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In this study, we introduce a novel porous metal–organic framework named Co2(bbda)2(DMF)2·5H2O, or MOF‐UoR‐1, synthesized via hydrothermal techniques employing a unique Schiff base ligand. The framework underwent comprehensive characterization, confirming its microporous nature through gas‐sorption measurements. MOF‐UoR‐1 demonstrated remarkable efficacy as a catalyst for the one‐step synthesis of pyrimidine analogs. Structural validation of the synthesized pyrimidines was accomplished via 1H‐nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) analyses. Through systematic experimentation, the optimal catalyst dosage (40 mg) was determined, showcasing its effectiveness across various aldehydes, 1,3‐carbonyl compounds, and urea substrates. Noteworthy is the broad applicability of this environmentally friendly protocol, which offers advantages such as high yields (96%), rapid reaction times (90 min), straightforward product isolation, and product purity without necessitating column chromatography. Furthermore, the catalytic integrity of the framework remained intact, enabling its reuse without compromising performance. This research presents a promising approach for the synthesis of pyrimidine derivatives, with significant implications for sustainable and efficient chemical synthesis methodologies. [ABSTRACT FROM AUTHOR]

Two series of C‐Mannich base derivatives were synthesized and evaluated through the reaction of formaldehyde, two thiazolo‐pyrimidine compounds, and various 2°‐amines. The chemical structures and inherent properties of the synthesized compounds were authenticated using a variety of spectroscopic techniques. The aseptic bactericidal potential of the compounds was assessed alongside five common bacterial microbes, with Ampicillin employed as the reference drug. Compounds 9b and 9d demonstrated comparable antibacterial activity to ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL. Furthermore, compounds 9f and 10f exhibited noteworthy action against Staphylococcus aureus (MIC: 250 μg/mL). Compounds 10b and 10f displayed excellent efficacy versus Escherichia coli, boasting (MIC: 50 μg/mL). Molecular docking studies elucidated the necessary connections and energies of molecular entities with the E. coli DNA gyrase B enzyme, a pivotal target in bacterial DNA replication. Further thermodynamic stability of the ligand‐receptor complex of 10b and 10f were further validated though 200 ns molecular dynamics simulation. The findings highlight the potential of these synthesized derivatives as effective antibacterial agents and provide valuable insights into their mechanism of action. Highlights: Two series of C‐Mannich base derivatives were synthesized by reacting formaldehyde, two thiazolo[3,2‐a] pyrimidine compounds, and seven heterocyclic amines.The antibacterial potential of the compounds was evaluated against five common bacterial pathogens, with Ampicillin as the reference drug.Compounds 9b and 9d showed comparable antibacterial activity to Ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL.Compounds 9 f and 10 f exhibited notable activity against Staphylococcus aureus, with MIC values of 250 μg/mL.Compounds 10b and 10 f displayed excellent efficacy against Escherichia coli, with MIC values of 50 μg/mL.Molecular docking studies revealed the binding interactions and energies of the compounds with the E. coli DNA gyrase B enzyme, a crucial target in bacterial DNA replication.The binding stability of promising compounds 10b and 10 f was further validated through 200 ns molecular dynamics (MD) simulations. [ABSTRACT FROM AUTHOR]

Chemotherapy drugs often cause various adverse reactions and affect normal tissues, so it is of great significance to design effective targeted anti‐tumor drug delivery methods. We constructed a series of self‐assembled supramolecular modular structures and explored whether they could become an effective targeted antitumor fluorescent agent. UV and fluorescence spectra show that it has fluorescence. The drug release curve was determined by dialysis method and the results showed that the release rate of PCB series composites was the highest under pH = 5. The curcumin pyrimidine derivative was embedded in the structure, and the formation of the complex was confirmed by infrared spectroscopy. The results for the cell imaging indicated that with the decrease of environmental pH value, the ability of PCB‐1 and PCB‐2 to penetrate the biofilm barrier into cells increased, suggesting that they have targeting action. The results of the cell viability test showed that PCB‐1 and PCB‐2 had a good inhibitory effect on MGC and HeLa cells. TEM showed that PCB‐1 was a regular hexahedron structure and PCB‐2 was a rod structure. In addition, the encapsulation efficiency of PCB‐1 and PCB‐2 was tested to be 86.50% and 88.57%, respectively, with drug loading rates of 27.62% and 28.38%, and Zeta potential values of +35 and +32. In conclusion, PCB‐1 and PCB‐2 are good potential anti‐tumor fluorescent agents. [ABSTRACT FROM AUTHOR]

2‐Amino pyrimidines are vital molecules that exhibit diverse biological activities and serve as structural motifs in various pharmaceutical drugs. Four new series of triazole‐linked glycohybrids of 2‐amino‐pyrimidinones were designed and efficiently synthesized, using a microwave‐assisted method under click chemistry reaction conditions. The N‐propargyl‐2‐aminopyrimidinone and O‐propargyl‐2‐aminopyrimidine derivatives successfully underwent the click reactions with 1‐azido‐tetra‐O‐acetyl‐β‐D‐glucose, D‐galactose and D‐mannose. In this work, we reported the series of novel thirty‐three new triazole‐linked glycohybrid molecules with stereochemical diversity and diverse substitution patterns. [ABSTRACT FROM AUTHOR]

Four novel Pd (II), Cu (II), VO (II), and Ag(I) complexes were prepared from benzimidazole ligand through bidentate chelating mode. Alternative spectral and analytical tools were applied to elucidate their structural and molecular formulae. This study was extended to investigate stability and stoichiometry of complexes in solution, using standard methods. In addition, the best atomic distribution within structural forms was obtained via the density functional theory (DFT) method. This computational study fed us with significant physical characteristics for differentiation. Also, DFT/time‐dependent DFT computations were performed applying (B3LYP/6‐311++G[d,p]/aug‐cc‐pVTZ/aug‐cc‐pVTZ‐PP) level in order to investigate the electronic behavior of the compounds. These results demonstrated good agreement with the experimental data. Computational data discriminate Pd (II) complex by some physical features, which may be promising in the catalytic field. This complex was selected to play a catalytic function to synthesize 3‐methyl‐4‐phenyl‐4,9‐dihydro‐1H‐pyrazolo[3,4‐d][1,2,4]triazolo[1,5‐a]pyrimidine derivatives using microwave irradiation in a one‐pot reaction. The catalyst was selected for this application based on the history of Pd (II) complexes and the properties expected theoretically. A condensation reaction for 3‐methyl‐5‐pyrazolone, aromatic aldehyde, and 5‐aminotetrazole was carried out under mild reaction conditions by microwave irradiation. All reaction conditions were optimized among those variable Lewis acid catalysts in comparison with our new complexes. DOBPAPd catalyst displayed superiority in overall trials with high yield, short time, and green conditions (solvent H2O/EtOH). Also, the recovery of hetero catalyst was succeeded and reused by the same efficiency up to five times after that the efficiency was reduced. The mechanism of action was proposed based on the ability of Pd (II) for adding extra‐bonds over z‐axis and supported by theoretical aspects. [ABSTRACT FROM AUTHOR]

