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.

Abstract

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.

• Authors: Tadashi Honda, Albena T Dinkova-Kostova, Emilie David, Eric M Padegimas, Chitra Sundararajan, Melean Visnick, Ron Bumeister, W Christian Wigley
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 8 Pg. 2188-91 (Apr 15 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 21441026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-4-ethynylimidazole
• 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole
• Anti-Inflammatory Agents
• Imidazoles
• Nitric Oxide
• Oleanolic Acid
• Interferon-gamma
• Heme Oxygenase-1
• NAD(P)H Dehydrogenase (Quinone)
• Nqo1 protein, mouse

Topics

• Animals
• Anti-Inflammatory Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cytoprotection (drug effects)
• Heme Oxygenase-1 (metabolism)
• Imidazoles (chemical synthesis, chemistry, pharmacology)
• Interferon-gamma (metabolism)
• Mice
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Nitric Oxide (metabolism)
• Oleanolic Acid (analogs & derivatives, chemical synthesis, chemistry, pharmacology)