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The starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC50 = 0.064 ± 0.0037 μg/ml and IC50 = 0.047 ± 0.0027 μg/ml, respectively, compared to the standard drug Larotrectinib with IC50 = 0.034 ± 0.0021 μg/ml for the HepG2 cancer cell line. In cell cycle analysis, compounds 7b, 15b, 16a and 16c caused the greatest arrest in cell cycle at the G2/M phase. In addition, compound 15b has a higher apoptosis-inducing effect (36.72%) than compounds 7b (34.70%), 16a (21.14) and 16c (26.54%). Compounds 7b, 16a and 16c were shown fit tightly into the active site of the TrKA kinase crystal structure (PDB: 5H3Q). Also, ADME study was performed on some selected potent anticancer compounds described in this study. Highlights: A series of new pyrido[4ʹ,3ʹ:3,4]pyrazolo[1,5-a]pyrimidine derivatives were synthesized. The anticancer activity of the new compounds were tested in vitro. Compounds 7b and 16c showed broad spectrum potent anticancer activity. Compound 15b induced cell cycle arrest at G2/M phase in HepG-2 cell line. Compound 7c, the most promising agent, can be absorbed very easily by the gastrointestinal tract with potential BBB permeability. [ABSTRACT FROM AUTHOR]

–Objective: In this paper, a series of piperazine pyrimidines and morpholine pyrimidines have been synthesized effectively, and their biological activities have been evaluated. Methods: We examined the cytotoxicity tests of the compounds against two human tumor cells (HCT-116, HeLa), as well as one human normal cells (L02), in order to determine their anticancer activity. Results: The compound (IV) outperformed the others, and flow cytometry was used to further examine how it works against cancer. Additionally, the (IV) molecule showed strong anticancer efficacy but was marginally less effective in apoptosis assays than the control 5-FU. Discussion: The compound (IV) chemical treated HCT-116 cells and HeLa cells in the cell cycle research had a larger percentage of cells in the G1 phase. The induction of apoptosis by interfering with the cell cycle may be the anticancer mechanism of this substance. Additionally, molecular docking investigated potential interactions between the substances and the Topo II active site. Conclusions: The groundwork for the creation and structural modification of new pyrimidine medications is laid out in this study. [ABSTRACT FROM AUTHOR]

Objective: To synthesize new dihydropyrazolo[1,5-a]pyrimidine derivatives and screen for the antibacterial and antifungal screening. Methods: We have synthesized a new series of 7-(1,3-diphenyl-1-H-pyrazol4-yl)-2-(methylthio)-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile compounds and screened compounds for antibacterial and antifungal activity. Gram-positive (Bacillus megaterium, Micrococcus spp.) and Gram-negative bacteria were tested for antibacterial activity (E.coli, S. typhi). Antifungal activity was tested on Ganoderma spp., A. niger, A. flavus, and Penicillium spp.Results: Some compounds have shown significant antimicrobial activity. Discussion: As per the results the compound possesses good biological activity due to presence of core pyrazolo[1,5-a]pyrimidine moiety. Conclusions: The synthesis of new 7-(1,3-diphenyl-1-Hpyrazol-4-yl)-2-(methylthio)-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarbonitrile compounds was successfully completed and characterized by relevant techniques. Compounds are screened for the biological activities with moderate to good results. The MIC of the synthesized compound is compared to marketed available standard drugs. [ABSTRACT FROM AUTHOR]

Pyrimidine is a pharmacologically important moiety that exhibits diverse biological activities. This review reflects the growing significance of transition metal-catalyzed reactions for the synthesis of pyrimidines (with no discussion being made on the transition metal-catalyzed functionalization of pyrimidines). The effect of different catalysts on the selectivity/yields of pyrimidines and catalyst recyclability (wherever applicable) are described, together with attempts to illustrate the role of the catalyst through mechanisms. Although several methods have been researched for synthesizing this privileged scaffold, there has been a considerable push to expand transition metal-catalyzed, sustainable, efficient and selective synthetic strategies leading to pyrimidines. The aim of the authors with this update (2017–2023) is to drive the designing of new transition metal-mediated protocols for pyrimidine synthesis. [ABSTRACT FROM AUTHOR]

2-Aminobenzimidazoles react with acetylene in the KOBut/DMSO superbase system (80°C, 20 min) to give benzimidazo[1,2-a]imidazoles and benzimidazo[1,2-a]pyrimidines formed by the self-assembly of the starting compounds with two or three molecules of acetylene. Vinyl derivatives of 1,3-dihydro-2H-benz[d]imidazole-2-imine were also isolated. [ABSTRACT FROM AUTHOR]

