Pharmaceutical Importance and Synthetic Strategies for Imidazolidine-2-thione and Imidazole-2-thione Derivatives

Abstract

Imidazole heterocycles containing oxygen or sulfur heteroatoms are of considerable pharmaceutical interest. Many synthetic strategies for imidazolidine-2-thione and imidazole-2-thione derivatives were developed in the past years. They have been well documented by a steadily increasing number of publications and patents. Substituted imidazolidine-2-thiones and imidazole-2-thiones display remarkable biological activities. For instance, imidazole-2-thione has been reported to exhibit antimicrobial, antifungal, antithyroid, antioxidant, cardiotonic, antihypertensive, Dopamine beta-Hydroxylase (DBH) inhibitory and anti-HIV properties. Imidazolidine-2-thione derivatives have been reported to exhibit antimicrobial activity, anti-HIV activity, antifungal activity and so forth. The main purpose of this review is to present a survey of the literature on the different methods of synthesis and reactions involving imidazolidine-2-thione and imidazole-2-thione during the last few decades. This article summarizes an efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted-thiohydantoin, also reported previously. Synthesis of metal complexes of imidazolidine-2-thione and its derivatives were reported as antimicrobial agents also discussed in the article. Some of the chiral imidazolidine-2-thione N-and C-nucleoside were reported as precursors for the synthesis of azidonucleosides and fluoronucleosides known for their anti-AIDS activity. Metal complexes of heterocyclic thione ligands were reported to possess antifungal activity. Imidazolidine-2-thione and imidazole-2-thione derivatives have found applications in diverse therapeutic areas. Imidazolidine-2-thiones are also used as a chiral auxiliary and ligand for asymmetric catalysis.

Synthesis and in vitro antiplatelet aggregation screening of novel fluorinated diethyl-2-(benzylthio)-2,3-dihydro-1H-imidazole-4,5-dicarboxylate derivatives

“…Recent reviews by Dawood and Wahab-Abdel (2010) and Savjani and Gajjar (2011) include a number of synthetic methods that have been employed to synthesise and react these compounds, to produce a wide range of imidazole-2-thiones, substituted at almost all positions on the imidazole-2-thione skeleton. They can be formed from a-bromoketones with substituted hydrazines and potassium thiocyanate (Lagoja et al, 2003), from a-hydroxyketones, thiourea and ammonium thiocyanate (Maduskuie et al, 1995), from benzil and thiourea (Muccioli et al, 2006), from phenylglycine methyl ester with phenyl or alkyl isothiocynate (Muccioli et al, 2006) and from diamines and CS 2 over a zinc oxide/aluminium oxide catalyst (Ballabeni et al, 1999) to name a few.…”

Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity

“…Therefore, this assay provides a more robust knowledge of the efficacy of the inhibitor in the presence of a multitude of proteins. Compound 15 showed considerable inhibition of HTop1 activity in the ex vivo relaxation assays, both under the conditions when the lysates were pre-incubated with the compound 15 ( Figure 3, panel B, lanes [5][6][7][8][9] or added simultaneously ( Figure 3, panel B, lanes [14][15][16][17]. Quantification ( Figure 3, panel C) of the data suggests that compound 15 is potent in inhibiting its target (HTop1) in the midst of a plethora of proteins, corroborating well with the in vitro plasmid relaxation assays (see Figure 1) and is in keeping with the possibility that compound 15 may be a suitable anticancer agent.…”

“…During the last couple of decades, novel hydantoin and thiohydantoin derivatives have received attention in drug discovery due to their diverse pharmaceutical properties and wide range of biological activities [14][15]. Hydantoin derivatives are reported to have anti-cancer [16][17][18], anti-bacterial [19], anti-viral [18] and anti-parasitic [20] activities.…”

Sequential MCR via Staudinger/aza-Wittig versus Cycloaddition Reaction to Access Diversely Functionalized 1-amino-1H-imidazole-2(3H)-thiones

“…Among imidazole derivatives, imidazole-2-thiones have been associated to a special class of biologically relevant thiourea derivatives [6] endowed with antithyroid [7], antiproliferative [8], MPP (Matrix MetalloProteinases) inhibitory [9] property and can be used as building blocks for the synthesis of N-aminoimidazole with antiretroviral activity [10].…”