Enaminone Derivatives Research Articles

New enaminone derivatives of 6-hydroxy-4,7-dimethoxy-benzofuran-5-yl scaffold: Synthesis, antimicrobial and antioxidant activities, and molecular docking studies as potential DNA gyrase B and DHFR inhibitors

New enaminone derivatives of 6-hydroxy-4,7-dimethoxy-benzofuran-5-yl scaffold: Synthesis, antimicrobial and antioxidant activities, and molecular docking studies as potential DNA gyrase B and DHFR inhibitors

Synthesis, molecular modelling and choline esterase enzyme inhibitory activity of novel enaminone derivatives of sulfonamides

Synthesis, molecular modelling and choline esterase enzyme inhibitory activity of novel enaminone derivatives of sulfonamides

The most Recent Compilation of Reactions of Enaminone Derivatives with various Amine Derivatives to Generate Biologically Active Compounds.

Heterocyclic derivatives serve as the fundamental components of both natural and synthetic drugs. Enaminones play a crucial role as foundational units in the synthesis of numerous bioactive heterocyclic compounds, including pyrazoles, pyridines, oxazoles, isoxazoles, as well as fused heterocyclic structures like indoles, carbazoles, quinolines, acridines, and phenanthridines. These diverse heterocyclic rings are well-known for their various therapeutic activities, encompassing anticancer, anti-inflammatory, antimicrobial, antidepressant, and antiviral properties. By reacting with nitrogenbased nucleophiles, enaminones can generate bioactive azoles, azines, and their fused systems. This study focuses on the recent advancements in enaminone reactions with (a) nitrogen-based nucleophiles, such as aliphatic amines, derivatives of aniline, heterocyclic amines, hydroxylamine, hydrazine derivatives, guanidine derivatives, urea, and thiourea derivatives, and (b) nitrogen-based electrophiles, such as diazonium salts. These reactions have led to the synthesis of a wide range of bioactive fused heterocyclic compounds from 2010 to the end of 2022.

A Holistic Review of 3-Dimethylamino-1-Arylpropenones Based Disperse Dyes for Dyeing Polyester Fabrics: Synthesis, Characterization, and Antimicrobial Activities.

The enaminone compounds 3-Dimethylamino-1-arylpropenones produced in this review was synthesized by reacting para-methylacetophenone and para-nitroacetophenone with dimethylformamide dimethyl acetal. In this review article, we discuss how to create novel disperse colors by reacting enaminone derivatives 3a and 3b with phenyldiazonium salt. The highly productive procedure of creating new disperse dyes was followed by the process of dyeing polyester fabrics at temperatures between 70 and 130 °C. As a result, the colours' resistance to light, rubbing, perspiration, and washing fastness was assessed. In an effort to show the additional value of these dyes, the expected biological activity of the synthetic dyes against fungus, yeast, and Gram-positive and Gram-negative bacteria was also assessed. We have applied zinc oxide nanoparticles for polyester fabrics treatment to impact them a self-cleaning quality, increase their light fastness, enhance their antibacterial efficacy, and enhance UV protection as part of our ongoing strategy to obtain polyester fabrics with newly acquired specifications.

Bioactivity of benzophenazine enaminone derivatives as inhibitors of ERK2 based on molecular docking and dynamics simulation studies

Molecular docking is a commonly employed technique in structure-based drug design that generates the binding pose and affinity between ligands and targets.

Synthesis of some o-Hidroksi Enaminone Derivatives and Cyclohexadiene by Tandem Oxidative-Reaction in Tetrachloro-1,4-benzoquinone (TCB) Medium

Bu çalışmada 7 adet orjinal o-hidroksi aril enaminon ile siklohekzadienin türevleri TCB ortamında tandem reaksiyonu ile sentezlenip, yapıları 1H NMR, 13C NMR ve HR-MS spektroskopisi aydınlatılmıştır. Ayrıca, bu reaksiyon oxidatif birleşme ve molekül içi halkalaşma tepkimesini içermektedir. Kromonlar, doğal olarak oluşan bileşiklerden meydana gelen bir gruptur. Doğada, özellikle bitkilerin bileşenleri içerisinde bulunur. Halkalı kromonların yaygın olarak doğal biyolojik aktif özelliklere sahip olmasından dolayı, literatüre giren her kromon türevlerinin sentezi literatüre önemli katkı yapacağı düşünülmektedir. Bu çalışmada sentezlenen söz konusu bileşiklerin yüzdesel verimleri oldukça yüksek değerlere sahip olup, oda sıcaklığında ılımlı şartlarda gerçekleştirilmiştir.

