2-Phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives: new potent inhibitors of fMLP-induced neutrophil chemotaxis.
It is well known that both acute and chronic autoimmune inflammatory disorders arise following a breakdown in control of neutrophil activation and recruitment. In the search for new anti-inflammatory agents, we synthesized some new 2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole derivatives and tested them in vitro in order to evaluate their ability to interfere with human neutrophil functions. All tested compounds showed strong inhibition of fMLP-OMe-induced chemotaxis, although they appeared unable to block degranulation and the fMLP-OMe-induced respiratory burst, and were inactive in binding experiments.
Bruno
Olga
O
Dipartimento di Scienze Farmaceutiche, Università di Genova, Genova, Italy. obruno@unige.it <obruno@unige.it>
Brullo
Chiara
C
Bondavalli
Francesco
F
Ranise
Angelo
A
Schenone
Silvia
S
Falzarano
Maria Sofia
MS
Varani
Katia
K
Spisani
Susanna
S
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001667:Binding, Competitive; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D011720:Pyrazoles; D009240:N-Formylmethionine Leucyl-Phenylalanine; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole