Volume 28, Issue 1

In this study, we evaluated the performance of nano-γ-Fe 2 O 3 –SO 3 H catalyst in the Biginelli reaction and synthesized 3,4-dihydropyrimidine-2-(1 H )-ones. This reaction was carried out under solvent-free and ultrasonic irradiation conditions and belonged to one-pot multicomponent reactions (MCRs) with an adopted aromatic aldehyde, ethyl acetoacetate, and urea as starting materials for the beginning of the reaction. The synthesized materials were efficient in synthesizing 3,4-dihydropyrimidine-2-(1 H )-ones via the Biginelli reaction under reaction conditions. Thus, the advantages of using nano-γ-Fe 2 O 3 –SO 3 H in the Biginelli reaction are short reaction time, high efficiency, green method, solvent free, and cost-effective. Furthermore, nano-γ-Fe 2 O 3 –SO 3 H as a heterogeneous catalyst can be recycled five times without significantly reducing catalytic activity. Graphical abstract

This research investigated the general high-throughput synthetic protocol for the accelerated synthesis of functionalized trifluoromethylpyrazolopyrimidines 3 and N -(5-cyano-3-methyl-1-phenyl-1 H -pyrazol-4-yl) benzamide 4 from aminocyanopyrazole 1 precursors. The action of chlorosulfonyl isocyanate (CSI) with aminopyrazolo[3,4- d ]pyrimidines 2 was found to produce triazolopyrimidinones 5 . The MTT test that quantifies mitochondrial reductive function demonstrated that in both cell lines tested (PE/CA-PJ41 and HePG2 cells), the benzamide compounds 4 are moderately toxic with PE/CA-PJ41 cells and more sensitive than HePG2 cells.

This study fast synthesizes numerous functionalized pyridoxines using click chemistry and assayed in vitro as inhibitors of the acetylcholinesterase (AChE), butyrylcholinesterase, and two monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the obtained compounds demonstrate good AChE and selective MAO-B inhibitory activities in the micromolar range, especially one compound, called 4k5 , exhibits excellent inhibitory performance against AChE (IC 50 = 0.0816 ± 0.075 μM) and MAO-B (IC 50 = 0.039 ± 0.003 μM). Finally, a docking study is carried out, demonstrating potential binding orientations and interactions of the compounds in terms of the AChE and MAO-B active sites.

Abstrtact A series of 2,2-difluoro-2-arylethylamines was synthesized as fluorinated analogs of octopamine and noradrenaline with the expectation of bioisosteric OH/F exchanges. The syntheses of these compounds were performed by a Suzuki–Miyaura cross-coupling reaction of 4-(bromodifluoroacetyl)morpholine with aryl boronic acids to produce the intermediate 2,2-difluoro-2-arylacetamides, followed by transformation of difluoroacetamide to difluoroethylamine.

2-Pyridone is considered as one of the most famous efficient pharmaceutical compounds. Many approaches were discovered to synthesize 2-pyridone. In this present research, chloroacetylation of benzylamine at simple conditions, EtONa/EtCOONa produced N -benzyl-2-chloroacetamide 2 . Compound 2 was allowed to react with different reagents. These reagents are acetylacetone, ethyl cyanoacetate, ethyl acetoacetate, and diethyl malonate, creating 2-pyridone derivatives with a good yield. The structures of the prepared compounds were elucidated by spectral data (IR, 1 HNMR, and 13 CNMR). The synthesized compound was tested for its antimicrobial activity against the Gram-positive ( Staphylococcus aureus ) and the Gram-negative ( Escherichia coli ) bacteria. In addition, the antifungal activities of the compounds were tested against two fungi ( Candida albicans and Aspergillus flavus ). Molecular docking studies were applied using the Autodock vina method. Theoretical methods prove all the experimental results by using molecular docking using Autodock vina and by ADEMT studies. The docking results represent that compound 20 had the best docking free energy, and it is the effective compound toward the selected bacterial and fungal proteins. ADME studies showed that the only compound 18 could cross the blood–brain barrier, and compound 15 was predicted to be soluble.

Two independent and consecutive intermolecular Michael addition of 1,3-dimethylbarbituric acid to 2,6-diarylidenecyclohexanone as an α,β-unsaturated ketone leads to synthesis of a new type of meso form 5,5′-((2-oxocyclohexane-1,3-diyl)bis(arylmethylene))bis(1,3-dimethylpyrimidine-2,4,6(1 H ,3 H ,5 H )-trione) in good yield. These compounds showed a 2D-polymeric structure via intermolecular H-bonds. Structure elucidation is carried out by 1 H NMR, 13 C NMR, FT-IR, and X-ray diffraction analyses. A plausible reaction mechanism is discussed. Graphical abstract

A convenient C(sp 3 )–C(sp 3 ) oxidative dehydrogenative coupling reaction of 1,4-benzoxazin-2-ones with malonate esters was developed under mild conditions to obtain the respective ester malonates in high yields. Reactions take place in [omim]FeCl 4 , acting as both the solvent and the catalyst. Under [omim]Cl/FeCl 3 -DDQ conditions, derivatives of 1 coupled with malonate 2 to give the target molecules within 1–2 h time periods. The ionic liquid was recovered and reused in the next reactions without losing its efficiency. Graphical abstract

