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

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.

Graphical abstract1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole is a novel semisynthetic triterpenoid whose potency is much higher than the lead compound, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid for inhibition of NO production stimulated with IFN-γ and for induction of the cytoprotective enzymes, NQO1 and HO-1.Figure optionsDownload full-size imageDownload as PowerPoint slide