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A new, one-pot, efficient, and four-component condensation of 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, arylaldehydes and (phenylsulfonyl)acetonitrile in the presence of a reusable basic ionic liquid, 2-hydroxyethylammonium formate, as catalyst for the synthesis of novel 2-(phenylsulfonyl)-1H-benzo[a]pyrano[2,3-c]phenazin-3-amine derivatives under solvent-free conditions at 80 °C was described. A simple reaction and work-up procedure for the synthesis of new un-known compounds using a green and reusable ionic liquid as catalyst under solvent-free and thermal conditions was reported. The easy preparation of ionic liquid was superiority of the mentioned basic ionic liquid. This protocol has various advantages such as short reaction times, excellent yields, no column chromatography, and green environmentally safe media.

In this contribution, we report the design, synthesis and cytotoxicity studies of a series of N-[3-(benzimidazol-2-yl-amino)phenyl]amine and N-[3-(benzoxazol-2-ylamino)phenyl]amine derivatives. In vitro cytotoxicity assay of 26 selected compounds was carried out at National Cancer Institute (NCI), USA. Out of them, compounds 10e (NSC D-762842/1) and 11s (NSC D-764942/1) have shown remarkable cytotoxicity with GI50 values ranging between “0.589–14.3 µM” and “0.276–12.3 µM,” respectively, in the representative nine subpanels of human tumor cell lines. Further, flow cytometry analysis demonstrated that compound 10e exerted cell cycle arrest at G2/M phase and showed dose-dependent enhancement in apoptosis in K-562 leukemia cancer cells.

A deoxyamination methodology of activated and unactivated alcohols is presented. The reaction is mediated by phosphonium intermediates generated in situ from N-haloimides and triphenylphosphine. The protocol allows for the synthesis of phthalimide and amine derivatives in moderate to good yields at room temperature. A series of NMR experiments have provided insight into the reactive intermediates involved and the mechanism of this deoxyamination reaction.

Resistance to bacteria is a growing threat to human health worldwide. The rate of discovery of new antibacterial is far outshined by the rate at which resistance is spreading. Therefore, there remains a pressing need for the development of new antibacterial drugs. Recent alarm estimates that deaths due to antimicrobial resistance may increase from 700,000 million lives annually by 2050. Glucosamine-6-phosphate (GlcN-6-P) synthase represents an interesting protein target because it plays an essential role in the protection of cell wall. The primary aim and objective of this study is to identify lead molecules as promising antibacterial agents by inhibiting Glucosamine-6-phosphate (GlcN-6-P) synthase enzyme. Autodock 4. 2, the effective tool for exploring the binding affinity of small molecule to enzyme target was used to study the interactions between the oxazine derivatives and the GlcN-6-P synthase binding site. The ligands were optimized for improving their efficacy and safety. Lead optimization was performed using Molinspiration server and the ligands were optimized for evaluating their oral bioavailability. With Glucosamine 6 phosphate synthase receptor, the binding energy was found to be best for 5 compounds SZ-3 (-5.27 kcal/mol), SZ-4 (-6.02 kcal/mol), SZ-5 (-5.35 kcal/mol), SZ-8 (-5.62kcal/mol), SZ-10 (-5.29 kcal/mol) when compared to the standard ligand, Ciprofloxacin (-5.09 kcal/mol) and were interacting well with the key residues TYR 304, GLU 438, LEU 484. Docking study strongly enhanced the activity of oxazine derivatives as new discovered hits.

Some of fused dihydrobenzo [4,5]imidazo [1,2-a] pyrmido [5,4-e] pyrmidin-3(4H)-amine derivatives were synthesized, theses derivatives derived from 4-amino-2-(4-chloro or bromophenyl) -1,2-dihydropyrimido[1,2-a] benzimidazole-3-carbonitrile (4,5), which prepared by reaction 1H-benzimidazol-2-amine (1) and p-chlorobenzaldehyde or p-bromobenzaldehyde (2) and malononitrile (3). These derivatives prepared by reaction compound (4,5) with with triethylorthoformate in presence acetic anhydride to give the products (6,7), then the products was reacted with aliphatic amines (hydrazine, methyl amine, ethyl amine, propyl amine and isobutyl amine) to give pyrmidin rings (8-17) respectively. All these derivatives characterization by FT-IR , HNMR spectra and physical properties.

