%0 Journal Article
%A Roscales García, Silvia
%A Bechmann, Nicole
%A Holger Weiss, Daniel
%A Köckerling, Martin
%A Pietzsch, Jens
%A Kniess, Torsten
%T Novel valdecoxib derivatives by rutheniumIJII) promoted 1,3-dipolar cycloaddition of nitrile  oxides with alkynes– synthesis and COX-2  inhibition activity
%D 2018
%U https://hdl.handle.net/20.500.14352/126384
%X 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.
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