title: 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: Department of Chemistry, Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook, Stony Brook, NY 11794, USA. tadashi.honda@stonybrook.edu
authors: Tadashi
authors: T
authors: Honda
authors: Albena T
authors: AT
authors: Dinkova-Kostova
authors: Emilie
authors: E
authors: David
authors: Eric M
authors: EM
authors: Padegimas
authors: Chitra
authors: C
authors: Sundararajan
authors: Melean
authors: M
authors: Visnick
authors: Ron
authors: R
authors: Bumeister
authors: W
authors: W
authors: Christian Wigley
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C559482:1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-4-ethynylimidazole; C472829:1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole; D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D009569:Nitric Oxide; D009828:Oleanolic Acid; D007371:Interferon-gamma; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse