Abstract
A novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 5 with good anti-inflammatory activity was identified from our in-house library. Based on hit compound 5, two series of 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 6a-g and 7a-h were designed and synthesized as novel anti-inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF-α production in LPS-stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC50 = 0.86 μm) and TNF-α (IC50 = 1.87 μm) production. Further evaluation revealed that compound 6e displayed more potent in vivo anti-inflammatory activity than ibuprofen did on xylene-induced ear oedema in mice. Additionally, Western blot analysis revealed that compound 6e could restore phosphorylation level of IκBα and protein expression of p65 NF-κB in LPS-stimulated RAW 264.7 macrophages.