Imidazole−Dioxolane Compounds as Isozyme-Selective Heme Oxygenase Inhibitors
journal contributionposted on 13.07.2006, 00:00 by Jason Z. Vlahakis, Robert T. Kinobe, Raymond J. Bowers, James F. Brien, Kanji Nakatsu, Walter A. Szarek
Several imidazole−dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include (2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane (1) hydrochloride, are structurally distinct from metalloporphyrin HO inhibitors and lack the aminothiophenol moiety of azalanstat. They were found to be highly selective for the HO-1 isozyme (stress induced) and had substantially less inhibitory potency toward HO-2, the constitutive isozyme. These imidazole−dioxolane compounds are the first of their type known to exhibit this isozyme-selective HO inhibition.