2,4,6‐Triamino‐N‐phenylpyrimidine‐5‐carbothioamide (LPH) was synthesized and extensively characterized. Single crystal X‐ray confirms a monoclinic P21/c space group for LPH. The novel ligand and its chelates of Cr3+, Ni2+, and Ru3+ were studied by elemental analyses, spectral (13C‐,1H‐NMR, UV–visible, IR), magnetic, and thermal measurements. IR spectra indicated that LPH behaves in a bidentate mode through the two NH2 groups of the pyrimidine ring and/or a tetradentate coordination involving the nitrogen atoms of the two NH2 of the pyrimidine ring, NH, and the thioketo (C=S) groups, respectively. By utilizing the Gaussian 09 W program in DFT/B3LYP, we are able to conduct computational estimates of LPH and its metal chelates, yielding insightful data regarding their electronic structure and stability. Biological studies were conducted to assess the isolated compounds' activities against anticancer (MCF‐7), antioxidant (DPPH and ABTS), DNA, and antimicrobial proteins. Molecular docking was employed to investigate the chelates' inhibitory properties, specifically their binding propensity with MCF‐7 cells, revealing possible anticancer action. All the data help to understand LPH and its complexes' production, biological characteristics, and possible therapeutic uses. [ABSTRACT FROM AUTHOR]

Indoles and their derivatives have long been studied for their anticancer properties. Breast cancer has been treated using indole‐3‐carbinol, Indirubins, and many other naturally occurring indoles as well as their synthesized equivalents. It has been determined that the AKT pathway is a prospective target for therapeutic strategies in the treatment of breast cancer. The dysregulation of AKT pathway frequently promotes cell proliferation, survival, and resistance to apoptosis. We synthesized a novel group of bisindole clubbed pyridine and pyrimidine derivatives 5(a–l) using water as the solvent and thiamine hydrochloride as the catalyst. Compounds 5 a, 5 c, 5 d, 5 e, and 5 f are the most active against MCF‐7 cells, with an IC50 values of 2.48±0.39, 1.35±0.13, 3.36±0.53, 4.05±0.61 and 1.91±0.28 μM, respectively. Further, in silico docking of the active compound 5 c had the highest binding energy of −10.59 kcal/mol. Additionally, molecular dynanamics simulations were performed for better understanding the mode of interaction of ligand and protein. In conclusion, we have synthesized bisindoles using thiamine hydrochloride as a catalyst that target AKT pathway in breast cancer cells. [ABSTRACT FROM AUTHOR]

Chromenes are an essential class of oxygen‐containing heterocyclic compounds with intriguing biological activity. It is an important moiety for the discovery of new drug candidates. Chromenes are naturally abundant as alkaloids, tocopherols, flavones, and anthocyanins. The incorporation of 4H‐chromene, along with various bioactive heterocycles such as indole, pyrazole, kojic acid, pyran‐2‐one, quinoline, pyridine, pyrimidine, coumarin, sesamol, furan, uracil, benzoimidazole, benzotriazole, thiazole, isoxazole and barbituric acid moieties, into a molecular scaffold has the potential to combine the properties of both components. The synergistic effect of combining different heterocyclic moieties within a 4H‐chromene nucleus results in the formation of valuable compounds with significant biological importance. This review summarizes the different synthetic techniques used for preparing 4H‐chromene‐embedded heterocycles. The common mechanisms of key reactions and the significance of the method are discussed. [ABSTRACT FROM AUTHOR]

Pyrimidine and its derivatives play a paramount role in drug discovery as privileged pharmacophores with considerable chemical and biological significance and its presence in genes. This review aims to assemble a systematic evaluation of synthetic tactics of various fused pyrimidine derivatives containing nitrogen heterocycles such as pyridopyridines, pyridopyrimidines, and pyrimidopyrimidine from a pharmacological point of view and deliver an overview of methodologies presenting the chemistry of fused pyrimidine derivatives. The review details the importance of various catalysts and ring substitution using various electrophilic and nucleophilic reagents. These synthetic strategies were elaborated based on the different synthetic routes that lead to the specific type of pyrimidine and pyridine fused derivatives. The literature accumulates various developments in one‐pot condensation, the Knoevenagel–Michael addition mechanism, microwave and ultrasound irradiation, intramolecular cyclization, nano‐catalytic reactions, and so forth. Short reaction times, catalyst reusability, solvent‐free conditions, excellent yields, and stereo‐selectivity are some of the benefits of certain synthetic approaches. [ABSTRACT FROM AUTHOR]

The present study mainly focused on synthesizing novel triazolo[1,5‐a]pyrimidine‐6‐carboxamide derivatives using multicomponent reaction. Synthesized derivatives were duly characterized using spectroscopic methods of analysis FT‐IR and mass spectroscopy, and 1H NMR and 13C NMR confirmed the structure of compounds. Further, the potential of the synthesized compounds against Plasmodium falciparum dihydrofolate reductase (Pf‐DHFR) inhibitors was evaluated by in vitro antimalarial activity, and the results of the study showed moderate to good antimalarial profile of synthesized entities. In silico study of all the synthesized compounds was carried out using Schrödinger LLC‐2020‐3 Software to explain the binding mode and interactions between molecules and pf DHFR enzyme. To study the drug likeliness of molecules, 3D QSAR and Pharmacokinetic studies have been carried out, and the results obtained showed a good pharmacokinetics profile of two compounds, namely AMP‐24 and AMP‐28, having good IC50 values concerning standard drugs. Further, the in vitro enzyme inhibition assay results suggested that the synthesized compound interacts nicely with the enzyme and might be used as a potent antimalarial agent. [ABSTRACT FROM AUTHOR]