In this article, for the first time, N,N,N -triethyl-3-iodopropan-1-aminium triiodide [N 2223I ] [I 3 ] was synthesized and utilized as both a reagent and a solvent in combination with H 2 O 2 (35%) to convert aromatic compounds into their corresponding iodo derivatives. The iodination was accomplished in the absence of organic solvents, and in most instances, water was the sole extraction solvent used. The consumed reagent N,N,N -triethyl-3-iodopropan-1-aminium iodide was comfortably recycled. Graphical abstract

Benzothiazole derivatives are essential intermediates in synthesizing a wide variety of medical and pharmaceutical compounds, and there is a great demand for a simple and efficient method to synthesize benzothiazoles under mild reaction conditions. Organic electrosynthesis as an energy-efficient process represents an environmentally benign and safer method than traditional methods for organic synthesis. Herein, we present bromine-free and straightforward synthesis of 2-amino benzothiazole derivatives via the reaction of aniline derivatives and ammonium thiocyanate using electrosynthesis in the presence of sodium bromide both as an electrolyte and as a brominating agent at room temperature in isopropyl alcohol (i-PrOH) as a solvent. The reaction of ammonium thiocyanate via C–H thiolation routes, using various aniline derivatives, resulted in a simple, green, and bromine-free synthesis of 2-amino benzothiazole in moderate to good yields under mild reaction conditions. Riluzole drug can be produced using the same procedure in moderate yields. Graphical abstract

The purpose of this study was to prepare various derivatives of 4-amino-2-(3-fluoro-5-(trifluoromethyl)phenyl)-6-arylpyrimidine-5-carbonitrile ( 6a–6h ) using a three-step procedure. The derivatives were screened in vitro for activity against Mycobacterium tuberculosis strain H37Rv . The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Eight compounds showed activity against Mtb H37Rv, and among them, 6f showed the best value of MIC, IC 50 (53 μM) and IC 90 (62 μM). Minimum bactericidal concentration of compound 6f was higher than its MIC and was more time-dependent than the concentration. Compound 6f was more active against M. tuberculosis H37Rv under low oxygen than metronidazole and did not show good potency in different treatments and non-tuberculous mycobacteria. Furthermore, a molecular docking study against mycobacterial enoyl-ACP reductase (InhA) could provide valuable insights into the plausible mechanism of action, which could set the theme for lead optimization. Graphical abstract

Three complexes, namely complex ( 1 ), complex ( 2 ), and complex ( 3 ), were synthesized and characterized by X-ray diffraction, thermogravimetric study, and elemental study. Complex ( 1 ) comprises discrete binuclear clusters, where two oxygen atoms of 2-chloro-5-nitrobenzoic acid bridge the two copper atoms. Complex ( 2 ) is a six-coordination structure consisting of four nitrogen atoms and two oxygen atoms in 2-chloro-5-nitrobenzoic acid and 1,10-phenanthroline to furnish a twisted octahedron. Complex ( 3 ) is a six-coordination structure consisting of four oxygen atoms and two nitrogen atoms from the 2-chloro-5-nitrobenzoic acid, methanol, and 2,2′-dipyridyl to furnish a distorted octahedral geometry. Metal complexes’ anti-tumor activity was also investigated by the MTT assay. Of the complexes tested, complex ( 1 ) could induce apoptosis in these A549 lung cancer and Caco-2 colon adenocarcinoma cells and complex ( 2 ) could induce apoptosis in Caco-2 colon adenocarcinoma cells. CCDC for complex ( 1 ) was 1543354, CCDC for complex ( 2 ) was 1546991, and CCDC for complex ( 3 ) was 1543417.

Indomethacin is a nonselective nonsteroidal anti-inflammatory drug with serious side effects such as depression, hallucination, and gastrointestinal irritation. This study aims to enhance indomethacin lipid solubility of indomethacin derivative to use it for the topical formulation since topical formulation may lower the unwanted side effects. The lipid solubility was achieved by adding various alkyl groups (methyl, ethyl, propyl, and isopropyl) to the drug via an ester linkage. The measured log p of these compounds was higher compared to the underivatized indomethacin. Furthermore, an ointment of each ester was formulated and was tested on mice skin using Franz diffusion. The best absorption was observed for methyl indomethacin with threefold increase in permeability compared to indomethacin. This study approves using derivatized indomethacin as a topical formulation with improved efficacy compared to the present gel formulation in the market.