Objective: Benzoxazole derivatives have antifungal, anticancer, antibacterial, and anticonvulsant function. Encouraged by this comment, we agreed to synthesize new Benzoxazole compounds connected to the bases of Schiff's. Methods: 2,4-diaminophenol (1) was prepared by the reaction of 2,4-dinitrophenol and sodium dithionate. Compound (1) reacted with either acetic acid to afford compound (2) or with formic acid to afford compound (3). The Schiff bases were preparation from the reaction condensing reaction of compound (2) or (3) and aromatic aldehydes or ketone; [p-nitrobenzaldehyde, p-hydroxybenzaldehyde, p-chlorobenzaldehyde, p-bromoacetophenone and terephthaldehyde]. Results: FTIR and 1H-NMR spectroscopy characterized all of the preparation compounds. The synthesized derivatives against (Gram positive bacteria GPB) (Bacillus subtilis) and two (Gram-negative bacteria GNB) (Klebsiella pneumoniae and Escherichia coli) and (one fungal species Candida albicans), have been evaluated to their antibacterial activity in vitro. all results showed which most of them have good antibacterial activity, while their antifungal activity revealed that compounds displayed slight antifungal activity. The synthesized Benzoxazole derivatives were docked using, glucosamine 6-phosphate synthase as a ligand. Conclusion: The antimicrobial activity indicates that compounds (4), (7) and (8) have more potent antibacterial activity than the compounds (5) and (6). Molecular docking study revealed that compounds (7) and (8), with bulky phenyl groups are essential to block the active centers of (GluN-6-Ps) amino acids synthase in the bacteria.

New secondary amine derivatives were synthesized by reduction of the corresponding Schiff bases with NaBH4. The reaction conditions were optimized to examine the in situ catalytic activity of the synthesized secondary amines in transfer hydrogenation reactions of substituted acetophenones. In addition, antioxidant activities of all secondary amines were evaluated by the DPPH method in comparison with the activities of the related Schiff bases obtained in previous studies, as well as with BHT and BHA used as positive controls.

The present study aimed to synthesis N-substituted-5-(4-chloroquinolin-2-yl)-1,3,4-thiadiazol-2-amine derivatives. Molecular docking study of the synthesized compounds was carried out. COVID-19 docked with the synthesized compounds and the results indicated that the binding energies of docking 6LU7 with native ligand, and the synthesized compounds were –8.1, –8.0, –7.7, –7.5, –7.4, –7.3, –7.2, –6.7, –6.6, –6.5, and –5.4 kcal/mol. Supplementary Information The online version contains supplementary material available at 10.1134/S1068162021010155.

A practical protocol has been established to access diverse oxazol-2-amine derivatives in one step via the electrochemical desulfurative cyclization of isothiocyanates and α-amino ketones. On the basis of the cycle of in situ generation of iodine/desulfurative cyclization/iodide anion regeneration, the reaction is performed under metal-free and external-oxidant-free electrolytic conditions to achieve the formation of intermolecular C-O and C-N bonds, providing oxazol-2-amines in moderate to excellent yields.

In this study, a series of novel p-menthane type secondary amines (sec-p-menthane-7-amine derivatives 3a–3y) were synthesized and then characterized by FTIR, 1H NMR, 13C NMR, and HRMS. The post-emergence herbicidal activities of these amines against barnyard grass and rape were evaluated by the culture dish method. Most of the sec-p-menthane-7-amine derivatives showed excellent herbicidal activities equivalent to or even higher than either diuron or glyphosate. The alkyl-substituted derivatives were more active than the phenyl-substituted derivatives. The herbicidal activities of compounds 3p, 3r, 3u, and 3w against the root growth of barnyard grass were 404% higher, respectively, than those of glyphosate. The herbicidal activities of compounds 3q, 3v, 3w, and 3x against the root growth of rape were 561%, 494%, 491%, and 544% higher, respectively, than those of diuron, and 484%, 760%, 423%, and 665% higher respectively, than those of diuron against shoot growth of rape. In addition, compounds 3p, 3u, and 3v are almost harmless to rice, wheat, sorghum, maize, and peanuts at a concentration of 100 mg L−1. Most of the compounds are nontoxic to HUVEC-C and BALB/c 3T3 cells. It is indicated that the title compounds could be utilized as botanical herbicides for future weed control.