The histone deacetylases (HDACs) are being explored as a promising therapeutic target for the treatment of various diseases. Here, the synthesis of a series of pyrimidine‐based 1,3,4‐oxadiazoles, in which the oxadiazole scaffold is attached to the pyrimidine ring via a methyleneoxy spacer, is described and their HDAC inhibitory activity studied. The target compounds were synthesized by sequence of reactions involving O‐alkylation of 2‐(methylthio)pyrimidin‐4(3H)‐ones with ethyl 2‐bromoethanoate followed by oxidation of the 2‐methylthio group, displacement of the obtained 2‐methylsulfonyl group with amines, hydrazinolysis of the obtained ethyl (2‐amino‐substituted pyrimidin‐4‐yloxy)acetates to give the corresponding hydrazides and their cyclization under the treatment with ethyl O‐ethyl xanthate or carbonyldiimidazole to 1,3,4‐oxadiazole‐2(3H)‐thiones and 1,3,4‐oxadiazol‐2(3H)‐one, correspondingly. In addition, two 1,3,4‐oxadiazole‐2(3H)‐thiones were converted into (N3)‐morpholinomethyl derivatives by the Mannich reaction with formaldehyde and morpholine. The yields of intermediates and target compounds ranged from moderate to excellent. The synthesized compounds were characterized by 1H and 13C NMR spectra and HRMS data, their purity was controlled by TLC. The synthesized pyrimidine‐based 1,3,4‐oxadiazoles (18 compounds) were tested as inhibitors of the HDAC4 and HDAC8 isoforms and their inhibitory activity was compared with that of Vorinostat. Most of the oxadiazolethiones containing methyl group at the position 6 of the pyrimidine moiety were found to be more selective towards HDAC8, while oxadiazolethiones with propyl group in the pyrimidine ring were active against HDAC4. Among the tested compounds, 5‐((2‐(dibutylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (48) was found to have the strongest inhibitory activity for HDAC4 isoform (IC50 = 4.2 μM vs. IC50 = 59 μM for Vorinostat) while 5‐((2‐(cyclopentylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (50) was the most potent HDAC8 inhibitor (IC50 = 6.8 μM). [ABSTRACT FROM AUTHOR]

An efficient chromoselective photochemical process is presented for the synthesis of 2H‐azirines and 1,3‐diazabicylo[3.1.0]hex‐3‐enes from readily available vinyl azides. The method exploits continuous flow photochemistry to enable the safe consumption of the hazardous azide group and provides uniform irradiation using high‐power LEDs at 365–450 nm. Additionally, a scaled telescoped process has been developed providing access to drug‐like 1,6‐dihydropyrimidines and pyrimidines via integrated ring‐expansion and oxidation reactions. Given the prevalence of various azacyclic targets in pharmaceutical, agrochemical and materials applications it is anticipated that this methodology will enable further exploitations of these important scaffolds. [ABSTRACT FROM AUTHOR]

Pyrimidine‐based derivatives have attracted a lot of interest in heterocyclic chemistry due to its versatile structure and diverse biological activities. This study provides a comprehensive overview of synthetic strategy of different pyrimidine ring and highlights their biological importance. In this article, we start off by going through the fundamental procedures for the synthesis of pyrimidine scaffolds, including both conventional and contemporary synthetic techniques. These works cover a range of therapeutic domains, such as effects that are anticancer, antibacterial, antiviral, anti‐inflammatory, antioxidant, antimalarial, and so on. Moreover, we have summarized with a discussion of future prospects and challenges in the field of pyrimidine heterocyclic chemistry. This thorough review is a significant resource for researchers in medicinal chemistry and related fields since it offers insightful information about the synthetic methods and biological applications of pyrimidine‐based derivatives. [ABSTRACT FROM AUTHOR]

1,3,4‐Oxadiazole and its derivatives are well known assorted motif in drug design and development. The development of bacterial infection drug resistance serves as justification for the discovery of novel antimicrobial drugs. Thus, a novel series of 1,3,4‐oxadiazole derivatives linked to pyrrolo[2,3‐d]pyrimidine 6 a–f and 7 a–e was designed, synthesized and fully characterized by 1H‐NMR, 13C‐NMR, FT‐IR and mass spectroscopic analysis. All of the compounds′ in‐vitro antibacterial and antifungal activities were reported, and final oxadiazoles 6 d, 6 e, 6 f, and 7 e showed excellent antimicrobial inhibitory activity as compared to standard drugs. The compounds 6 f and 7 a exhibited potent antifungal activity as a potent inhibitor against C. albicans with MICs 4.0±0.03, 7.5±0.02 μg/mL respectively. In order to determine the different binding interactions that the most active oxadiazoles had with the Staphylococcus aureus DHFR enzyme, a docking study was conducted. The results indicated that the residues of amino acid Thr96(X), Leu62(X), Arg44(X), Asn18(X), Glu17(X), Lys45(X), Thr121(X), Gln95(X), Asp120(X), Ser64(X), Gly94(X), and Phe16(X) had promising energy value, within the range of −6.84 to −9.63 kcal/mol (PDB: 3FRA). The most effective inhibitors, 6 and 7, also underwent in silico ADMET tests to predict their pharmacokinetic and physicochemical characteristics. [ABSTRACT FROM AUTHOR]

Over the years, human dihydroorotate dehydrogenase (hDHODH), which is a key player in the de novo pyrimidine‐biosynthesis pathway, has been targeted in the treatment of several conditions, including autoimmune disorders and acute myelogenous leukaemia, as well as in host‐targeted antiviral therapy. A molecular exploration of its inhibitor‐binding behaviours yielded promising candidates for innovative drug design. A detailed description of the enzymatic pharmacophore drove the decoration of well‐established inhibitory scaffolds, thus gaining further in vitro and in vivo efficacy. In the present work, using X‐ray crystallography, an atypical rearrangement was identified in the binding pose of a potent inhibitor characterized by a polar pyridine‐based moiety (compound 18). The crystal structure shows that upon binding compound 18 the dynamics of a protein loop involved in a gating mechanism at the cofactor‐binding site is modulated by the presence of three water molecules, thus fine‐tuning the polarity/hydrophobicity of the binding pocket. These solvent molecules are engaged in the formation of a hydrogen‐bond mesh in which one of them establishes a direct contact with the pyridine moiety of compound 18, thus paving the way for a reappraisal of the inhibition of hDHODH. Using an integrated approach, the thermodynamics of such a modulation is described by means of isothermal titration calorimetry coupled with molecular modelling. These structural insights will guide future drug design to obtain a finer Kd/logD7.4 balance and identify membrane‐permeable molecules with a drug‐like profile in terms of water solubility. [ABSTRACT FROM AUTHOR]

Dienamine 2 was synthesized by reacting 5‐aminopyrazole 1 with two moles of (DMF DMA). Enamine 2 underwent subsequent reactions with various reagents in different reaction media, leading to the formation of distinct compounds. In an acidic environment, enamine 2 reacted with acetyl acetone, benzoyl acetone, dimedone, and ethyl acetoacetate, resulting in the synthesis of compounds 9a, 9b, 13, and 17, respectively. Conversely, in a basic medium, dienamine 2 combined with malononitrile, ethyl cyanoacetate, and malononitrile dimer, yielding compounds 21a, 21b, and 25. Moreover, by reacting with ammonium acetate in acetic acid, dienamine 2 produced compounds 28. The synthesized compounds underwent in vitro testing against various bacterial and fungal strains, revealing significant antibacterial activity against hazardous bacterial strains. To identify potential bacterial targets, an in‐silico study was initiated. Molecular docking investigations indicated that compound 25 exhibited the highest binding affinity toward dihydrofolate reductase and penicillin‐binding proteins. Furthermore, compound 25 demonstrated robust physiochemical properties, bioavailability, and drug‐like characteristics. These results collectively suggest the potential of compound 25 as a promising antibacterial agent with favorable drug properties. [ABSTRACT FROM AUTHOR]

