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

Abstract

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-dioxooleana-1,9(11)-dien-28-oic acid, have been synthesized. Among them, 10 shows high inhibitory activity (IC(50) = 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.