An innovative heterocyclic biologically active chalcone 1,2,3-triazole analogs (6a–j) were prepared to extract excellent yields by coupling the substituted aryl azides (5a–5j) and 5-ethynyl-1,2,3-trimethoxybenzene, by using the method of Huisgen azide–alkyne cycloaddition. The typically synthesized analogs were elucidated by IR, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR, and Electron spray ionization (ESI)-mass spectroscopy and tested for their cytotoxicity effectiveness in MTT assays against the A549 lung cancer cells. The cytotoxic studies suggested that a few analogs showed moderate to good activities. The compounds 6i and 6c showed low cytotoxicity against the A549 cell line among 12 analogs, the values of IC 50 were displayed in the range of 65.05 ± 1.12 and 71.56 ± 1.29 µM, respectively. The compound 6j showed slightly less cytotoxicity but showed good selectivity against A549 cell lines.

A series of benzo (dibenzo)dioxadiaza and triazamacrocyclic ether compounds carrying 1,2,4-oxadiazole group has been successfully synthesized through N -substitution with 3- p -phenylsubstituted-5-chloromethyl-1,2,4-oxadiazoles. The structures of all the novel macrocycles were confirmed by spectral/physical data including HRMS measurements. Graphical abstract

Three novel rhodium complexes, with l -tyrosine ( l -Tyr), l -arginine ( l -Arg), or 2,4-diamino-6-phenyl-1,3,5-triazine (Dpt) as a ligand, named as [Rh(cod)( l -Tyr)], [Rh(cod)( l -Arg)], and [Rh(cod)(Dpt) 2 ], respectively, had been synthesized for catalyzing the polymerization of phenylacetylene. Their yields were 62.34, 54.87, and 58.21%, respectively, by the most suitable synthesis conditions at 25°C for 4 h. The structures and purity of these complexes were proved by 1 H NMR, element analysis, and scanning electron microscope (SEM). It has been examined that phenylacetylene could be polymerized by the three complexes as catalysts with high degrees of polymerization ( n = 368, 385, and 664, respectively) and yields (about 87.62, 88.39, and 59.67%, respectively). In conclusion, compared with traditional [Rh–N] type catalysts, the novel [N–Rh–N] type catalyst ([Rh(cod)(Dpt) 2 ]) gained better catalytic performance. By comparing the yield, Mw, and degree of their polymerization, the polymerization mechanism was found under the [N–Rh–N] type rhodium catalyst system.

A simple and effective method for synthesis of indeno-benzofurans derivatives using polyphenols and ninhydrins is explored using an acidic catalyst based on DABCO (1,4-diaza bicycle [2.2.2] octane)-based ionic liquid. The products of these types of reactions have very low yields without catalysts, but with DABCO-AIL, the yields are excellent, reaction times are reduced, and the media are cleaner. Using infrared (IR), proton nuclear magnetic resonance ( 1 H NMR), Carbon-13 nuclear magnetic resonance ( 13 C NMR), and mass spectrometry, the structures of products can be confirmed. There is evidence that oxidative stress plays a role in the pathophysiology of numerous diseases, including diabetes. Therapeutic antioxidants are promising candidates for the prevention and treatment of such diseases. To investigate the antioxidant properties of all synthesized derivatives, the 2,2-diphenyl-1-picrylhydrazylhydrazyl-hydrate (DPPH) assay was used. Derivatives 3d and 4 with the highest antioxidant effect (with IC 50 value of 0.015 µmol/mL) were selected to evaluate the anti-diabetic effect using the Bernfeld method. The best result was seen at 0.8 mg/mL of 4 derivative and results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test revealed that 4 at this concentration lacked cellular toxicity, too.

Based on 2-(2,6-dioxopiperidin-3-yl)-4-fluoroisoindoline-1,3-dione as a raw material, a series of novel pomalidomide linked with diphenylcarbamide derivatives were synthesized through several step reactions of substitution, click reaction, and addition reaction. The structures of these compounds were confirmed by 1 H NMR, 13 C NMR, and MS. We discovered that some of the compounds are capable of suppressing indoleamine pyrrole-2,3-dioxygenase-1 activities in in vitro experiments, in which the inhibitory activity of 5b reached the level of benefits. Graphical abstract

Many coumarin derivatives have good biological activity and application value in fluorescent probes. Therefore, synthetic routes to coumarin derivatives have also attracted the attention of many research groups. In this work, based on the Pechmann coumarin synthesis method, the influence of various Lewis acids on the reaction was discussed, and the optimal synthesis conditions of 7-hydroxy-4-substituted coumarins were explored. Based on the experimental results, a possible mechanism was proposed, which provides a reference for future industrialized production of coumarins.

Carpesium (Family – Compositae) is a genus with 24 species of mainly perennial herbs. Several species of this genus have served as folk medicine in China and Korea for their antipyretic, anti-inflammatory, analgesic, antifungal, antibacterial, and cytotoxic activity properties. Chemical constituents are mostly sesquiterpenes, diterpenes, glycosides, and several other types of compounds. This article summarizes the literature on the isolated and identified constituents from various Carpesium species and their various biological activities.

Analogs of a new heterocyclic system were obtained from the reactions of 3-amino-1,2,4-triazine with coupling reagents such as boronic acids, and terminal alkynes in the presence of a palladium catalyst. Other reactions such as amination of the triazine at position 5, followed by electrophilic reactions with phenyl isocyanates and benzoyl chlorides, were performed to form new monoureido and benzoylated compounds.