A concise set of 4‐substituted pyrazolo[3,4‐d]pyrimidine carboriboside analogues was synthesized in a divergent fashion via a central intermediate. An oxaziridine reagent allowed the synthesis of a crucial hydrazine glycon intermediate, which was transformed through a base‐build‐up strategy into the desired intermediate using a commercially available pyrimidine building block. Reaction with a variety of nucleophiles allowed late‐stage diversification. All analogues were evaluated for activity against a representative panel of Trypanosomatida. A methoxy‐substituted analogue displayed single‐digit micromolar activity against two subspecies of Trypanosoma brucei in cellular assays. [ABSTRACT FROM AUTHOR]

This work aimed to create and characterize some new bioactive chelates of bis azodye ligand, 5‐((2‐hydroxy‐4,6‐dioxo‐1,4,5,6‐tetrahydropyrimidin‐5‐yl)diazenyl)naphthalen‐1‐yl)diazenyl) pyrimidine 2,4,6 (1H,3H,5H)‐trione. Except for the Sm(III) chelate, which exhibited a (3M:1L) molar ratio, all chelates had a (2M:1L) stoichiometry. According to Fourier transform infrared spectroscopy (FT‐IR), azo groups were not included in chelating with all ions except Sm(III), where just one azo group was coordinated. With the Ni(II) and Zn(II) ions, the ligand behaved as OON‐tridentate moiety; with the Co(II) and Cu(II) ions, it behaved as ON‐bidentate moiety. Co(II) and Cu(II) chelates had square planar structure, and Ni(II) and Zn(II) chelates had square pyramidal geometry. The chelates had greater thermal stability than the uncoordinated ligand due to the chelate's structure. [Sm3(H4L)(OH)7(NO3)2.H2O].4.5EtOH exhibited the maximum thermal stability, which may be due to the large number of solvent molecules and the high number of chelate rings. With the exception of the Sm(III) chelate, all of the examined chelates were more cytotoxic against MCF‐7 and Hep‐G2 cells than their parent ligand. With the exception of the Zn(II) chelate, which demonstrated activity on Hep‐G2 rather than MCF‐7, the effects of each metal chelate on the two cells were nearly equivalent. All of the studied chelates, especially Zn(II) and Co(II), were potent as antioxidants more than the native ligand. To support experimental findings, density functional theory (DFT) studies were performed via the CAM‐B3LYP/LanL2DZ method, and the geometry of the ligand and its chelates had been validated. [ABSTRACT FROM AUTHOR]

This current investigation represents the new series of fused thieno-pyrimidine with synthesized tetrazole analogs (6a–j). Intermediates thieno-[2,3-d]- pyrimidine were prepared by utilizing the Gewald method, and tetrazole (5a–j) was synthesized by [3 + 2] cycloaddition of azide and appropriate nitrile. All the prepared novel molecules were characterized and confirmed by ¹HNMR, 13CNMR, LC-MS, and FT-IR spectral analysis. [ABSTRACT FROM AUTHOR]

Oxazolo[5,4‐d]pyrimidine derivatives have been reported to exhibit interesting biological activities. Herein, we described a solid‐phase synthetic method to produce N‐alkyl‐7‐alkylamino‐2‐aryloxazolo[5,4‐d]pyrimidine‐5‐carboxamide derivatives. The strategy consists of loading the template compounds (i.e., 2‐aryl‐6,7‐dihydrooxazolo[5,4‐d]pyrimidin‐7‐one‐5‐carboxylic acids) onto aminated acid‐sensitive methoxybenzaldehyde (AMEBA) resins, the subsequent benzotriazol‐1‐yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP)‐mediated direct amination with primary/secondary amines, and the final cleavage from the solid support to afford the target compounds. The template 2‐aryl‐6,7‐dihydrooxazolo[5,4‐d]pyrimidin‐7‐one‐5‐carboxylic acids were prepared using a five‐step solution‐phase synthetic route from ethyl 2‐cyano‐2‐(hydroxyimino)acetate. BOP‐mediated direct amination conditions were optimized by a solution‐phase model study. The solid‐phase synthetic method provided the 17 target compounds in 16%–92% five‐step overall isolated yields from the Merrified resin for selected template compounds and primary/secondary amines. [ABSTRACT FROM AUTHOR]

The reactions of cage‐opened C60 derivatives with aromatic diamines are known to cause an orifice‐enlargement in association with incorporating extended π‐systems. The present work focuses on 1,2‐, 2,3‐, and 1,8‐diaminonaphthalenes for the synthesis of a series of naphthalene‐fused fullerene derivatives. For the former two, orifice enlargement proceeded by cleaving two C=C bonds to afford an opening with a ring‐atom count of 20, in which the naphthalene moiety was fused by a pyrazine ring. For the reaction with 1,8‐diaminonaphthalene, only one C=C bond was cleaved to give a 17‐membered‐ring opening where the diaminonaphthalene moiety was fused by a pyrimidine ring. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second most common cause of cancer‐related deaths and the third most common cancer worldwide. Because of its importance in DNA biosynthesis, thymidylate synthase (TS) has gathered attention as a promising target for cancer therapy. Herein, we have designed and synthesized 12 novel 5‐(N‐Benzyl indol‐3‐yl) pyrido[2, 3‐d] pyrimidine based derivatives and assessed their anticancer activity against HCT 116, MCF‐7, Hep G2, and PC‐3 cell lines. For compounds 5 a and 5 f TS inhibitory activity was also performed along with in silico studies. Further, all the synthesized compounds exhibited anticancer activity, but particularly, compounds 5 a and 5 f were showed excellent anticancer activity having IC50 values of 1.09±0.61, 5.54±0.81, 6.44±0.91, and 5.12±0.65 μM and 1.03±0.96, 3.09±0.52, 4.12±0.59, and 7.06±0.60 μM respectively with control Raltitrexed (IC50 1.02±0.51, 1.88±0.61, 1.30±0.89, and 2.09±0.67 μM respectively) and hTS inhibitory activity with IC50 of 18.91±1.09 and 16.19±0.96 nM with control Raltitrexed (IC50 12.25±1.21 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 5 a and 5 f to the catalytic site of TS. Additionally, ADME characteristics were also in the acceptable range for these compounds. Based on the anticancer activity, SAR was also performed for lead optimization. [ABSTRACT FROM AUTHOR]

