当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, Synthesis, and Structure-Activity Relationship Study of Novel Indole-2-carboxamide Derivatives as Anti-inflammatory Agents for the Treatment of Sepsis.

Design, Synthesis, and Structure-Activity Relationship Study of Novel Indole-2-carboxamide Derivatives as Anti-inflammatory Agents for the Treatment of Sepsis.

Abstract：

:Sepsis is characterized by a systemic inflammatory response syndrome. Derivatives of indole have been reported to exhibit diverse biological activities. This study reports on the design and synthesis of a new series of indole-2-carboxamide derivatives, which are screened for their anti-inflammatory activities in RAW 264.7 macrophages. A majority of these derivatives effectively inhibited lipopolysaccharides (LPS)-induced expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Preliminary structure-activity relationship analysis was also conducted. The results indicate that the most promising compounds in the prepared series were 14f and 14g. They were found to effectively reduce LPS-induced pulmonary inflammation and overexpression of a series of inflammatory mediators. Furthermore, in vivo administration of 14f and 14g resulted in remarkable lung histopathological improvements in mice without toxicity in organs. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful for further treatment in inflammatory diseases.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Liu Z,Tang L,Zhu H,Xu T,Qiu C,Zheng S,Gu Y,Feng J,Zhang Y,Liang G

doi

10.1021/acs.jmedchem.5b02006

subject

Has Abstract

pub_date

2016-05-26 00:00:00

pages

4637-50

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章

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