Roscales García, SilviaBechmann, NicoleHolger Weiss, DanielKöckerling, MartinPietzsch, JensKniess, Torsten2025-11-242025-11-242018Roscales S, Bechmann N, Weiss DH, Köckerling M, Pietzsch J, Kniess T. Novel valdecoxib derivatives by ruthenium(ii)-promoted 1,3-dipolar cycloaddition of nitrile oxides with alkynes – synthesis and COX-2 inhibition activity. Med Chem Commun [Internet]. 2018 [citado 24 de noviembre de 2025];9(3):534-44. Disponible en: https://xlink.rsc.org/?DOI=C7MD00575J10.1039/c7md00575jhttps://hdl.handle.net/20.500.14352/126384Novel valdecoxib-based cyclooxygenase-2 inhibitors were synthesized in one step via 1,3-dipolar cycloaddition of nitrile oxides with a series of eleven aryl alkynes, six of them described for the first time. Application of RuIJII)-catalysis leads preferably to the formation of the 3,4-diaryl-substituted isoxazoles, while under thermal heating with base the 3,5-diaryl substitution pattern is favoured. The new the 3,4-diaryl-substituted isoxazoles possessing a small substituent (H and Me) displayed high COX-2 inhibition affinity (IC50 = 0.042-0.073 μM) and excellent selectivity (COX-2 SI > 2000). In contrast, the 3,5-diaryl substituted compounds displayed almost no COX activity. The introduction of a 4-fluorophenyl substituent resulted in retained high COX-2 affinity, making these compounds together with the feasible one step reaction promising candidates for the development of fluorine-18 labelled radiotracers.engjournal articlehttps://dx.doi.org/10.1039/c7md00575jmetadata only access547Química orgánica (Química)2306 Química Orgánica