In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2‐a]thieno[2,3‐d]pyrimidine derivatives using in a single [3 + 2] reaction cycloaddition reaction of 3‐(3‐iodoprop‐2‐yn‐1‐yl)thieno[2,3‐d]pyrimidin‐4(3H)‐one (4) followed by C‐C bond coupling with various aryl azides in a PEG‐400 medium. All of the newly synthesized compounds were evaluated in vitro for EGFR kinase inhibitory action as well as anti‐breast cancer activity against MDA‐MB‐231 and MCF‐7 breast cancer cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 5g and 5i, demonstrated excellent anticancer activity against both cancer cell lines, with IC50 values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.467 ± 0.063 and 0.412 ± 0.081 μM). The in silico studies of five potent compounds 5f, 5g, 5h, 5i, and 5k were also carried out to identify the interactions against the EGFR receptor and found that the energy calculations were covenant with the obtained IC50 values. [ABSTRACT FROM AUTHOR]

In this work, we report an effective, one‐pot syntheses of benzo[4,5]imidazo[1,2‐a]pyrimidine and pyrano[4,3‐b]pyran derivatives using L‐glutamine functionalized nanoparticles (Fe3O4@SiO2@L‐glutamine NPs) under microwave irradiation. The organo‐nanocatalyst underwent characterization through diverse techniques, including FT‐IR, p‐XRD, SEM, TEM, EDX, XPS, TGA, and VSM. Microwave irradiation and multicomponent reactions synergistically yield excellent product yields (≈80%–95%) in shorter reaction times (≈6–15 min) with a broader substrate scope. The organo‐nanocatalyst displays notable catalytic efficacy, evidenced by high turnover numbers (TON) and turnover frequencies (TOF) across syntheses. This innovative protocol showcases exceptional efficiency, cost‐effectiveness, and environmental friendliness, with advantages like minimal reaction conditions, easy catalytic recovery, recyclability, operational simplicity, and the use of eco‐friendly solvents. [ABSTRACT FROM AUTHOR]

A novel organic salt containing DOPO and pyrimidine (AD) was successfully synthesized through a simple acid--base neutralization reaction. The salt was used as a reactive flame retardant for epoxy resin. Non-isothermal DSC tests disclosed that the epoxy resin displayed a lower temperature of onset curing and exothermic peak in the presence of AD. By using only 3 wt% AD, the epoxy resin achieved a UL-94 V-0 rating and a limited oxygen index value of 27.4%, revealing the high flame-retardant efficiency of AD. AD inhibited the release of heat and smoke. The analysis of the flameretardant mode of action indicated that AD was able to impede combustion not only by the dilution and quenching effects in the gas phase but also by the charring effect in the condensed phase. During UL-94 testing, 3 wt% AD gave the epoxy resin good flame retardancy due to the charring and blowing-out effects formed by adding AD. The blowing-out effect was that the release of strong airflows suppressed or even blew out the flame based on the dilution and quenching effects of phosphorous-containing radicals and numerous non-combustible gases produced by the degradation of AD and epoxy resin matrix. Additionally, the incorporation of AD slightly increased the glass transition temperature and the tensile and flexural strengths of the epoxy resin. This study provided a meaningful attempt to improve the flame retardance of epoxy resin by introducing a reactive pyrimidine-organophosphonic acid salt. [ABSTRACT FROM AUTHOR]

To address the increasing levels of carbon dioxide (CO2) in the atmosphere, various heterocyclic N/B‐based intramolecular frustrated Lewis pairs (IFLPs) have been experimentally and theoretically investigated. Reports have shown them to be a potential catalyst for CO2 sequestration, however, a comparative rationale of these IFLPs has not been reported. Thus, in the present work, we have proposed an uninvestigated IFLP based on i. e., 2‐boranyl‐1,3,5‐triazine (BT) and compared with previously reported borylated imidazole (Im) and pyrimidine (Prm) for CO2 abduction. The density functional theory (DFT) base calculations have been carried out to probe the reaction mechanism and thorough natural bond orbital analysis has been carried out to get deeper insights into the catalytic behavior of the proposed IFLPs. Further, the effect of substituting the hydrogens at the ring and the B atom of the considered IFLP, by −CH3, −Cl and −OH, on the catalytic behavior has been studied. The results show that the borylated triazines can be a potential catalyst for CO2 sequestration. Also, the catalytic behavior of the presented IFLPs can be modulated by appropriated substitutions. [ABSTRACT FROM AUTHOR]

In the current study, N1‐N4‐bis (3‐(trimethoxysilyl) propyl) butane‐1,4‐diammonium trinitromethanide on titanium dioxide {TiO2−Bis [TMS−NH2+ C(NO2)3−]} was synthesized and characterized using a variety of techniques including energy dispersive X‐ray analysis (EDX), fourier transform infrared spectroscopy (FT‐IR), thermo gravimetric analysis (TGA), field emission scanning electron microscopy (FESEM), and X‐ray diffraction (XRD). Then TiO2−Bis [TMS−NH2+ C(NO2)3−] was used as an efficient nano‐catalyst in the one‐pot synthesis of 1,2,4‐triazolo[4,3‐a] pyrimidine derivatives at 120 °C under the solvent‐free conditions with good to excellent yields. Easy separation of the products from the catalyst, short period of the reaction times, and reusability of the catalyst are among the most important features of the reported method. [ABSTRACT FROM AUTHOR]

Due to their extensive applications in pharmaceuticals and natural substances, organic synthesis and heterocyclic compounds have been at the forefront of research for many years. Pyrimidine is one of the heterocyclic compounds that have various derivatives with promising biological and pharmacological properties. This review article covers the synthesis and biological effects of pyrimidine derivatives, such as pyrano[2,3‐d]pyrimidines, pyrido[2,3‐d]pyrimidines, and furo[2,3‐d]pyrimidines. The compounds discussed in this review have a wide range of biological activities. Recent advances in green chemistry have led to the development of eco‐friendly synthetic methods for producing these bioactive heterocycles. This review aims to present various synthetic methods and biological effects of these compounds and provide new opportunities for organic chemists to develop potent nitrogen‐ and oxygen‐containing heterocycles for future applications. The review highlights examples of successful syntheses and applications of pyrimidine derivatives in the fields of antibacterial, antifungal, anticancer, enzyme inhibition, and antiviral research. [ABSTRACT FROM AUTHOR]

