In this paper the synthesis and the chemotaxis inhibitory activity of a no. of 1H-pyrazole-4-carboxylic acid Et esters 2 functionalized in N1 with a Me group or different hydroxyalkyl chains and in position 5 with a series of 3-substituted urea groups are reported. These compds. were designed as development of previous pyrazole-urea derivs. that resulted potent IL8-induced neutrophil chemotaxis inhibitors in vitro. Most of the new compds. revealed a potent inhibition of both IL8- and fMLP-OMe-stimulated neutrophil chemotaxis. The most active compds. in the fMLP-OMe induced chemotaxis test showed IC50 in the range 0.19 nM-2 μM; a very strong inhibition was obsd. in the IL8-induced chemotaxis test, having the most active compds. IC50 at pM concns. In vivo compds. 2e and 2f, although to a lesser extent, at 50 mg/kg os decreased granulocyte infiltration in zymosan-induced peritonitis in mice.

1-Methyl and 1-(2-hydroxyalkyl)-5-(3-alkyl/cycloalkyl/phenyl/naphthylureido)-1H-pyrazole-4-carboxylic acid ethyl esters as potent human neutrophil chemotaxis inhibitors

BRUNO, OLGA;BRULLO, CHIARA;BONDAVALLI, FRANCESCO;SCHENONE, SILVIA;
2009

Abstract

In this paper the synthesis and the chemotaxis inhibitory activity of a no. of 1H-pyrazole-4-carboxylic acid Et esters 2 functionalized in N1 with a Me group or different hydroxyalkyl chains and in position 5 with a series of 3-substituted urea groups are reported. These compds. were designed as development of previous pyrazole-urea derivs. that resulted potent IL8-induced neutrophil chemotaxis inhibitors in vitro. Most of the new compds. revealed a potent inhibition of both IL8- and fMLP-OMe-stimulated neutrophil chemotaxis. The most active compds. in the fMLP-OMe induced chemotaxis test showed IC50 in the range 0.19 nM-2 μM; a very strong inhibition was obsd. in the IL8-induced chemotaxis test, having the most active compds. IC50 at pM concns. In vivo compds. 2e and 2f, although to a lesser extent, at 50 mg/kg os decreased granulocyte infiltration in zymosan-induced peritonitis in mice.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/267453
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