Structural, spectroscopic, quantum chemical, and molecular docking study towards cartilage protein of (3E,3′E)-3,3′-(1,4-phenylenebis(azanediyl))bis(cyclohex-2-en-1-one)

This article presents the results of the structural and spectroscopic analysis of (3E,3′E)-3,3′-(1,4-phenylenebis(azanediyl))bis(cyclohex-2-en-1-one) by the means of IR, Raman, NMR, and Density functional theory methods. The structure of the compound was optimized at the B3LYP/6-311++G(d,p) level of theory. The NMR spectra were predicted using the Gauge Independent Atomic Orbital approach. The mean absolute differences between experimental and theoretical chemical shifts were 0.44 and 2.3 ppm for 1H and 13C NMR spectra thus proving the applicability of the chosen level of theory. The vibrational (IR and Raman) spectra were assigned based on the optimized structure following the Potential Energy Distribution (PED) analysis. The intermolecular interactions governing the stability of the compound were investigated by the Natural Bond Orbital and Quantum Theory of Atoms in Molecules analyses. The active positions in the compound were assessed by the Fukui functions calculation and Molecular electrostatic potential map. The inhibitory activity of the compound was analyzed by molecular docking toward cartilage proteins. This activity, along with the groups included in interactions, proved the activity of various parts of the molecule. The inhibitory activity was higher than that of a native ligand. The ecotoxicity assessment proved low toxicity towards aquatic organisms. These results show the high potential of enaminone derivatives obtained under mild conditions.

KI-TBHP mediated cascade oxidative annulations of enaminones: A facile approach towards 2, 4, 5-Trisubstituted oxazoles

A practical and efficient method for the construction of poly substituted oxazoles has been developed using a catalytic amount of potassium iodide and TBHP as the green oxidant via amidation followed by intramolecular oxidative cyclization of enaminone derivatives under mild reaction conditions. The attracting feature is oxidation of benzylic C–H bond and dehydrogenation of enaminone occurred in one pot under base free conditions.

Design and development of trifluoromethylated enaminone derivatives as potential anticonvulsants

Enaminone derivatives have been widely studied as potential anticonvulsant agents to treat epilepsy. Our research group is focused on evaluating the anticonvulsant activities of cyclic enaminones connected to a substituted aromatic ring via a sp2 hybridized linker. We herein report our lead optimization efforts and the subsequent synthesis of the target fluorinated N-benzamide enaminone analog N-(3-oxo-5-(trifluoromethyl) cyclohex-1-en-1-yl)-4-(trifluoromethyl) benzamide (compound 7) from fluorinated intermediates, and its bioevaluation in acute seizure rodent models. The synthesis of the fluorinated cycloalkyl intermediates, 5-(trifluoromethyl) cyclohexane-1,3-dione (compound 5) and 3-amino-5-(trifluoromethyl) cyclohex-2-en-1-one (compound 6) were derived from an improve method of a one-pot hydrolysis and acid catalyzed decarboxylation of 4-carbo-tert-butoxy-5-trifluoromethylcyclohexane-1,3-dione (compound 4). Compound 7 produced pharmacological response at a higher dose of 300 mg/kg with only 25% protection observed, when compared to our previous lead compound THA40 in the 6 Hz 44 mA animal model. In the maximal electroshock (MES) model, compound 7 showed moderate activity at 100 mg/kg with 25% after 2 h. At a higher dose of 300 mg/kg, 25% of the animals were protected both at 0.5 h and 2 h. Although compound 7 did not produce the expected results, it allowed for a new avenue to investigate during our lead optimization studies.

Synthesis, characterization, and antimicrobial activity investigations of ruthenium (II)–bipyridine complexes of ciprofloxacin derivatives

