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Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

Five-membered heteroaromatic rings, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. The unique physicochemical properties and biological effects of five-membered he...

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Autores principales: Frühauf, Anton, Behringer, Martin, Meyer-Almes, Franz-Josef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419652/
https://www.ncbi.nlm.nih.gov/pubmed/37570656
http://dx.doi.org/10.3390/molecules28155686
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author Frühauf, Anton
Behringer, Martin
Meyer-Almes, Franz-Josef
author_facet Frühauf, Anton
Behringer, Martin
Meyer-Almes, Franz-Josef
author_sort Frühauf, Anton
collection PubMed
description Five-membered heteroaromatic rings, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. The unique physicochemical properties and biological effects of five-membered heterocycles have positioned them as key structural motifs in numerous clinically effective drugs. Hence, the exploration of five-ring heterocycles remains an important research area in medicinal chemistry, with the aim of discovering new therapeutic agents for various diseases. This review addresses the incorporation of heteroatoms such as nitrogen, oxygen and sulfur into the aromatic ring of these heterocyclic compounds, enhancing their polarity and facilitating both aromatic stacking interactions and the formation of hydrogen bonds. Histone deacetylases are present in numerous multiprotein complexes within the epigenetic machinery and play a central role in various cellular processes. They have emerged as important targets for cancer, neurodegenerative diseases and other therapeutic indications. In histone deacetylase inhibitors (HDACi’s), five-ring heterocycles perform various functions as a zinc-binding group, a linker or head group, contributing to binding activity and selective recognition. This review focuses on providing an up-to-date overview of the different five-membered heterocycles utilized in HDACi motifs, highlighting their biological properties. It summarizes relevant publications from the past decade, offering insights into the recent advancements in this field of research.
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spelling pubmed-104196522023-08-12 Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors Frühauf, Anton Behringer, Martin Meyer-Almes, Franz-Josef Molecules Review Five-membered heteroaromatic rings, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. The unique physicochemical properties and biological effects of five-membered heterocycles have positioned them as key structural motifs in numerous clinically effective drugs. Hence, the exploration of five-ring heterocycles remains an important research area in medicinal chemistry, with the aim of discovering new therapeutic agents for various diseases. This review addresses the incorporation of heteroatoms such as nitrogen, oxygen and sulfur into the aromatic ring of these heterocyclic compounds, enhancing their polarity and facilitating both aromatic stacking interactions and the formation of hydrogen bonds. Histone deacetylases are present in numerous multiprotein complexes within the epigenetic machinery and play a central role in various cellular processes. They have emerged as important targets for cancer, neurodegenerative diseases and other therapeutic indications. In histone deacetylase inhibitors (HDACi’s), five-ring heterocycles perform various functions as a zinc-binding group, a linker or head group, contributing to binding activity and selective recognition. This review focuses on providing an up-to-date overview of the different five-membered heterocycles utilized in HDACi motifs, highlighting their biological properties. It summarizes relevant publications from the past decade, offering insights into the recent advancements in this field of research. MDPI 2023-07-27 /pmc/articles/PMC10419652/ /pubmed/37570656 http://dx.doi.org/10.3390/molecules28155686 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 Review
Frühauf, Anton
Behringer, Martin
Meyer-Almes, Franz-Josef
Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title_full Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title_fullStr Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title_full_unstemmed Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title_short Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors
title_sort significance of five-membered heterocycles in human histone deacetylase inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419652/
https://www.ncbi.nlm.nih.gov/pubmed/37570656
http://dx.doi.org/10.3390/molecules28155686
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