N-Aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted strongly inhibiting both fMLP-OMe- and IL-8-induced human neutrophil chemotaxis

Anomalous activation of neutrophil recruitment is one of the causes of many inflammatory diseases. The chemoattractants N-formyl-methionyl-leucyl-phenylalanine (fMLP), and interleukine 8 (IL8) play a pivotal role in neutrophil chemotaxis regulation in the latter and early stages, respectively, probably by two independent mechanisms. We reported here synthesis and biological evaluation of new N-aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted which were designed as possible multi-target antiinflammatory agents. Many of the title compounds showed a good inhibition, in the nano molar range, of human neutrophil chemotaxis selectively acting toward fMLP-OMe (methylester of fMLP) or IL8 stimulus; whereas, two compounds showed an interesting dual activity inhibiting both fMLP-OMe and IL8-induced chemotaxis at nano molar concentration.

New N-aryl-2-phenyl-2,3-dihydro-imidazo[1,2-b]pyrazole-1-carboxamides 7-substituted able to inhibit at nanomolar concentration both fMLP-OMe- and IL8-induced neutrophil chemotaxis.Figure optionsDownload as PowerPoint slideHighlights
► Title compounds are potent fMLP-OMe and IL8 neutrophils chemotaxis inhibitors.
► Lack of substituents in position 7 give selective inhibitors toward fMLP-OMe.
► Two compounds showed an interesting dual activity toward both the chemoattractants.