Affiliation:
1. Department of Chemical Engineering and Biotechnology, University of Applied Sciences, Haardtring 100, 64295 Darmstadt, Germany
Abstract
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.
Funder
LOEWE Priority Program TRABITA, Hesse, Germany
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference99 articles.
1. Glomb, T., Szymankiewicz, K., and Świątek, P. (2018). Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole. Molecules, 23.
2. Oxadiazoles in Medicinal Chemistry;Hogner;J. Med. Chem.,2012
3. Amide Bond Bioisosteres: Strategies, Synthesis, and Successes;Kumari;J. Med. Chem.,2020
4. Selective Class IIa Histone Deacetylase Inhibition via a Nonchelating Zinc-Binding Group;Lobera;Nat. Chem. Biol.,2013
5. Studies of the Metabolic Stability in Cells of 5-(Trifluoroacetyl)Thiophene-2-Carboxamides and Identification of More Stable Class II Histone Deacetylase (HDAC) Inhibitors;Scarpelli;Bioorg. Med. Chem. Lett.,2008
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