The 1H-1,2,3-triazole-originated derivatives of willardiine were obtained by: (i) construction of the 1H-1,2,3-triazole ring in 1,3-dipolar cycloaddition of the uracil-derived azides and the carboxylate-bearing alkynes or α-acylphosphorus ylide, or (ii) N-alkylation of the uracil derivative with the 1H-1,2,3-triazole-4-carboxylate-derived mesylate. The latter method offered: (i) reproducible results, (ii) a significant reduction of amounts of auxiliary materials, (iii) reduction in wastes and (iv) reduction in a number of manual operations required for obtaining the reaction product. Compound 6a exhibited significant binding affinity to hHS1S2I ligand-binding domain of GluR2 receptor (EC = 2.90 µM) and decreased viability of human astrocytoma MOG-G-CCM cells in higher extent than known AMPA antagonist GYKI 52466.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bioorg.2018.10.061 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Reductive sulfinylation by nucleophilic chain isomerization of sulfonylpyridinium.
Nat Commun
January 2025
Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, 210023, Nanjing, China.
Sulfur-containing units are fundamental components widely found in bioactive compounds, prompting notable efforts toward developing synthetic methodologies for incorporating sulfur functionality into organic precursors. The synthesis of sulfinate esters and sulfinamides has garnered significant interest owing to their immense potential for applications, especially in drug development. However, most existing synthetic protocols suffer from some limitations.
View Article and Find Full Text PDFNovel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.
Eur J Med Chem
December 2024
School of Pharmacy and Food Engineering, Wuyi University, 529020, Jiangmen, China; Department of Chemistry, University of Liverpool, L69 7ZD, Liverpool, UK. Electronic address:
Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.
View Article and Find Full Text PDFSmall molecule ATM inhibitors as potential cancer therapy: a patent review (2003-present).
Expert Opin Ther Pat
December 2024
P. Hertsen Moscow Oncology Research Institute, Moscow, Russian Federation.
Introduction: The ataxia telangiectasia mutated kinase (ATM) is key in coordinating the DDR signaling network essential for responding to double-strand breaks (DSBs). Several ATM inhibitors are being investigated for potential anticancer treatment in clinical trials.
Areas Covered: This review aims to provide a comprehensive overview of patents and patent applications since 2003, with a particular focus on the structural properties, activity and efficacy of the claimed ATM kinase small-molecule inhibitors.
Bioisosteric replacement of pyridoxal-5'-phosphate to pyridoxal-5'-tetrazole targeting Bacillus subtilis GabR.
Protein Sci
January 2025
Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois, USA.
Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR.
View Article and Find Full Text PDFSolvent-Dependent Divergent Cyclization of Bicyclo[1.1.0]butanes.
Angew Chem Int Ed Engl
December 2024
Westfälische Wilhelms-Universität Münster: Westfalische Wilhelms-Universitat Munster, Organisch-Chemisches Institut, Corrensstrasse 40, 48149, Münster, GERMANY.
Bicyclo[1.1.0]butanes (BCBs) have recently garnered significant research interest as versatile precursors for synthesizing potential [n.
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!