- 4-PHENYL-1,3-THIAZOLES AND 4-PHENYL-1,3-OXAZOLES DERIVATIVES AS CANNABINOID RECEPTOR LIGANDS
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The present invention relates to new 4-phenyl-1,3-azole derivatives having the general formula (I) wherein R1, R2, R3, R4, X, A, B, and n are variable, in a racemic form, an enantiomeric form or any combinations thereof. These compounds exhibit affinity f
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Page/Page column 22
(2011/04/18)
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- Heme oxygenase inhibition by 1-Aryl-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1- yl)ethanones and their derivatives
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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 (IC5050 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 analogues (87, 89, and 91) of 1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanone were found to be good inhibitors of HO-1. For the first time in our studies, two azole-based inhibitors (37 and 39) were found to exhibit a modest selectivity index in favor of HO-2. The present study has revealed additional candidates based on inhibition of heme oxygenases for potentially useful pharmacological and therapeutic applications.
- Roman, Gheorghe,Vlahakis, Jason Z.,Vukomanovic, Dragic,Nakatsu, Kanji,Szarek, Walter A.
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experimental part
p. 1541 - 1555
(2011/11/29)
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