5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens

A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(...

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Autores principales: Rogacheva, Elizaveta, Kraeva, Lyudmila, Lukin, Alexey, Vinogradova, Lyubov, Komarova, Kristina, Chudinov, Mikhail, Gureev, Maxim, Chupakhin, Evgeny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537382/
https://www.ncbi.nlm.nih.gov/pubmed/37764267
http://dx.doi.org/10.3390/molecules28186491
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author Rogacheva, Elizaveta
Kraeva, Lyudmila
Lukin, Alexey
Vinogradova, Lyubov
Komarova, Kristina
Chudinov, Mikhail
Gureev, Maxim
Chupakhin, Evgeny
author_facet Rogacheva, Elizaveta
Kraeva, Lyudmila
Lukin, Alexey
Vinogradova, Lyubov
Komarova, Kristina
Chudinov, Mikhail
Gureev, Maxim
Chupakhin, Evgeny
author_sort Rogacheva, Elizaveta
collection PubMed
description A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c] pyridine (13g), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure–activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico.
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spelling pubmed-105373822023-09-29 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens Rogacheva, Elizaveta Kraeva, Lyudmila Lukin, Alexey Vinogradova, Lyubov Komarova, Kristina Chudinov, Mikhail Gureev, Maxim Chupakhin, Evgeny Molecules Article A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c] pyridine (13g), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure–activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico. MDPI 2023-09-07 /pmc/articles/PMC10537382/ /pubmed/37764267 http://dx.doi.org/10.3390/molecules28186491 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rogacheva, Elizaveta
Kraeva, Lyudmila
Lukin, Alexey
Vinogradova, Lyubov
Komarova, Kristina
Chudinov, Mikhail
Gureev, Maxim
Chupakhin, Evgeny
5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title_full 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title_fullStr 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title_full_unstemmed 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title_short 5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens
title_sort 5-nitrofuran-tagged oxazolyl pyrazolopiperidines: synthesis and activity against eskape pathogens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537382/
https://www.ncbi.nlm.nih.gov/pubmed/37764267
http://dx.doi.org/10.3390/molecules28186491
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