Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, viale Benedetto XV, 3, 16132 Genova, Italy.
Eur J Med Chem. 2012 Jan;47(1):573-9. doi: 10.1016/j.ejmech.2011.11.031. Epub 2011 Nov 25.
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.
中性粒细胞募集的异常激活是许多炎症性疾病的原因之一。趋化因子 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和白细胞介素 8（IL8）分别在中性粒细胞趋化作用的后期和早期阶段发挥关键作用，可能通过两种独立的机制。我们在这里报道了新的 N-芳基-2-苯基-2,3-二氢-咪唑并[1,2-b]吡唑-1-甲酰胺 7-取代物的合成和生物学评价，这些化合物被设计为可能的多靶点抗炎药物。许多标题化合物对人中性粒细胞趋化性表现出良好的抑制作用，抑制范围为纳摩尔级，对 fMLP-OMe（fMLP 的甲酯）或 IL8 刺激具有选择性；而两种化合物表现出有趣的双重活性，可在纳摩尔浓度下抑制 fMLP-OMe 和 IL8 诱导的趋化作用。
