Potential bioisosteres of β-uracilalanines derived from 1H-1,2,3-triazole-C-carboxylic acids

• Published in: Bioorganic chemistry Vol. 83; pp. 500 - 510
• Main Authors: Mironiuk-Puchalska, Ewa, Buchowicz, Włodzimierz, Grześkowiak, Piotr, Wińska, Patrycja, Wielechowska, Monika, Karatsai, Olena, Rędowicz, Maria Jolanta, Bretner, Maria, Koszytkowska-Stawińska, Mariola
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.03.2019; Elsevier
• Subjects: 1,2,3-Triazoles; Amino acid; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Glioblastoma; Glutamate receptors; Life Sciences & Biomedicine; Nucleobase; Physical Sciences; Science & Technology; Uracilalanine; Willardiine; 1,2,3-Triazoles; Glutamate receptors; Amino acid; Willardiine; Glioblastoma; Uracilalanine; Nucleobase; AMPA; WILLARDIINE DERIVATIVES; RUTHENIUM-CATALYZED CYCLOADDITION; LUMINESCENT LANTHANIDE COMPLEXES; ALPHA-AMINO-ACIDS; MECHANISMS; ORGANIC AZIDES; GLUTAMATE-RECEPTOR; LIGAND; ANTAGONISTS
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.10.061

[Display omitted] 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 (EC50 = 2.90 µM) and decreased viability of human astrocytoma MOG-G-CCM cells in higher extent than known AMPA antagonist GYKI 52466.