Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent

被引：20

作者：

Honda, Tadashi ^{[1
,2
]}

Dinkova-Kostova, Albena T. ^{[3
,4
]}

David, Emilie ^{[2
]}

Padegimas, Eric M. ^{[2
]}

Sundararajan, Chitra ^{[2
]}

Visnick, Melean ^{[5
]}

Bumeister, Ron ^{[5
]}

Wigley, W. Christian ^{[5
]}

机构：

[1] SUNY Stony Brook, Dept Chem, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA

[2] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA

[3] Univ Dundee, Biomed Res Inst, Dundee DD1 9SY, Scotland

[4] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[5] Reata Pharmaceut Inc, Irving, TX 75063 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 08期

关键词：

Triterpene; Oleanolic acid; Acetylenicimidazole; Inhibitors of nitric oxide production; Inducers of heme oxygenase-1; NQO1; NITRIC-OXIDE PRODUCTION; URSANE TRITERPENOIDS; MOUSE MACROPHAGES; PROTECTION; INHIBITORS; AFLATOXIN; PATHWAYS; OLEANANE; RING;

D O I：

10.1016/j.bmcl.2011.03.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic) imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2188 / 2191

页数：4

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