An organophotocatalyzed C(sp2)–H/N–H cross-dehydrogenative coupling of cyclic aldimines with aliphatic amines has been developed, which represents the first example of visible-light-induced C–H amination of N-sulfonylated imines. This methodology enables the streamline assembly of amine derivatives via radical mediated C–N bond formation. The current protocol features transition-metal-free, mild conditions, good functional group tolerance and good yields.

A direct assembly of secondary benzylureas and related amine derivatives via copper-catalyzed carboamination of styrenes with potassium alkyltrifluoroborates and ureas, anilines, or an amide is reported. Terminal and 1,2-disubstituted alkenes, as well as dienes, participate in this three-component coupling reaction. The reaction mechanism likely involves the addition of an alkyl radical to the styrene, followed by metal-mediated oxidative coupling of the resulting benzylic radical with the amine derivative. Factors that impact substrate reactivity and regioselectivity are discussed.

A novel class of substituted benzo[d]imidazo[5,1-b]thiazol-1-amine derivatives was synthesized utilizing a one-pot Cu-catalyzed cycloaddition of benzothiazole, trichloroacetonitrile, various amines and terminal alkynes in acetonitrile at room temperature. The speed of this simple four-component reaction along with mild conditions, high yields, readily available starting materials, the ease of work-up without using pollutant precious metals–catalysts, and column chromatography are important features of the presented procedure.

The microwave assisted synthesis of 3-Chloro-N-(2-(5-chloro-1-tosyl-1H-benzo [d] imidazol-2-yl) ethyl)-N-substituted quinoxalin-2-amine derivatives is described. 2,3-dichloro quinoxaline (DCQX), as a starting compound and propargyl bromide, as an efficient alkylating agent are used in the synthesis of N-substituted quinoxalin-2-amine derivatives. We realized that microwave assisted synthesis is efficiently replacing conventional method of synthesis.

The present work was aimed to synthesize eight new diphenylamine derivatives by the reactions of 2-chloro-N-(4-(diphenyl amino) thiazol-2-yl)acetamide with substituted phenols in the chloroform along with anhydrous potassium carbonate and potassium iodide. The structures of newly synthesized compounds were characterized by IR, NMR, Mass and elemental analysis techniques. Toxicity profile (acute and subacute oral toxicity) and biological activity (analgesic and anti-inflammatory activity) of the synthesized derivatives was performed. Findings of the present work suggested that the synthesized compounds may be one of the excellent potent compounds to treat pain and inflammation. Therefore compounds of this group especially AK-4 (N-(4-(diphenylamino)thiazol-2-yl)-2-(2- nitrophenoxy)acetamide) could be an excellent starting point to build up new lead compounds in the management of pain and inflammation.

In this research, the synthesis of structurally important antioxidants 7-Hydroxy-4-Methyl Coumarin (C1) and 4- Hydroxy Coumarin derivatives was conducted. Coumarin was modified by various reaction steps for the production of target compounds. Different spectroscopic techniques characterized molecular structures FT-IR ,NMR. Antioxidant activity was carried out against 1,1-diphenyl-2-picrylhydrazyl (DPPH) in vitro spectrophometric assays. Compared to ascorbic acid, all compounds exhibited high antioxidant efficiency. Among compounds, Compound 9 performance was considered to be the highest (92%), followed by compounds 8 and 10 (90%). Ascorbic acid has been used as a standard drug with inhibition of the percentage 90.5%.

A series of N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives with NF-κB inducing kinase (NIK) inhibitory activity were obtained through structure-based drug design and synthetic chemistry. A...

The development of an electrochemically driven, ruthenium-catalyzed C-H hydroxylation reaction of amine-derived substrates bearing tertiary C-H bonds is described. The reaction is performed under constant current electrolysis in a divided cell to afford alcohol products in yields comparable to those of our previously reported process, which requires the use of stoichiometric H

