Discovery of Novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole Derivatives as Potential Anti‐Inflammatory Agents. (16th March 2015)

• Record Type: Journal Article
• Authors: Li, Qing; Hu, Qinghua; Wang, Xinning; Zong, Yang; Zhao, Leilei; Xing, Junhao; Zhou, Jinpei; Zhang, Huibin
• Is Part Of: Chemical biology & drug design. Volume 86:Number 4(2015:Oct.)
• Page Start: 509
• Page End: 516
• Publication Date: 2015-03-16
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12513
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12513-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A novel 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative <bold>5</bold> with good anti‐inflammatory activity was identified from our in‐house library. Based on hit compound <bold>5</bold>, two series of 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole derivative <bold>6a</bold>–<bold>g</bold> and <bold>7a</bold>–<bold>h</bold> were designed and synthesized as novel anti‐inflammatory agents. Most of synthesized compounds exhibited good inhibitory activity on NO and TNF‐<italic>α</italic> production in LPS‐stimulated RAW 264.7 macrophages, in which the compound <bold>6e</bold> showed most potent inhibitory activity on NO (IC₅₀ = 0.86 <italic>μ</italic><sc>m</sc>) and TNF‐<italic>α</italic> (IC₅₀ = 1.87 <italic>μ</italic><sc>m</sc>) production. Further evaluation revealed that compound <bold>6e</bold> displayed more potent <italic>in vivo</italic> anti‐inflammatory activity than ibuprofen did on xylene‐induced ear oedema in mice. Additionally, Western blot analysis revealed that compound <bold>6e</bold> could restore phosphorylation level of I<italic>κ</italic>B<italic>α</italic> and protein expression of p65 NF‐<italic>κ</italic>B in LPS‐stimulated RAW 264.7 macrophages.</p> </abstract>