To explore novel natural product‐based nitrogen‐containing heterocyclic compounds with antiproliferative activity, 20 L‐carvone‐derived pyrimidine‐urea compounds 4a–4t were synthesized through the multi‐step reaction of L‐carvone, and structurally characterized by Fourier transform infrared (FT‐IR), hydrogen‐1 nuclear magnetic resonance (1H‐NMR), Carbon‐13 nuclear magnetic resonance (13C‐NMR), and High‐resolution mass spectrometry (HRMS). Besides, the in vitro antiproliferative activity of the target compounds against HepG2, Hela, and MCF‐7 cells was evaluated by methyl thiazolyl tetrazolium (MTT) assay. According to the results, the target compounds showed certain inhibitory activities against the tested cancer cell lines, and five compounds (4b, 4h, 4k, 4l, and 4t) exhibited better inhibition activities against Hela cells than the positive control (5‐FU). Among them, compound 4b held significant antiproliferative activities against Hela and HepG2 cells, and thus deserved further study as a leading compound of new anticancer drugs. In addition, an effective and reasonable three‐dimensional quantitative structure‐activity relationships (3D‐QSAR) model was built by the Comparative molecular field analysis (CoMFA) method to analyze the relationship between the structures of the target compounds and their antiproliferative activities (expressed as pIC50) against Hela cells, and proven to have good predictive ability. Molecular docking was carried out to study the possible binding modes of compound 4b and Survivin, and it was found that compound 4b could be well embedded into the active site, along with the formation of several hydrogen bonds and hydrophobic interactions. [ABSTRACT FROM AUTHOR]

Fibromyalgia patients vary in clinical phenotype and treatment can be challenging. The pathophysiology of fibromyalgia is incompletely understood but appears to involve metabolic changes at rest or in response to stress. We enrolled 54 fibromyalgia patients and 31 healthy controls to this prospective study. Symptoms were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and blood samples were collected for metabolomics analysis at baseline and after an oral glucose tolerance test and a cardiopulmonary exercise test. We identified key symptoms of fibromyalgia and related them to changes in metabolic pathways with supervised and unsupervised machine learning methods. Algorithms trained with the FIQ information assigned the fibromyalgia diagnosis in new data with balanced accuracy of 88% while fatigue alone already provided the diagnosis with 86% accuracy. Supervised analyses reduced the metabolomic information from 77 to 13 key markers. With these metabolites, fibromyalgia could be identified in new cases with 79% accuracy. In addition, 5‐hydroxyindole‐3‐acetic acid and glutamine levels correlated with the severity of fatigue. Patients differed from controls at baseline in tyrosine and purine pathways, and in the pyrimidine pathway after the stress challenges. Several key markers are involved in glutaminergic neurotransmission. This data‐driven analysis highlights fatigue as a key symptom of fibromyalgia. Fibromyalgia is associated with metabolic changes which also reflect the degree of fatigue. Responses to metabolic and physical stresses result in a metabolic pattern that allows discrimination of fibromyalgia patients from controls and narrows the focus on key pathophysiological processes in fibromyalgia as treatment targets. [ABSTRACT FROM AUTHOR]

Fused imidazole and pyrimidine heterocycles represent two important classes of organic compounds. Numerous synthetic methods have been developed for the synthesis of these compounds due to their diverse biological activities and potential pharmaceutical applications. This review provides a comprehensive assessment of the cutting‐edge methods used in the synthesis of fused heterocycles from pyridin‐2‐amines and their aza derivatives involving reaction with 1,3‐dicarbonyl compounds or α‐halo carbonyl compounds. In addition, the Groebke‐Blackburn‐Bienaymé (GBB) reaction, metal‐mediated reactions and other related reaction systems have been considered. We summarize the pertinent literature on related synthetic methods in the period 2020 to 2023. The analysis provided can inform future developments directed at new cost‐effective approaches to the synthesis of fused imidazole and fused pyrimidine analogues. [ABSTRACT FROM AUTHOR]

A new series of hydrazone derivatives incorporating spirocyclic aminopyrimidine with aryl alkanesulfonates were synthesized. The targeted products were obtained in excellent yields via an acid catalyzed reaction of spirocyclic hydrazinopyrimidine with aryl aldehyde sulfonates. The structures of the synthesized hydrazones were studied by the different spectroscopic tools, in addition to the high resolution mass analysis. The antiproliferative activities of the compounds were tested in vitro against the National Cancer Institute (NCI) 60 cell panel by the Developmental Therapeutics Program. Amongst the tested hydrazone compounds, the methansulfonate derivatives showed the highest activities against lung, brain, kidney, and breast cancers. [ABSTRACT FROM AUTHOR]

An efficient one‐pot synthesis of some new series of benzo[5,6]chromeno[2,3‐d]pyrimidine derivatives is reported by the three‐component condensation reaction of 2,3‐dihydroxynaphthalene, 2‐thiobarbituric acid and aromatic aldehydes using sulfuric acid as the catalyst in glacial acetic acid under reflux condition. This transformation apparently proceeds through Michael addition, intra‐molecular heterocyclization and dehydration sequences. This protocol provides cleaner reaction profiles, good to high yields, operational simplicity, easy workup, readily accessible starting materials and not requires column chromatography for isolation of target products in pure form. [ABSTRACT FROM AUTHOR]

The increase in the prevalence of antibiotic‐resistant pathogens leads to a decrease in the number of antimicrobial agents for the treatment of infections and prompts researchers to search for new effective antimicrobial drugs. This study reports the synthesis of novel triphenylphosphonium‐functionalized substituted pyrimidines and in vitro evaluation of their antibacterial and antibiofilm activity. Most of the synthesized derivatives showed high antibacterial activity (MIC = 0.39–1.56 μg/mL) against the methicillin‐resistant strain of S. aureus 222. Compounds 2a and 11 exhibited a high level of antibiofilm activity against S. aureus 222 and E. coli 311. The triphenylphosphonium‐containing pyrimidines 11 and 2a reduced S. aureus 222 biofilm formation by 99.1% and 95.8%, respectively. In addition, compound 2a was the most active against E. coli 311 biofilm formation (the biomass decreased by 98.4%). [ABSTRACT FROM AUTHOR]

