Formyl peptide receptor2 (FPR2) is a G-protein coupled receptor that plays critical roles in inflammatory reactions. FPR2-specific interaction can be possibly used to facilitate the resolution of pathological inflammatory responses by enhancing endogenous anti-inflammation systems. Starting from our lead agonist 5, we designed new ureidopropanamides derivatives able to activate FPR2 in transfected cells and human neutrophils. The new FPR2 agonists showed good stability towards oxidative metabolism in vitro. Moreover, selected compounds showed anti-inflammatory properties in LPS-stimulated rat primary microglial cells. (S)-3-(4-Cyanophenyl)-N-[[1-(3-chloro-4-fluorophenyl)cyclopropyl]methyl]-2-[3-(4-fluorophenyl)ureido]propanamide ((S)-17) emerged as prospective pharmacological tool to study the effects of FPR2 activation in the central nervous system (CNS) being able to reduce IL-1β and TNF-α levels in LPS-stimulated microglial cells and showing good permeation rate in hCMEC/D3 cells, an in vitro model of blood brain barrier. These results are very promising and can open new therapeutic perspectives in the treatment of CNS disorders characterized by neuroinflammation.

甲酰基肽受体2（FPR2）是一种G蛋白偶联受体，在炎症反应中起关键作用。FPR2特异性相互作用可以通过增强内源性抗炎系统来促进病理性炎症反应的解决。从我们的主要激动剂5开始，我们设计了能够激活转染细胞和人类嗜中性粒细胞中FPR2的新型脲基丙酰胺衍生物。新的FPR2激动剂对体外氧化代谢表现出良好的稳定性。此外，选定的化合物在LPS刺激的大鼠原代小胶质细胞中显示出抗炎特性。（S）-3-（4-氰基苯基）-N -[[1-（3-氯-4-氟苯基）环丙基]甲基] -2- [3-（4-氟苯基）脲基]丙酰胺（（S）-17）成为研究FPR2激活在中枢神经系统（CNS）中的作用的前瞻性药理工具，该作用能够降低LPS刺激的小胶质细胞中IL-1β和TNF-α的水平，并在hCMEC中表现出良好的渗透率/ D3细胞，一种血脑屏障的体外模型。这些结果是非常有希望的，并且可以为以神经炎症为特征的中枢神经系统疾病的治疗开辟新的治疗前景。