New-pyrazolyl-ureas as potent human neutrophil chemotaxis inhibitors

To increase the potency, particularly in vivo, we planned and synthesized new pyrazole derivatives (compounds 2a-u) modifying the chain in the N1 position of the pyrazole scaffold and introducing more or less lipophilic urea moieties choosen among the most active of previous molecules. All compounds were tested in in vitro chemotaxis assays, in human neutrophils stimulated by 10 nM fMLP-OMe- and 1 nM IL8. Molecules were added to neutrophils 10 min before the incubation step for chemotaxis. The data of antagonism (percentage of activity) were obtained by comparing the chemotactic index, in the absence and in the presence of derivatives. All tested compounds inhibit the fMLP- OMe and the IL8-induced chemotaxis at very low concentration