Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents |
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| Authors: | Xinning Wang Yang Zong Leilei Zhao Junhao Xing Jinpei Zhou Huibin Zhang |
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| Affiliation: | 1. Center of Drug Discovery, China Pharmaceutical University, Nanjing, China;2. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China;3. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China |
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| Abstract: | A novel 2‐(piperidin‐4‐yl)‐1H‐benzod]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‐benzod]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. |
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| Keywords: | 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivatives anti‐inflammatory activity benzimidazole inflammation |
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