Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents

被引：18

作者：

Akama, Tsutomu ^{[1
]}

Dong, Chen ^{[1
]}

Virtucio, Charlotte ^{[1
]}

Freund, Yvonne R. ^{[1
]}

Chen, Daitao ^{[2
]}

Orr, Matthew D. ^{[2
]}

Jacobs, Robert T. ^{[1
,2
]}

Zhang, Yong-Kang ^{[1
]}

Hernandez, Vincent ^{[1
]}

Liu, Yang ^{[1
]}

Wu, Anne ^{[1
]}

Bu, Wei ^{[1
]}

Liu, Liang ^{[1
]}

Jarnagin, Kurt ^{[1
]}

Plattner, Jacob J. ^{[1
]}

机构：

[1] Anacor Pharmaceut Inc, Palo Alto, CA 94303 USA

[2] SCYNEXIS Inc, Durham, NC 27713 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 21期

关键词：

Benzoxaborole; Structure-activity relationships; Anti-inflammatory; Cytokine; Tumor necrosis factor-alpha; Interleukin-1beta; Interleukin-6; Pharmacokinetics; Collagen-induced arthritis; AFRICAN TRYPANOSOMIASIS; ANTIFUNGAL AGENT; BENZOXABOROLE; INHIBITORS; BORON; INFLAMMATION; PSORIASIS; ARTHRITIS; KINASE; DRUGS;

D O I：

10.1016/j.bmcl.2013.08.096

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-alpha, IL-1 beta, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC50 values between 0.19 and 0.50 mu M, inhibited LPS-induced TNF-alpha and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5870 / 5873

页数：4

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