A series of 4-(1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine derivatives have been depicted by one-pot three component synthesis. The synthesis involved the reaction of 4-hydroxy-2H-chromen-2-one with 1H-pyrazole-5-carbaldehydes and urea/thiourea. The reaction was conducted in the presence of L-proline as a catalyst and ethanol as the solvent. This approach exhibits notable benefits like high yields, environmental compatibility, an easy procedure, short reaction periods, and mild reaction conditions. The synthesized compounds were examined for their cytotoxicity potential in HeLa and MCF-7 cells. Among all, 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione showed promising activity with IC50 values 8.0 and 8.5 µM towards MCF-7 and HeLa cells, respectively. In addition, the docking studies revealed that 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione had a favorable binding energy of –9.4 kcal/mol in inhibiting the human Aldo-keto reductase 1C3. [ABSTRACT FROM AUTHOR]

A series of novel (Z)-N′-(1-(aryl)ethylidene)-6-cyano-5-imino-3-methyl-7-(methylthio)-5Hthiazolo[3,2-a]pyrimidine-2-carbohydrazide derivatives was synthesized. All the synthesized compounds were investigated for antimalarial efficacy against Plasmodium falciparum parasite. It was found that, of all tested compound with 4-Cl and 2,4-Cl substituents in aromatic ring exhibited an excellent activity. Molecular docking analysis of the significantly active compounds was performed using PfDHFR enzyme. Compound with 4-Cl substituent demonstrates a binding energy of –9.0 kcal/mol, while that with 2,4-Cl substituent exhibits a binding energy of –9.3 kcal/mol. An analysis of their physicochemical and pharmacokinetics properties related to ADMET was also carried out for all the synthesized molecules. [ABSTRACT FROM AUTHOR]

The exponential development of resistance to conventional chemical insecticides adds another important motive for the creation of novel insecticidal active agents. One of the keys to meeting this challenge is the exploration of novel classes of insecticidal molecules with different modes of action. Herein, a novel series of spiro pyrimidine derivatives was prepared using some green synthetic methodologies such as microwave irradiation, and sonication under ultrasound waves. Spiro pyrimidine aminonitrile 1 is a key starting material for the synthesis of targets 2–9 by reaction with different carbon electrophiles and nitrogen nucleophiles. The structures of all the newly synthesized compounds were approved using spectral data. The toxicological efficiency and biological impacts of the synthesized spiro pyrimidine derivatives were assessed against Culex pipiens L. larvae. The toxicity of synthesized compounds showed remarkable variations against the C. pipiens larvae. Where, 3, 4 and 2 were the most efficient compounds with LC50 values of 12.43, 16.29 and 21.73 µg/mL, respectively. While 1 was the least potent compound with an LC50 value of 95.18 µg/mL. As well, other compounds were arranged according to LC50 values as follows 5 > 7 > 6 > 9 > 8. In addition, 3 and 4 exhibited significant prolongation of the developmental duration and greatly inhibited adult emergence. Moreover, many morphological deformities were observed in all developmental stages. Furthermore, cytotoxicity of the most effective compounds was assessed against the normal human cells (WI-38) as non-target organisms, where compounds 2, 4 and 3 showed weak to non-toxic effects. The study of binding affinity and correlation between chemical structure and reactivity was carried out using molecular docking study and DFT calculations to investigate their mode of action. This study shed light on promising compounds with larvicidal activity and biological impacts on the C. pipiens life cycle. [ABSTRACT FROM AUTHOR]

New cytisine-thienopyrimidine hybrid molecules were synthesized by reacting cytisine with 4-chlorothieno [2,3-d]pyrimidines in the presence of Et3N. The solvent effect on the course of the reaction was studied. The structures of the obtained compounds were elucidated using IR, 1H and 13C NMR spectroscopy and TLC-MS spectrometry. X-ray crystal structure analyses of the synthesized compounds were performed. [ABSTRACT FROM AUTHOR]

In the present study a series of ethyl 4-(substituted)-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate and ethyl 4-(substituted)-8-methoxy-2-methyl-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carboxylate have been synthesized and evaluated for their preliminary antibacterial, antifungal, antimycobacterial, antioxidant and antimalarial activity. Among all the synthesized derivatives some of the compounds exists good biological activity which is similar to that of standard drugs. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment microbial, tubercular and malarial disease. [ABSTRACT FROM AUTHOR]

An efficient and facile protocol for the synthesis of pyrimidine, pyridine and pyrazole ring systems was reported, Reaction of isothiocyanate with enaminone to give pyrimidinthione 4, the reactions of pyrimidinthione 4 with several active species such as ethyliodide, benzaldehyde, p-anisidine, acetylacetone were studied, the reactions of isothiocyanate 1 with active species such as ethyl cyanoacetate to form thioamide then oxazine, thiourea togivethiosemicarbazide, hydrazine, and phenylhydrazine resulted in pyrimidines. Novel compounds were tested for biological activity against Gram+ bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram– bacteria (E. Coli and Klebsiella pneumonia) using Gentamycin as reference standard drug, Results showed novel compounds as potent antibacterial agents against all bacterial strains except (Klebsiella pneumonia bacteria). [ABSTRACT FROM AUTHOR]

Imidazo[1,2-a]pyrimidine derivatives are a class of biologically active parent nucleus structures containing both imidazole and pyrimidine rings, which are important intermediates for the synthesis of a variety of drugs. This class of structures has attracted a lot of attention of researchers, and more and more synthetic strategies have been developed and reported. Currently, the main synthetic strategies are one-pot multi-component methods, microwave radiation, ultrasonic irradiation and other auxiliary Knoevenagel condensation and Michael addition methods to obtain these compounds, with the aim of achieving high yields, low time consumption and environmental friendliness. This review comprehensively summarizes the various synthetic methods as well as mechanism recently reported for the construction of this remarkable backbone structure and further used for the development of new chemical synthesis strategies and drug development as it has a wide range of applications in medicinal chemistry. In order to provide some impetus to the research of synthetic methods for this structure. [ABSTRACT FROM AUTHOR]

A novel access to pyrrolo[3,4-d]pyrimidine scaffold via tandem Staudinger/intramolecular aza-Wittig reaction of 5-acyl-4-(1-azidoalkyl)-3,4-dihydropyrimidin-2(1H)-ones promoted by PPh3 was developed. Synthesis of the starting pyrimidinones involved the reaction of readily available N-[(2-azido-1-tosyl)alkyl]ureas with Na enolates of benzoylacetone or acetylacetone followed by acid-catalyzed dehydration of the resulting products without their isolation. [ABSTRACT FROM AUTHOR]

The present study deals with a highly efficient and regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines via multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile and β-diketones in presence of p-toluenesulphonic acid under solvent-free condition. The structure of the isolated products was established on the basis of NMR (1H, 13C, and 19F) and IR spectral data. The scope of the reaction was studied using various β-diketones viz., aliphatic, aromatic, heteroaromatic, and trifluoromethyl-β-diketones. The protocol has several advantages, such as mild conditions, atom economy, practical simplicity, shorter reaction times, and avoidance of multi-step procedures. Seventeen diversely substituted pyrazolo[1,5-a]pyrimidines were screened against two breast cancer cell lines, named MCF-7 and BT474, and two leukemia cell lines, named NALM-6 and SB-ALL, using the MTT cytotoxicity assay. Preliminary results reveal that compound 2-amino-5-(4-bromophenyl)-3-(4-methoxyphenylazo)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine was identified as the most effective compound against all the four cancer cell lines with 65-49% cell survival. An efficient regioselective synthesis of 7-aryl-5-methyl- and 5-aryl-7-trifluoromethyl-2-amino-3-(4′-arylazo)-pyrazolo[1,5-a]pyrimidines is developed using solvent-free sequential multicomponent reaction of hydrazine hydrate, 2-(arylhydrazono)malononitrile with unsymmetrical β-diketones. [ABSTRACT FROM AUTHOR]