Rheumatoid Arthritis (RA) is an autoimmune disease caused by overproduction of pro-inflammatory cytokines. Janus Kinases (JAKs) mediate cytokines signaling through the Janus Kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways. Clinical studies have shown that Janus kinase 1 (JAK1) mediated signaling plays a key role in synovial response in rheumatoid arthritis. Hence, the inhibition JAK1 is considered as an important therapeutic route for treatment of rheumatoid arthritis. In this study, we have performed three-dimensional quantitative structure-activity relationship (3 D-QSAR), molecular docking, molecular dynamics (MD) and free energy calculations on a series of pyrrolo[2,3-d]pyrimidin-4-amine JAK1 inhibitors. Molecular docking studies of the compounds 03, 13, 36 and 49 with JAK1 were performed to study the binding interactions. The binding conformations of the compounds from docking studies were selected based on binding energy and H-bond interactions and were used as initial structure for MD simulations. Using 3 D-QSAR techniques, a ligand-based comparative molecular field analysis (CoMFA) model (q2 = 0.5, r2 = 0.96) and a receptor-based CoMFA model (q2 = 0.78, r2 = 0.98) were developed. Analysis of the MD results of the most active compound (compound 49) with JAK1 showed the formation of H-bond interactions with residues Glu957, Leu959 and Gly887 and water-mediated H-bond interaction with Gly887 and His885. Based on the contour map analyses of the receptor-based CoMFA, a design strategy was proposed and was used for designing new JAK1 inhibitors. Four of the designed compounds (D57, D58, D98 and D99) showed predicted activity values (pIC50> 8.8) greater than the most active compound for JAK1. MM-PBSA based free energy calculations indicated that the designed compounds were able to form stable binding with JAK1 primarily through electrostatic interactions and van der Waal interactions. Collectively, the outcome of this study can be used to further the progress of JAK1 inhibition for the treatment of rheumatoid arthritis. Communicated by Ramaswamy H. Sarma

A K2CO3 promoted efficient one pot two-step method for the preparation of 1H-imidazol-4- yl-1-amine derivatives has been developed. A series of second amines with an imidazole group were obtained with 56%-91% yields by the K2CO3 promoted amination of acetates and nitrogen deprotection of the imidazole process.

Poly (vinyl chloride) (PVC) was blended with acrylonitrile/diallyl amine derivatives [diallyl amine (DAA), diallyl amine acetate (DAAA), diallyl guanidine (DAGA)] copolymers for the improve...

The present study describes the favourable construction of a crystalline covalent organic framework (COF) with exceptional surface area, tunable pore size and huge CO2 capture efficiency to facilitate a novel multicomponent cyclization by introducing CO2 into extremely reactive organic skeletons. In the presence of a catalytic Cu/CuxOy NP-loaded COF, several 2-bromo-3-alkylacrylic acids combined with several amine derivatives and CO2 (0.1 MPa) are converted to the desired oxazolidinediones in excellent yields (up to 96%) under alkali-free conditions and ambient temperature.

The amide group has one of the most significant functionalities found in many natural products. Herein, low-nucleophilic amides are used in a Mannich-type reaction to synthesize N-acyl-protected amine derivatives. A highly efficient synthetic method utilizing simple aldehydes, N-substituted anilines, and amides as substrates was established through a one-pot amide pathway activated by hydrogen bonding between the ZnCl2 and amide under solvent-free conditions. This strategy can be broadly applied to medicinal chemistry. More importantly, compared with the previous Lewis acid catalyzed reaction, we proposed a new application of zinc chloride.

A wide range of alkyl‐, aryl‐ and heteroarylzinc halides were aminated with highly functionalized alkyl, aryl, and heterocyclic azides. The reaction proceeds smoothly at 50 °C within 1 h in the presence of FeCl3 (0.5 equiv) to furnish the corresponding secondary amines in good yields. This method was extended to peptidic azides and provided the arylated substrates with full retention of configuration. To demonstrate the utility of this reaction, we prepared two amine derivatives of pharmaceutical relevance using this iron‐mediated electrophilic amination as the key step., An azide in need can be an amine indeed: An electrophilic amination of a wide range of alkyl‐, aryl‐, and heteroarylzinc halides with highly functionalized alkyl, aryl, and heterocyclic azides was developed. The reaction proceeds smoothly with FeCl3 (0.5 equiv) as an activator, providing a broad range of highly functionalized secondary amines in good yields.

After being rather neglected as a research field in the past, carbonic anhydrase activators (CAAs) were undoubtedly demonstrated to be useful in diverse pharmaceutical and industrial applications. They also improved the knowledge of the requirements to selectively interact with a CA isoform over the others and confirmed the catalytic mechanism of this class of compounds. Amino acid and amine derivatives were the most explored in in vitro, in vivo and crystallographic studies as CAAs. Most of them were able to activate human or non-human CA isoforms in the nanomolar range, being proposed as therapeutic and industrial tools. Some isoforms are better activated by amino acids than amines derivatives and the stereochemistry may exert a role. Finally, non-human CAs have been very recently tested for activation studies, paving the way to innovative industrial and environmental applications.