A mild Oxone® mediated reaction for direct regioselective C−H selenylation and thiocyanation of pyrazolo[1,5‐a]pyrimidines is established at ambient temperature. This practical and efficient methodology employs Oxone® as a user friendly, green, non‐toxic and cheap reagent to facilitate selenylation and thiocyanation at room temperature. The present method offers high regioselectivity, broad substrate scope, mild conditions and excellent yields. Further, this eco‐friendly approach could easily be extended for mild C−H selenylation and thiocyanation of other heterocycles. Mechanistic studies indicate that the reaction occurs through electrophilic substitution mechanism via generation of an electrophilic chalcogen species. [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) infection causes respiratory disease. Recently, infection of IAV H5N1 among mammals are reported in farmed mink. Therefore, to discover antivirals against IAV, we screened a compound library by using the RNA‐dependent RNA polymerase (RdRp) assay system derived from H5N1 IAV including a drug‐resistant PA mutant (I38T) and a viral polymerase activity enhancing PB2 mutant (T271A). Upon screening, we found vidofludimus can be served as a potential inhibitor for IAV. Vidofludimus an orally active inhibitor for dihydroorotate dehydrogenase (DHODH), a key enzyme for the cellular de novo pyrimidine biosynthesis pathway. We found that vidofludimus exerted antiviral activity against wild‐type and drug‐resistant mutant IAV, with effective concentrations (EC50) of 2.10 and 2.11 μM, respectively. The anti‐IAV activity of vidofludimus was canceled by the treatment of uridine or cytidine through pyrimidine salvage synthesis pathway, or orotic acid through pyrimidine de novo synthesis pathway. This indicated that the main target of vidofludimus is DHODH in IAV RdRp expressing cells. We also produced recombinant seasonal IAV H1N1 virion and influenza B virus (IBV) RdRp assay system and confirmed vidofludimus also carried highly antiviral activity against seasonal IAV and IBV. Vidofludimus is a candidate drug for the future threat of IAV H5N1 infection among humans as well as seasonal influenza virus infection. [ABSTRACT FROM AUTHOR]

Isonicotinohydrazide is the first‐line medication in the prevention and treatment of tuberculosis. Antitubercular, antibacterial, antifungal, antiviral, anti‐inflammatory, antimalarial activity, anticancer, antineoplastic activity, and anti‐HIV activity are all demonstrated by drugs with a pyrimidine ring. The current study focuses on the synthesis of N‐(4‐(substituted‐phenyl)‐6‐(substituted‐aryl) pyrimidin‐2‐yl)‐2‐(2‐isonicotinoylhydrazinyl) acetamide from isonicotinohydrazide. Newly synthesized compounds were characterized by spectral studies (IR, 1H‐NMR, 13C‐NMR, and mass spectroscopy). They were screened for their antituberculosis, antimalarial, and antiprotozoal activities and compared with standard drugs. Molecular docking of isonicotinohydrazide‐bearing pyrimidine motifs was also done for some of the active compounds. [ABSTRACT FROM AUTHOR]

This study reports synthesizing and characterizing imidazolium‐based ionic liquids (ILs) using substituted benzoates as anions. Thermal stability of ILs described using thermogravimetric analysis (TGA). One inherent property of ILs is aggregates or cluster formation due to supramolecular interactions. The supramolecular interaction in synthesized ILs has been studied through Electrospray ionization mass spectrometry (ESI‐MS). The potential of ILs as organic catalysts is investigated in multicomponent reaction (MCR) using urea, malononitrile, and different aromatic aldehydes to prepare phenyl pyrimidines derivatives. The results demonstrate that catalysis with ILs effectively reduces reaction time and enhances yield. ILs entities are hypothesized to form new assemblies with reactive moieties of reactants through supramolecular interactions. The ILs can be reused and recycled. [ABSTRACT FROM AUTHOR]

The study focused on developing new triazolopyrimidine derivatives as potential DNA Gyrase inhibitors and antimicrobial agents. The compounds were designed, synthesized, and evaluated for their biological activities, safety, and ADMET properties. Encouragingly, the initial results showed promising potency and acceptable ADME parameters, forming a strong basis for further drug development research. The newly synthesized compounds were verified through spectra, mass, and elemental analysis. Notably, several compounds exhibited significant activity against both Gram‐positive and Gram‐negative bacteria, with MIC values ranging from 100 μg/ml to 250 μg/ml. importantly, the compounds were found to be safe, with no reported adverse effects or toxicities. Among the tested compounds, compound 2 m stood out as an excellent DNA Gyrase inhibitor, with an IC50 value of 0.89 μM, comparable to the reference drug ciprofloxacin with an IC50 value of 0.91 μM. Molecular docking studies confirmed that the compounds′ binding mode and docking scores were similar to ciprofloxacin, validating their antibacterial activity via DNA Gyrase inhibition. The research provides valuable insights into the potential of these newly synthesized triazolopyrimidine derivatives as DNA Gyrase inhibitors and antimicrobial agents. Their promising antibacterial activity and safe profile make them potential candidates for further development as antimicrobial agents. [ABSTRACT FROM AUTHOR]

Pyrimidine derivatives have attracted much attention in medicinal chemistry because of their diversified biological properties and potential therapeutic applications. The Suzuki‐Miyaura, Sonogashira, and Buchwald‐Hartwig coupling reactions provide flexible methods for synthesizing structurally diverse pyrimidine derivatives. These reactions can modify the pyrimidine structure to incorporate different functional groups and substitution patterns, improving the pharmacological activities and maximizing the drug‐like properties. Using other coupling partners, such as aryl and heteroaryl moieties, has produced novel pyrimidine‐based scaffolds with enhanced bioactivity profiles. This comprehensive review examines the biological activities of pyrimidine derivatives, concentrating on how their diversification via coupling reactions utilizing synthetic techniques has affected their pharmacological properties. Investigating various biological effects and exploring novel artificial techniques present great opportunities for creating next‐generation medicines with improved efficacy and selectivity. [ABSTRACT FROM AUTHOR]

A novel series of oxazolyl‐pyrimidine derivatives (11 a–j) have been synthesized and structures were confirmed by spectral data. The synthesized compounds were assessed for cytotoxic profile towards human cervix cancer (SiHa), lung cancer (A549), breast cancer (MCF‐7), and colon cancer (Colo‐205) cell lines by employing MTT assay and using etoposide as the positive control. The heteroaryl compounds having the terminal pyridyl (11 a) and thiazolyl (11 b) groups showed superior cytotoxic potency against cervix and lung cancer cell lines and varying methoxy substituted derivatives 11 c–11 e have excellent to good cytotoxic properties. Compound 11 a and 11 b have IC50 values in the range of 0.01±0.0034 to 0.17±0.059 μM and 0.10±0.038 to 0.66±0.077 μM respectively in the tested cell lines. The selected compounds 11 a and 11 b were studied by molecular docking to assess the binding interactions, binding energies, and possible mechanisms. The in‐silico ADME properties were calculated and all the compounds have the desired properties of drug‐like molecules. The toxicity results indicate that all the compounds are free from toxicity except 11 j, which has high tumorigenic properties. The optimized structure, energies of frontier molecular orbitals, molecular electrostatic potential, and NLO parameters for compound 11 a were determined using DFT/B3LYP level with a 6‐311++G(d,p) basis set. [ABSTRACT FROM AUTHOR]

