Heme oxygenase inhibition by 1-aryl-2-(1h-imidazol-1-yl/1h-1,2,4-triazol-1-yl)ethanones and their derivatives

ChemMedChem
Gheorghe RomanWalter A Szarek

Abstract

Previous studies by our research group have been concerned with the design of selective inhibitors of heme oxygenases (HO-1 and HO-2). The majority of these were based on a four-carbon linkage of an azole, usually an imidazole, and an aromatic moiety. In the present study, we designed and synthesized a series of inhibition candidates containing a shorter linkage between these groups, specifically, a series of 1-aryl-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1-yl)ethanones and their derivatives. As regards HO-1 inhibition, the aromatic moieties yielding best results were found to be halogen-substituted residues such as 3-bromophenyl, 4-bromophenyl, and 3,4-dichlorophenyl, or hydrocarbon residues such as 2-naphthyl, 4-biphenyl, 4-benzylphenyl, and 4-(2-phenethyl)phenyl. Among the imidazole-ketones, five (36-39, and 44) were found to be very potent (IC(50)<5 muM) toward both isozymes. Relative to the imidazole-ketones, the series of corresponding triazole-ketones showed four compounds (54, 55, 61, and 62) having a selectivity index >50 in favor of HO-1. In the case of the azole-dioxolanes, two of them (80 and 85), each possessing a 2-naphthyl moiety, were found to be particularly potent and selective HO-1 inhibitors. Three non-carbonyl...Continue Reading

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Citations

Oct 26, 2012·Journal of the Royal Society, Interface·Mona N RahmanZongchao Jia
Jul 19, 2014·European Journal of Medicinal Chemistry·Ute F RöhrigOlivier Michielin
Jan 28, 2012·European Journal of Medicinal Chemistry·Loredana SalernoValeria Sorrenti
Jun 7, 2013·Medicinal Research Reviews·Ling ZhangCheng-He Zhou
Sep 17, 2015·The Journal of Organic Chemistry·Iwona BownikPetr Klán
Aug 10, 2017·Canadian Journal of Physiology and Pharmacology·Maaike HumKanji Nakatsu
Aug 14, 2012·Chemical Biology & Drug Design·Valeria SorrentiLoredana Salerno
May 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Khaled F GreishValeria Pittalà
Sep 25, 2019·European Journal of Medicinal Chemistry·Sebastiano IntagliataGiuseppe Romeo
May 29, 2020·The Journal of Organic Chemistry·Daiki MorikawaKentaro Okano

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