Quinazoline derivatives, as an important category of heterocyclic compounds, have received much attention for the design and development of new drugs due to their various pharmacological properties. Besides, there is a great deal of evidence showing pyrimidine analogs as anticancer agents. Thus, in the present study, for the design of new target compounds with cytotoxic activity, we focused on various quinazolinone and pyrimidine hybrids. A new series of quinazoline-pyrimidine hybrid derivatives (6a-6n) have been designed and synthesized as novel antiproliferative agents. All the synthesized compounds characterized based on their IR, NMR and Mass spectroscopic data. Antiproliferative activities of the new compounds were evaluated against three human cancer cell lines (MCF-7, A549, SW-480). The compounds were found to have appropriate potential with IC50 values ranging from 2.3 ± 5.91 to 176.5 ± 0.7 μM against the tested cell lines. Compound 6n exerted the highest antiproliferative activity with IC50 values of 5.9 ± 1.69 μM, 2.3 ± 5.91 μM and 5.65 ± 2.33 μM against A549, SW-480 and MCF-7 respectively. The results indicated that 6n could induce apoptosis in A549 cell line in a dose dependent manner and arrest in the S phase of cell cycle. Docking studies were also done to investigate the detailed binding pattern of the synthesized compounds against EGFR. Furthermore, molecular dynamic simulation and binding free energy calculation have been done to rescore initial docking pose of the synthesized compounds using ensemble-based MMGB/PBSA free energy method. According to the results, free energy calculation confirmed biological activity of compounds and also, Arg 817 and Lys 721 residues had the pivotal role in the high potency of 6n. Finally, the drug likeness and in silico ADME study were also predicted. [ABSTRACT FROM AUTHOR]

Utilizing the Knoevenagel–Michael tandem cyclocondensation reaction of barbituric acid/1,3-dimethylbarbituric acid, malononitrile, and aryl aldehydes, a sustainable methodology for the photosynthesis of pyrano[2,3-d]pyrimidine scaffolds has been devised. The present study expounds on the development of a green radical synthetic approach toward this class of compounds. In this study, a novel halogenated dicyanobenzene-based photosensitizer was utilized in an aqueous solution, exposed to air at room temperature, and activated by a blue LED as a renewable energy source for the purpose of generating energy. The primary aim of this endeavor is to employ a recently developed, easily obtainable, and affordably priced halogenated cyanoarene-based donor–acceptor (D–A). The 3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]} photocatalyst, as a thermally activated delayed fluorescence (TADF), is capable of inducing single electron transfer (SET) upon irradiation with visible light, thereby offering a facile and efficient approach with a high degree of effectiveness, energy efficiency, and eco-friendliness. The aforementioned phenomenon facilitates the exploration of the temporal changes that have occurred in the interactions between the surroundings and chemical constituents. The present study aimed to investigate the turnover number (TON) and turnover frequency (TOF) for pyrano[2,3-d]pyrimidine scaffolds. Additionally, it has been demonstrated that gram-scale cyclization is a viable method for utilization in industrial applications. [ABSTRACT FROM AUTHOR]

The effective methods for obtaining Fe3O4/CeO2, Fe3O4(TEOS)CeO2 nanocomposites with cerium dioxide content from 38 to 82% and from 32 to 70%, respectively were developed, their morphological, structural and magnetic studies were carried out. Cerium dioxide and magnetite composites have a crystalline structure and ferromagnetic properties characteristic for magnetite with non-magnetic impurities. Thereby it can be easily separated from the reaction medium by means of a permanent magnet. The nanocomposites exhibit catalytic activity in cyclocondensation reactions: the interaction of chalcones with acetoacetic ester in an alkaline medium in the presence of the 1.6 wt % resulting nanocomposite leads to the formation of m-terphenyl derivatives in one-stage reaction, and in the condensation reaction with the formation of the 4,6-dimethyl-N-(4-methyl-3-nitrophenyl)pyrimidine-2-amine and 4,6-dimethyl-N-(2-methyl-5-nitrophenyl)pyrimidine-2-amine, the yield of the target product was increased to 52 and 96.8%, respectively. The resulting composites can be used repeatedly, providing sufficiently high yields of the target product. [ABSTRACT FROM AUTHOR]

We have designed and synthesized a new series of amide derivatives of thiazolo[5,4-d]pyrimidines (10a-j) and their structures were characterized by 1H NMR, 13C NMR and mass spectral data. Furthermore, all compounds were evaluated for in vitro cytotoxicity effects against four human cancer cell lines such as PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) by employing MTT assay. The cytotoxicity effects of the amide derivatives (10a-j) were compared with etoposide utilized as the positive control. Among them, five compounds 10a, 10b, 10c, 10h and 10j possessed significant cytotoxicity properties as compared with etoposide. [ABSTRACT FROM AUTHOR]

