Design and synthesis of tricyclic compounds with enone functionalities in rings A and C: A novel class of highly active inhibitors of nitric oxide production in mouse macrophages

被引：32

作者：

Favaloro, FG

Honda, T ^{[1
]}

Honda, Y

Gribble, GW

Suh, N

Risingsong, R

Sporn, MB

机构：

[1] Dartmouth Coll, Dept Chem, Burke Lab 6128, Hanover, NH 03755 USA

[2] Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 22期

关键词：

D O I：

10.1021/jm025565f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel tricyclic compounds with enone functionalities in rings A and C, which were designed on the basis of the structure of a synthetic triterpenoid, 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid, have been synthesized. Among them, 10 shows high inhibitory activity (IC50 = 1 nM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages and is orally active at 15 mg/kg (once) in a preliminary in vivo study using mouse peritoneal inflammation induced by thioglycollate and interferon-gamma.

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页码：4801 / 4805

页数：5

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