2-Pyridone-containing heterocycles are considered privileged scaffolds in drug discovery due to their behavior as hydrogen bond donors and/or acceptors and nonpeptidic mimics, and remarkable physicochemical properties such as metabolic stability, solubility in water, and lipophilicity. This review provides a comprehensive overview of multicomponent reactions (MCRs) for the synthesis of 2-pyridone-containing heterocycles. In particular, it covers the articles published from 1999 to date related to anticancer, antibacterial, antifungal, anti-inflammatory, α-glucosidase inhibitor, and cardiotonic activities of 2-pyridone-containing heterocycles obtained exclusively by an MCR. The discussion focuses on bioactivity data, synthetic approaches, plausible reaction mechanisms, and molecular docking simulations to facilitate comparison and underscore the applications of the 2-pyridone motif in drug discovery and medicinal chemistry. We also present our conclusions and outlook for the future.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727751 | PMC |
| http://dx.doi.org/10.1039/d2ra07056a | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioactive 2-pyridone-containing heterocycle syntheses using multicomponent reactions.
RSC Adv
December 2022
Grupo de Catálisis de la UPTC, Escuela de Ciencias Química, Universidad Pedagógica y Tecnológica de Colombia Avenida Central del Norte 39-115 Tunja Colombia
2-Pyridone-containing heterocycles are considered privileged scaffolds in drug discovery due to their behavior as hydrogen bond donors and/or acceptors and nonpeptidic mimics, and remarkable physicochemical properties such as metabolic stability, solubility in water, and lipophilicity. This review provides a comprehensive overview of multicomponent reactions (MCRs) for the synthesis of 2-pyridone-containing heterocycles. In particular, it covers the articles published from 1999 to date related to anticancer, antibacterial, antifungal, anti-inflammatory, α-glucosidase inhibitor, and cardiotonic activities of 2-pyridone-containing heterocycles obtained exclusively by an MCR.
View Article and Find Full Text PDFAzoarene activation for Schmidt-type reaction and mechanistic insights.
Nat Commun
December 2022
School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, 221116, P. R. China.
The Schmidt rearrangement, a reaction that enables C-C or C-H σ bond cleavage and nitrogen insertion across an aldehyde or ketone substrate, is one of the most important and widely used synthetic tools for the installation of amides and nitriles. However, such a reaction frequently requires volatile, potentially explosive, and highly toxic azide reagents as the nitrogen donor, thus limiting its application to some extent. Here, we show a Schmidt-type reaction where aryldiazonium salts act as the nitrogen precursor and in-situ-generated cyclopenta-1,4-dien-1-yl acetates serve as pronucleophiles from gold-catalyzed Nazarov cyclization of 1,3-enyne acetates.
View Article and Find Full Text PDFSynthesis of Functionalized Arylacetamido-2-pyridones through -C(sp)-H-Activated Installation of Olefins and Alkynes.
J Org Chem
July 2020
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India.
We have identified different N-substituted 2-pyridones as inbuilt directing groups for selective C-H-activated functionalization instead of deprotecting and/or throwing away the directing groups. A robust general method for external ligand-free Pd-catalyzed C(sp)-H olefination and alkynylation is established to access valuable phenylacetamido-2-pyridones. Diverse substrate scope has been demonstrated with different examples with high yield and gram-scale synthesis.
View Article and Find Full Text PDFSynthesis of N-Alkenyl 2-Pyridonyl Ethers via a Au(I)-Catalyzed Rearrangement of 2-Propargyloxypyridines.
J Org Chem
October 2016
Department of Chemistry and Biochemistry, Calvin College, 1726 Knollcrest Circle SE, Grand Rapids, Michigan 49546, United States.
N-Alkyl 2-pyridones and other enolizable heterocycles are important synthetic constructs, due to their prevalence in natural products and pharmaceutical targets and their capacity to serve as models for a number of biological and chemical processes. The disclosed Au(I)-catalyzed reaction utilizes 2-propargyloxypyridines to access N-alkylated 2-pyridone products derived from both 5-exo and 6-endo addition of the nitrogen to the pendent alkyne. Experimental and computational studies suggest that the desired 5-exo N-alkenyl 2-pyridonyl ethers are formed reversibly in the transformation.
View Article and Find Full Text PDFStructure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. Part 7: structure-activity studies of bicyclic 2-pyridone-containing peptidomimetics.
Bioorg Med Chem Lett
March 2002
Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., San Diego, CA 92121-1111, USA.
The structure-based design, chemical synthesis, and biological evaluation of bicyclic 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. An optimized compound is shown to exhibit antiviral activity when tested against a variety of HRV serotypes (EC(50)'s ranging from 0.037 to 0.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!