Heme oxygenase inhibition by 2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes: Effect of halogen substitution in the phenyl ring

Journal Publication ResearchOnline@JCU
Roman, Gheorghe;Riley, John;Vlahakis, Jason;Kinobe, Robert;Brien, James;Nakatsu, Kanji;Szarek, Walter
Abstract

A series of 2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes comprising imidazole–ketones, imidazole–dioxolanes, and imidazole–alcohols substituted with halogens in the phenyl ring were synthesized and evaluated as novel inhibitors of heme oxygenase which are structurally distinct from metalloporphyrins. The entire library of compounds was found to be highly active, with the bromine- and iodine-substituted derivatives being the most potent. The imidazole–dioxolanes were all selective for the HO-1 isozyme (inducible) and exhibited substantially lower activity toward the HO-2 isozyme (constitutive). The corresponding imidazole–ketones and imidazole–alcohols showed selectivity toward HO-1 to a lesser degree than the similarly substituted imidazole–dioxolanes.

Journal

BIOORGANIC & MEDICINAL CHEMISTRY

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Volume

15

ISBN/ISSN

1464-3391

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Pages Count

10

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Publisher

Elsevier

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DOI

10.1016/j.bmc.2007.02.034