Discovery of Novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole Derivatives as Potential Anti-Inflammatory Agents

被引：16

作者：

Li, Qing ^{[1
]}

Hu, Qinghua ^{[2
]}

Wang, Xinning ^{[1
]}

Zong, Yang ^{[1
]}

Zhao, Leilei ^{[1
]}

Xing, Junhao ^{[1
]}

Zhou, Jinpei ^{[3
]}

Zhang, Huibin ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2015年 / 86卷 / 04期

关键词：

2-(piperidin-4-yl)-1H-benzo[d]imidazole derivatives; anti-inflammatory activity; benzimidazole; inflammation; BENZIMIDAZOLE DERIVATIVES; NITRIC-OXIDE; RECEPTOR ANTAGONISTS; BIOLOGICAL-ACTIVITY; THERAPEUTIC USE; INHIBITORS; INFLAMMATION; DESIGN; AGONISTS; DISEASE;

D O I：

10.1111/cbdd.12513

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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- production in LPS-stimulated RAW 264.7 macrophages, in which the compound 6e showed most potent inhibitory activity on NO (IC50=0.86m) and TNF- (IC50=1.87m) 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 IB and protein expression of p65 NF-B in LPS-stimulated RAW 264.7 macrophages.

引用

页码：509 / 516

页数：8

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