkina, Mariia
Zonis, Yulia
Gureev, Maxim
Krasavin, Mikhail
author_facet Safrygin, Alexander
Zhmurov, Petr
Dar’in, Dmitry
Silonov, Sergey
Kasatkina, Mariia
Zonis, Yulia
Gureev, Maxim
Krasavin, Mikhail
author_sort Safrygin, Alexander
collection PubMed
description An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC(50) = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.
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spelling pubmed-84099652021-09-02 Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP) Safrygin, Alexander Zhmurov, Petr Dar’in, Dmitry Silonov, Sergey Kasatkina, Mariia Zonis, Yulia Gureev, Maxim Krasavin, Mikhail J Enzyme Inhib Med Chem Brief Report An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC(50) = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib. Taylor & Francis 2021-08-31 /pmc/articles/PMC8409965/ /pubmed/34461785 http://dx.doi.org/10.1080/14756366.2021.1969386 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Report
Safrygin, Alexander
Zhmurov, Petr
Dar’in, Dmitry
Silonov, Sergey
Kasatkina, Mariia
Zonis, Yulia
Gureev, Maxim
Krasavin, Mikhail
Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title_full Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title_fullStr Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title_full_unstemmed Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title_short Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)
title_sort three-component castagnoli-cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(adp-ribose) polymerase (parp)
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409965/
https://www.ncbi.nlm.nih.gov/pubmed/34461785
http://dx.doi.org/10.1080/14756366.2021.1969386
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