AbstractA series of ruthenium (II) complexes derived from the reaction between cis‐bis (2,2′‐bipyridine) dichloro ruthenium (II) dihydrate and enaminone derivatives of ciprofloxacin were synthesized and fully characterized using elemental analysis, cyclic voltammetry and different spectroscopic techniques (Uv–vis, FTIR, NMR, mass spectroscopy, and X‐ray photoelectron spectrometry (XPS)). The isolated compounds were tested for their antibacterial and antifungal activities against gram‐negative and gram‐positive bacteria. The FTIR data revealed that ciprofloxacin derivatives act as bidentate ligands through the pyridone carbonyl and the carboxylate oxygen atom. The UV–visible data showed that the charge transfer CT band is blue shifted upon the coordination of the ciprofloxacin derivatives compared to the CT band of the parent complex. The XPS results revealed the characteristic peaks of Ru3p3/2and Ru3p1/2as well as Ru3d5/2and Ru3d3/2, which confirmed the assembly of the ruthenium (II) ciprofloxacin derivative complexes. Cyclic voltammetry data showed that the ciprofloxacin enaminone derivatives have a similar reduction potential for the Ru (II)/Ru (III) redox couple, and it revealed that the coordination of the ruthenium (II) ion altered the redox property of the ligands and enhanced their electron transfer rate. The electrochemical and the UV–visible results suggest that the ciprofloxacin derivative ligands are‐acceptor ligands. Further, the complexes showed higher antibacterial activities than the parent ciprofloxacin antibiotic and did not show antifungal activities among the tested fungi strains.

Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent ciprofloxacin derivatives

Development of new derivatives of commercial antibiotics using different organic reagents and testing these derivatives against different microorganisms are the main goals of this article. Thus, the antibiotic ciprofloxacin, CF, was acylated via reaction with ethyl cyanoacetate and ethyl acetoacetate in basic medium to give the cyanoacetylpiprazinyl dihydroquinoline derivative 3, and oxobutanoylpiprazinyl dihydroquinoline derivative 5, respectively. On the other hand, N-alkylated derivatives 8–10, were prepared through the reaction of CF with chloroacetonitrile, chloroacetyl acetone and chloroacetone in the presence of carbonate salt. In basic medium, both 3 and 10 were coupled with benzenediazonium chloride to afford hydrazono derivatives, which were then cyclized to give 4-(dihydropyridazinecarbonyl)piperazinyl-1,4-dihydroquinoline. Furthermore, compounds 3 and 10 were reacted with benylidenemalononitrile to produce 4H-pyan and pyrido[1,2-a]pyrazine derivatives, respectively. Both 3 and 10 were reacted with DMFDMA to give enaminone derivatives. These enaminones were cyclized to aminopyrimidine derivatives by reacting with urea or thiourea. X-ray, elemental analysis and spectral data were used to illustrate and confirm the structures of the isolated compounds. The bioactivities of the novel compounds were investigated against different gram-positive and gram-negative bacteria. In addition, these novel antibiotic derivatives were tested against ciprofloxacin-resistant bacteria isolated from patients aged 65–74 years. This study reveals that most of the modified drugs show high to moderate antibacterial activity. Additionally, these drugs show good effects against ciprofloxacin-resistant bacteria.

Green synthesis of new lawsone enaminones and theirZ/E(CC)-isomerization induced by organic solvent

The synthesis of a new class of lawsone enaminone derivatives by using lawsone, triethyl orthoformate and aromatic amines in the presence of guanidinium chloride under solvent-free conditions has been developed.

Synthesis, Characterization, Molecular Docking and Enzyme Inhibition Studies of Some Novel Enaminone Derivatives and Their Complexes with Cu(II), Cd(II) and Co(II) Ions

Two new enaminone ligands, 3-chloro-4-{(4-chlorophenyl)amino}pent-3-en-2-one (Ac-PCA), 4-(benzylamino)-3-chloropent-3-en-2-one (Ac-BA) and their metal complexes with transition metal ions [Cu(II), Cd(II) and Co(II)] were prepared and subsequently characterized by FTIR, ICP-AES, UV-Vis, TGA, 1H NMR, 13C NMR and FAB-MS. These newly synthesized compounds were further investigated for anti-acetylcholinesterase (AChE) and anti-urease activities. The (Ac-BA)Cu(II) complex exhibited good anti-AChE while (Ac-BA)2Co(II) complex was potent against anti-urease activities. Other ligands and complexes showed poor to no enzyme inhibitory activities. The synthesized compounds were docked inside acetylcholinesterase enzymes to determine their putative binding mode.

Synthesis, Characterization, Molecular Docking and Enzyme Inhibition Studies of Some Novel Enaminone Derivatives and Their Complexes with Cu(II), Cd(II) and Co(II) Ions

Two new enaminone ligands, 3-chloro-4-{(4-chlorophenyl)amino}pent-3-en-2-one (Ac-PCA), 4-(benzylamino)-3-chloropent-3-en-2-one (Ac-BA) and their metal complexes with transition metal ions were prepared and subsequently characterized by FTIR, ICP-AES, UV-Vis, TGA, 1H NMR, 13C NMR and FAB-MS. These newly synthesized compounds were further investigated for anti-acetylcholinesterase (AChE) and anti-urease activities. The (Ac-BA)Cu(II) complex exhibited good anti-AChE while (Ac-BA)2Co(II) complex was potent against anti-urease activities. Other ligands and complexes showed poor to no enzyme inhibitory activities. The synthesized compounds were docked inside acetylcholinesterase enzymes to determine their putative binding mode. Keywords: Antiureas activity, enaminone, metal complexes, acetylcholinesterase inhibition studies