In this work, we report the development of Drude polarizable force field parameters for the carboxylate and N-acetyl amine derivatives, extending the functionality of the existing Drude polarizable carbohydrate force field. The force field parameters have been developed in a hierarchical manner, reproducing the quantum mechanical gas-phase properties of small model compounds representing the key functional group in the carbohydrate derivatives, including optimization of the electrostatic and bonded parameters. The optimized parameters were then used to generate the models for carboxylate and N-acetyl amine carbohydrate derivatives. The transferred parameters were further tested and optimized to reproduce crystal geometries and J-coupling data from nuclear magnetic resonance experiments. The parameter development resulted in the incorporation of d-glucuronate, l-iduronate, N-acetyl-d-glucosamine (GlcNAc), and N-acetyl-d-galactosamine (GalNAc) sugars into the Drude polarizable force field. The parameters de...

A facile and versatile synthesis strategy for the bis(1,2,3-triazole) formation reaction was developed from tosylhydrazones and N-amino (N-NH2) azole instead of C-amino amine derivatives. The novel...

A series of new 2-{3-{4-[(5-aryl-1,2,4-oxadiazol-3-yl)methoxy]phenyl}isoxazol-5-yl}-N-(3,4,5-tri-methylphenyl)thiazol-4-amine derivatives is synthesized, and the structures of products are confirmed by 1H and 13C NMR, and mass spectra. The new compounds are tested for their anticancer activity against human cancer cell lines: MCF-7 (breast), A549 (lung), Du-145 (prostate), and MDA MB-231 (breast) by using MTT assay and etoposide as a standard reference. All compounds demonstrate good to moderate activity on all cell lines.

Cyclobutene alcohols undergo Prins cyclisations to generate single diastereomers of novel tricyclic heterocycles with five contiguous stereocentres. The reaction times are significantly shorter (ca. 15 min) than with traditional alkene substrates. Stereoselective aza-Prins cyclisations of cyclobutene amine derivatives give fused aza-heterocyclic scaffolds. Computational studies provide insight into the observed stereocontrol. The modular approach is flexible, enabling the introduction of a variety of functional groups (including amides, nitriles, alkynes, and arenes) into the sp3-rich heterocyclic scaffolds.

Inhibition of MAO-B has been an effective strategy for the treatment of Parkinson’s disease. To find more potent and selective MAO-B inhibitors with novel chemical scaffold, we designed and synthesized a series of new 2,3-dihydro-1H-inden-1-amine derivatives on basis of our previous study. Furthermore, the corresponding structure-activity relationship (SAR) of these compounds is detailedly discussed. Compounds L4 (IC50 = 0.11 μM), L8 (IC50 = 0.18 μM), L16 (IC50 = 0.27 μM) and L17 (IC50 = 0.48 μM) showed similar MAO-B inhibitory activity as Selegiline. Moreover, L4, L16 and L17 also exhibited comparable selectivity with Selegiline, indicating that L4, L16 and L17 could be promising selective MAO-B inhibitors for further study.

A mild, modular, and practical catalytic system for the synthesis of the highly privileged phenethylamine pharmacophore is reported. Using a unique combination of organic catalysts to promote the transfer of electrons and hydrogen atoms, this system performs direct hydroarylation of vinyl amine derivatives with a wide range of aryl halides (including aryl chlorides). This general and highly chemoselective protocol delivers a broad range of arylethylamine products with complete regiocontrol. The utility of this process is highlighted by its scalability and the modular synthesis of an array of bioactive small molecules.

The spectroscopically observed magic-size nanoclusters (ZnSe)34 and (CdTe)34 are isolated as amine derivatives. The nanoclusters [(ZnSe)34(n-octylamine)29±6(di-n-octylamine)5±4] and [(CdTe)34(n-octylamine)4±3(di-n-pentylamine)13±3] are fully characterized by combustion-based elemental analysis, UV–visible spectroscopy, IR spectroscopy, and mass spectrometry. Amine derivatives of both (ZnSe)34 and (CdTe)34 are observed to convert to the corresponding (ZnSe)13 and (CdTe)13 derivatives, indicating that the former are kinetic products and the latter thermodynamic products, under the conditions employed. This conversion process is significantly inhibited in the presence of secondary amines. The isolation of the two new nanocluster derivatives adds to a total of nine of 12 possible isolated derivatives in the (II–VI)13 and (II–VI)34 families (II = Zn, Cd; VI = S, Se, Te), allowing comparisons of their properties. The members of these two families exhibit extensive spectroscopic homologies. In both the (II–VI)13...

