Modified Bucherer—Bergs Reaction for the One‐Pot Synthesis of 5,5′‐Disubstituted Hydantoins from Nitriles and Organometallic Reagents.

Montagne, Cyril; Shipman, Michael

doi:10.1002/chin.200650139

Cited by 4 publications

(5 citation statements)

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“…The 2-thiohydantoin ring has been also incorporated into the structures of several natural products such as Enzalutamide, which has been FDA-approved as a drug for castration-resistant prostate cancer ( Figure 1 ) [ 25 , 26 , 27 ]. Based on the high therapeutical significance of the 2-thiohydantoin-based compounds, the synthesis of a novel class of substituted-2-thiohydantoins has attracted great attention in recent decades [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

et al. 2022

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Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.

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Section: Introductionmentioning

confidence: 99%

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

et al. 2022

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“…The studies have aimed to develop efficient MCR protocols for the generation of a series of heterocyclic compounds. MCRs such as the Strecker synthesis [12], Hantzsch synthesis [13], Biginelli synthesis [14], Mannich reaction [15], Kabachnik-Fields reaction [16], Bucherer-Bergs reaction [17], Gewald reaction [18], Willgerodt-Kindler reaction [19], Ugi reaction [20] and A3 coupling [21] are named reactions which include the carbonyl compounds as one of the reactants. The synthetic arylation via transition metal-free conditions [22] and synthesis of a series of unreported N-fused heterocycles [23,24] was reported by our group.…”

Section: Introductionmentioning

confidence: 99%

A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies

et al. 2016

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This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b]indazole analogues. Response Surface Methodology (RSM) coupled with a Box-Behnken design (BBD) were utilized for exploring the effect of base used (A), temperature of reaction (B) and (C), reaction time. This approach can allow access to a variety of pyrimidoindazole fluorophores and related compounds. The compound N,N-dimethyl-4-(2-phenylpyrimido[1,2-b]indazol-4-yl)aniline (4e) displays the maximum fluorescence intensity at 518 nm and shows a fluorescence quantum yield of 0.068. The synthesized pyramido-fused indazoles have been evaluated for their free radical scavenging activity and compound 4f showed good antioxidant activity.

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“…A recently reported [ 87 ] modified Bucherer–Bergs reaction is based on the reaction of a nitrile with an organometallic reagent such as RMgX or RLi to generate an intermediate imine, which in a subsequent reaction with KCN and (NH 4 ) 2 CO 3 affords the corresponding hydantoin ( Scheme 33 ). This method is practical for the one-pot synthesis of 5,5-disubstituted hydantoins and the preferential selection of this strategy should be based on the following: (i) a very large number of nitriles are commercially available or readily accessible; (ii) a variety of common organometallic reagents including RMgX and RLi add to alkyl-, aryl- and heteroaryl-substituted nitriles in high yields; (iii) protonation of the intermediate metallated imine directly leads to the NH imine, an intermediate in the Bucherer–Bergs reaction.…”

Section: Comparison With Other Methods Affording Hydantoinsmentioning

confidence: 99%

“…Most commonly, a mixture of one of these alcohols with water is used. It was established [ 87 ] that THF is also tolerated in the Bucherer–Bergs reaction but only at low concentrations in solvent mixtures with water and ethanol. The experiments performed on n -butyl phenyl ketone (1 mmol scale) under a standard set of reaction conditions (three equiv.…”

Section: Scope and Limitationsmentioning

confidence: 99%

The Bucherer–Bergs Multicomponent Synthesis of Hydantoins—Excellence in Simplicity

et al. 2021

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Hydantoins and their hybrids with other molecules represent a very important group of heterocycles because they exhibit diverse biological and pharmacological activities in medicinal and agrochemical applications. They also serve as key precursors in the chemical or enzymatic synthesis of significant nonnatural α-amino acids and their conjugates with medical potential. This review provides a comprehensive treatment of the synthesis of hydantoins via the Bucherer–Bergs reaction including the Hoyer modification but limited to free carbonyl compounds or carbonyl compounds protected as acetals (ketals) and cyanohydrins used as starting reaction components. In this respect, the Bucherer–Bergs reaction provides an efficient and simple method in the synthesis of important natural products as well as for the preparation of new organic compounds applicable as potential therapeutics. The scope and limitations, as well as a comparison with some other methods for preparing hydantoins, are also discussed.

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Modified Bucherer—Bergs Reaction for the One‐Pot Synthesis of 5,5′‐Disubstituted Hydantoins from Nitriles and Organometallic Reagents.

Cited by 4 publications

References 0 publications

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies

The Bucherer–Bergs Multicomponent Synthesis of Hydantoins—Excellence in Simplicity

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