Hot‐water‐soluble starch (HWSS) was employed as binder for fabrication of a composite from magnetite and Ag nanoparticles (NPs). Electron microscopy images showed a good dispersion of magnetite NPs in the matrix of HWSS. This observation indicates that HWSS tends to coat the maximum surface of magnetite by encapsulation of individual magnetite NPs, leading to disassembly of their aggregates. The HWSS‐coated magnetite NPs were employed as nano‐support for immobilization of fine Ag NPs generated in situ via reduction of Ag+ cations by glucose. Monitoring of the formation and growth of Ag NPs by UV–Vis spectroscopy made it possible to set up an optimal condition for fabrication of the nano‐composite and to verify the supremacy of HWSS‐coated magnetite NPs over bare magnetite NPs as support in this new protocol. Valuable insights into the texture of the nano‐composite were obtained by VSM, FT‐IR and XRD studies. The bio‐derived nano‐composite displayed an interesting magnetic property and an efficient catalytic activity in the three‐component synthesis of pyrano[2,3‐d]pyrimidines. It is a robust heterogeneous catalyst and can be simply retrieved from reaction mixtures by magnetic separation method. [ABSTRACT FROM AUTHOR]

The pyrido[2,3‐d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti‐inflammatory. Hence, we synthesized an efficient new series of 2‐thioxo‐pyrido[2,3‐d]pyrimidinone, 2‐hydrazinyl‐(quinolin‐2‐yl)pyrido[2,3‐d]pyrimidinone,N′‐(quinolin‐2‐yl)‐pyrido[2,3‐d]pyrimidine‐(formo/aceto)‐hydrazide and substituted‐(quinolin‐2‐yl)pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline‐pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design. [ABSTRACT FROM AUTHOR]

The δ isoform of class I PI3K (PI3Kδ) has been shown as a promising target for the treatment of hematologic malignancies and immune diseases. Herein, a series of pyrido[3,2‐d]pyrimidine derivatives were designed, synthesized and evaluated for the preliminary bioactivity. Compared with idelalisib, compound S5 exhibited excellent enzyme activity against PI3Kδ (IC50 = 2.82 nM) and strong antiproliferation activity against SU‐DHL‐6 cells (IC50 = 0.035 μM). Besides, S5 inhibited the phosphorylation of Akt, which is downstream of PI3Kδ, in concentration‐dependent manner. In view of the significant improvement in potency of PI3Kδ and selectivity over other PI3K isoforms, Compound S5 deserved further investigation as a promising PI3Kδ inhibitor. [ABSTRACT FROM AUTHOR]

An efficient, one pot, multicomponent, L‐arginine catalyzed synthesis of thiazolo[3,2‐a]pyrimidines is described. L‐arginine is an easily available, biodegradable, inexpensive, promising bio‐organic molecule. The current strategy is the first example of amino acid promoted, green synthesis of a series of thiazolo[3,2‐a]pyrimidines via the formation of CN and CC bonds. The major advantages of the present methodology such as recyclability of catalyst, operational simplicity, easy scale‐up, wide substrate scope, easy work‐up, inexpensive, excellent yields, and high atom economy make it a distinct improvement over the prevailing strategies. [ABSTRACT FROM AUTHOR]

We present a study on a new class of Schiff bases with pyrimidine linked hydrazinyl azole backbone. These compounds were synthesized using conventional and ultrasonication methods. Our design strategy incorporated three heteroaromatic azoles and various substituents on the pyrimidine scaffold to enhance antimicrobial properties. Antibacterial and antifungal screenings were conducted against specific pathogens, and molecular docking studies supported the results. The compounds exhibited significant antimicrobial activities, particularly against K. pneumoniae, surpassing the standard drug. These Schiff bases hold promise as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

The pyrido[1,2‐a]pyrimidine scaffold has great potential for the creation of bioactive substances. Here we propose a simple, cost‐effective, efficient approach to forming this core based on a one‐pot three‐component reaction of commercially available 3‐oxo esters, α,β‐unsaturated aldehydes and 1,3‐diaminopropane. The developed strategy makes it possible to obtain diverse pyrido[1,2‐a]pyrimidines thanks to alternative intramolecular cyclization pathways that depend on the substituent in the 3‐oxo ester. Their diastereomeric structure was determined using NMR spectroscopy and XRD. A mechanism for the formation of new pyrido[1,2‐a]pyridines has been proposed. [ABSTRACT FROM AUTHOR]

We report herein an unprecedented synthesis of difluoromethoxylated nitrogen‐containing heterocycles from the corresponding α‐(difluoromethoxy)ketones as versatile building blocks. Pyrazoles, isoxazoles and pyrimidines could be obtained via an enaminone intermediate, whereas in the direct reaction of α‐(difluoromethoxy)ketones with arylhydrazines, a Fischer indole synthesis was achieved. All these scaffolds, which are uncommon, or even sometimes novel, due to the directly attached emerging fluorinated group (EFG) −OCF2H, might be of high potential in life sciences and appear as an interesting alternative to more and more controversial classical fluorinated groups, such as the ubiquitous trifluoromethyl group. [ABSTRACT FROM AUTHOR]

Brønsted acid‐mediated intramolecular cyclization of 2‐amidoazulene derivatives, prepared by the reaction of 1‐cyano‐2‐aminoazulene derivatives with perfluoroalkyl acid anhydrides, resulted in the formation of 2‐perfluoroalkylazuleno[2,1‐d]pyrimidin‐4(3H)‐ones. Heating of these products in phosphoryl chloride led to 4‐chloro‐2‐perfluoroalkylazuleno[2,1‐d]pyrimidines. We also evaluated the reactivity of these pyrimidin‐4(3H)‐ones and pyrimidine derivatives toward the electrophilic and nucleophilic substitution reactions, revealing that a variety of functional groups can be incorporated into these derivatives. The NMR studies, NICS calculations, and single‐crystal X‐ray structure analyses revealed structural features including the bond‐length alternation of the azuleno[2,1‐d]pyrimidin‐4(3H)‐ones and pyrimidine derivatives. [ABSTRACT FROM AUTHOR]

Pyrimidine annulated five‐membered heterocyclic scaffolds containing oxygen as furopyrimidine, particularly furo[2,3‐d]pyrimidine derivatives are an important class of heterocyclic compounds in pharmaceutical discovery research. Furo[2,3‐d]pyrimidines are generally synthesized either from a pyrimidine derivative by constructing a furan ring on the parent pyrimidine ring or from a suitably functionalized furan ring by generating the pyrimidine ring on the parent furan ring. Moreover, there is a wide range of multicomponent reactions that include barbituric acids as starting material for the synthesis of these compounds. Also, the reaction of barbituric acids with alkenes, alkynes, aldehydes, ketones, ninhydrin, and chloroacetylchloride, and Cloke–Wilson rearrangement of spirocyclopropyl barbiturates afforded furo[2,3‐d]pyrimidine derivatives. This review is an attempt to compile the literature of various synthetic procedures toward barbituric acids‐based furo[2,3‐d]pyrimidine and spirofuro[2,3‐d]pyrimidines. [ABSTRACT FROM AUTHOR]