Herein, via chemoselective N-mono and N,N-diarylation of an aryl/hetaryl amino amide reaction using benzyne or arynes, an amide-substituted triaryl amine derivative and diaryl amine derivatives were afforded. The scope and limitation of the present study have been studied. The products thus obtained were synthetically transformed to highly functionalized biphenyl bridged heterocycles via Suzuki coupling and condensation with 4,4′-biphenyl dialdehyde. Evaluation of the photophysical properties has revealed that the triaryl amine derivatives are blue emissive with high quantum yields, whereas the heterocyclic triaryl amine derivatives are blue-red emissive. The benzofuran-derived compound 4i was found to be blue emissive with high quantum yield, whereas the pyridine-derived compound 5j was found to be red emissive with low quantum yield.

The complexes [Cu(TPA)Cl]ClO4·½H2O (1-ClO4), [Cu(6-MeTPA)Cl]ClO4/PF6 (2-ClO4/2-PF6), [Cu(6-Me2TPA)Cl]PF6 (3-PF6), [Cu(BPQA)Cl]ClO4/PF6 (4-ClO4/4-PF6), [Cu(BPQA)Cl]ClO4/PF6 (4-ClO4/4-PF6), [Cu(BQPA)Cl]ClO4/PF6 (5-ClO4/PF6), [Cu(L1)Cl]ClO4/PF6 (6-ClO4/6-PF6), [Cu(L2)Cl]ClO4 (7-ClO4) and [Cu(L3)Cl]ClO4 (8-ClO4) have been synthesized and structurally characterized by spectroscopic techniques and single X-ray crystallography. The in vitro cytotoxicity of the prepared Cu(II) complexes was evaluated against A2780 (ovarian), A2780R (cisplatin-resistant variant) and MCF7 (breast cancer) human cancer cell lines. Overall, the complexes revealed significant-to-moderate cytotoxicity, with the best results obtained for the complexes [Cu(BQPA)Cl]ClO4 (5-ClO4) and [Cu(BQPA)Cl]PF6 (5-PF6), showing IC50 values within the range of 4.7–10.8 μM. The ability of the most cytotoxic complexes to cleave DNA under different conditions and the mechanisms underlying this activity were assessed by means of agarose gel electrophoresis.

A highly efficient multi-component one-pot synthesis of novel 1H-imidazo[1,2-a]imidazole-3-amine and imidazo[2,1-c][1,2,4]triazole-5-amine derivatives has been developed through the reaction of easily available aromatic aldehydes, benzoyl cyanide and either 2-aminoimidazole-4,5-dicarbonitrile or 3-amino-1,2,4-triazole in pyridine under controlled microwave heating. The process is environmentally friendly, is operationally simple, with short reaction time and with high yields.

A new series of N,7-diphenyl-7H-benzo[7,8]chromeno[2,3-d]pyrimidin- 8-amine derivatives was synthesized using formic acid as catalyzed and solvent. The structures of new derivatives were confirmed by the spectral data and elemental analyses. Moreover, antimicrobial and antifungal activities has been carryout using S. aureus, S. pyogenes, E. coli, P. aeruginosa, C. albicans, A. niger and drugs nystatin, greseofulvin, ciprofloxacin, chloramphenicol for all the present compounds

In this investigation, eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one and eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine amine derivatives were synthesized based on the novel marine natural product Essramycin. Their anti-epileptic activities were evaluated by 4-aminopyridine (4-AP)-induced hyper excitability model in primary cultured neocortical neurons. Five compounds with [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one skeleton showed remarkable anti-epileptic activities. The preliminary structure-activity relationship (SAR) showed that the pyrimidine-7(4H)-one motif is the necessary "active core" of anti-epileptic activity. To understand the action mechanism of anti-epileptic activity of [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one compounds, docking studies using the model of GABAA as docking scaffolds were performed and the docking results were in concordance with the experiment observations. [Formula: see text].

The oxazole is a well-known five-membered heterocycle containing both oxygen and nitrogen atoms in its structure. The oxazole unit is frequently found in natural products,1 including bengazole A2 a...

The Editor-in-Chief has retracted this article [1] at the request of the corresponding author. Figure 1B appears to be identical to Figure 1D, despite being under different experimental conditions.