RT Journal Article
T1 Novel valdecoxib derivatives by rutheniumIJII) promoted 1,3-dipolar cycloaddition of nitrile  oxides with alkynes– synthesis and COX-2  inhibition activity
A1 Roscales García, Silvia
A1 Bechmann, Nicole
A1 Holger Weiss, Daniel
A1 Köckerling, Martin
A1 Pietzsch, Jens
A1 Kniess, Torsten
AB Novel 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.
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/126384
UL https://hdl.handle.net/20.500.14352/126384
LA eng
NO Roscales 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=C7MD00575J
NO Fundación Ramón Areces
NO European Commission-ERC
DS Docta Complutense
RD 20 ene 2026