Synthesis and Characterization of Enaminone Derivatives of Barbituric Acid

In this study, four enaminones derived from barbituric acid were synthesized with the reaction of 5-formylbarbituric acid and selected primer amines with high yield. The structures of allcompounds were proved by using ATR-FTIR, 1H and 13C NMR spectroscopy. Also, 19F NMR spectroscopy was used for characterization of 2d. The obtained spectroscopic results have compliedwith reported similar derivatives in literature.

Aggregation‐Induced Emission of Highly Planar Enaminone Derivatives: Unexpected Fluorescence Enhancement by Bromine Substitution

AbstractUnlike typical aggregation‐induced‐emission (AIE) molecules with twist/rotor structures, two AIE‐active enaminone derivatives with highly planar conformations are herein reported. Interestingly, the bromine‐substituted enaminone fluorophore (BrE) exhibits unexpected stronger emission in solid states than unsubstituted enaminone fluorophore (HE), which is seldom observed for organic fluorophores. Remarkably, the fluorescence quantum efficiency of BrE crystal is ten times as large as that of HE crystal. Based on single‐crystal analysis and theoretical calculation, the unusual fluorescence behavior is attributed to the important effect of bromide substituents which not only form intermolecular Br⋅⋅⋅Br halogen bonding to block nonradiative relaxation pathways efficiently but also promote the radiative process.

Design, synthesis and anticonvulsant evaluation of fluorinated benzyl amino enaminones.

Inspite of progress made for the discovery of novel antiepileptic drugs, epilepsy remains an unmet medical need. We synthesized nine trifluoromethylated enaminone derivatives and tested them for their anticonvulsant activity using maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and rotorod test for neurotoxicity. Among the compounds tested 3-(4-fluoro-3-(trifluomethyl)benzylamino)-5-(trifluoromethyl)cyclohex-2-enone (4f) showed ED50 of 23.47 mg/kg, when given orally to rats, 3-(4-chlorophenylamino)-5-(trifluoromethyl)cyclohex-2-enone (5a), which was previously reported by us but for which no quantitative data was available at the time, exhibited an ED50 of 62.39 mg/kg. Under the same conditions commercially available carbamazepine showed an ED50 of 28.20 mg/kg. There were no neurotoxicity observed upto a dose of 300 mg/kg for all the tested compounds. Compounds 4f and 5a represent good lead compounds for further development.

SYNTHESIS OF SOME ENAMINONE DERIVATIVES UNDER SOLVENT-FREE PROCESS

The reaction of β-diketones with DMF-DMA produces substituted enamines 15 used for the preparation of enaminones 17 under solvent-free conditions. All of enaminone derivatives present a trans conformation. This strategy is highly viable for future applications for the synthesis of thiazolidinone derivatives.

Preparation of 2,4,5-Trisubstituted Oxazoles through Iodine-mediated Aerobic Oxidative Cyclization of Enaminones.

A novel approach to trisubstituted oxazoles has been developed that is based upon an iodine-mediated aerobic oxidative cyclization of enaminone derivatives. This transition-metal-free procedure was highly efficient and involved the removal of four hydrogen atoms under mild conditions.

Fabrication of Nano‐CuO@ZnO for the Synthesis of Functionalized β‐Enaminone Derivatives from β‐Nitrostyrenes, Aliphatic/Aromatic Amines and 1,3‐Dicarbonyl/4‐Hydroxy Coumarin

AbstractHere, we have reported synthesis, characterization of CuO doped ZnO nanoparticles (CuO@ZnO NPs) and its applications for the synthesis of functionalized β‐enaminone derivatives via one‐pot three component reactions of β‐nitrostyrenes, aliphatic/aromatic amines or alcohols and 5,5‐dimethylcyclohexane‐1,3‐dione/4‐hydroxycoumarin. The present CuO@ZnO NPs‐catalyzed sustainable protocol has enabled access to variety of β‐enaminone derivatives in moderate to excellent yields (61‐96%) in comparatively short reaction time periods (2‐3 h). The catalyst was found to be very stable under the reaction conditions and easily recovered from reaction mixture by filtration and recycled for at least ten times without significant loss in its catalytic efficiency.