The quantum chemical simulation of complexes of the glycyl-L-glutamic acid anion and the - alanyl-L-tyrosine Ala-L-Tyr zwitterion with nucleic bases (uracyl and cytosine) is performed using the DFT/B97D method. The most energetically favorable configurations of the complexes are found. Changes in the peptide structure during the formation of the complexes are analyzed. It is shown that the complexes are stabilized by intermolecular hydrogen bonds. The stacking effect competing with the hydrogen bonding in the orientation of peptide ions in the complex is described. The topological analysis is carried out within which bond critical points and their parameters are studied and hydrogen bond energies are found in the complexes. [ABSTRACT FROM AUTHOR]

A series of fifteen 2-substituted-3-(4-(pyridin-2-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-2-yl)thiazolidin-4-one, was prepared and characterized using analytical techniques like FT-IR, NMR (1H and 13C), and mass spectrophotometry. On screening, the compounds for antibacterial and antifungal potential, the findings portrayed to be the potent inhibitor of bacterial and fungal strains. The cytotoxicity of the prepared molecules was checked against HepG2 cells to calculate the percent viable cells, which was observed to be in the range of 70–81% up to 100 µM. The molecular docking assay was performed to assess the binding modes, the extent of the H-bond, and binding affinities against the receptor glucosamine-6-phosphatase (GlcN-6P) and lanosterol 14-α-demethylase. The findings portrayed that TYR312, SER316, GLU396, LEU 448, SER303, GLY398, and SER401 were the only amino acids of GlcN-6P that formed the H-bond with the prepared molecules. Similarly, the residues GLC5, GLC6, GLC7, SER60, TYR63, THR104, ASP229, LEU230, SER249, SER251, THR485 were the only amino acids of lanosterol 14-α-demethylase) that formed H-bond with the prepared molecules. The binding affinities for both receptors were found to be in the range of –8.5 to –6.3 kcal/mole (GlcN-6P), and –8.4 to –6.8 kcal/mole (lanosterol 14-α-demethylase). [ABSTRACT FROM AUTHOR]

A novel heterocyclic compounds containing pyrimido[4,5-d]pyrimidine (IIIa–IIIb) and (IVa–IVb), pyrazolo[3,4-d]pyrimidine (Va'–Ve') and (VIa'–VIe'), and pyrimido[4,5-b]quinoline (VIIa'–VIIe') and (VIIIa'–VIIIe') were designed and synthesized from the starting materials, 5-(bis(methylthio)methylene)-1,3-diphenylpyrimidine-2,4,6(1H,3H,5H)-trione (IIa) and 5-(bis(methylthio)methylene)-1,3-diphenyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (IIb) as efficient α,α-ketene dithioacetals is reported. The synthetic approaches of these types of compounds will provide an innovative molecular framework to the designing of new active heterocyclic compounds. In our study, we also present optimization of the method for synthesis along with antimicrobial evaluation of these newly synthesized compounds as antibacterial agents against the bacterial strains, like E. coli, B. subtilis, S. aureus, and P. aeruginosa also as antifungal agents against B. cinerea, C. arachidicola, A. solani, G. zeae, S. sclerotiorum, and R. cerealis. Preliminary bioassay showed that most of them exhibited certain-to-excellent antibacterial and antifungal activity. Among all the evaluated compounds, it was found that the synthesized compounds (IVb) and (VIIIc') showed the outstanding antibacterial activity (100%) against the strains E coli and S. aureus respectively comparable to the standard drug Ciprofloxacin at the same concenteration while the others exhibited better antifungal activity at 100 µg/mL. The outstanding antifungal activity (>90%) comparable to the positive controls trifloxystrobin and azoxystrobin exhibited by (VIIIc') against B. cinerea, (IVb) and (Vc') against A. solani, (IVb) against S. sclerotiorum alongwith compounds (VIb'–VIc') against R. cerealis. The structures of all the new synthesized compounds were elucidated by elemental analysis, IR, 1H NMR, and 13C NMR. [ABSTRACT FROM AUTHOR]

Fluorescently labeled nucleotides that contain a zwitterionic indodicarbocyanine dye have been synthesized. The dye has been attached at the C5 position of the pyrimidine base through a trans-alkene spacer. The substrate efficiency of the labeled nucleotides has been tested in recombinase polymerase amplification (RPA). As a result of RPA, full-sized target products of the ebpS gene fragment of the causative agent of bacterial pneumonia (Staphylococcus aureus) have been formed with a high density of fluorescent label. [ABSTRACT FROM AUTHOR]

A novel series of heterocyclic compounds containing thiazolo[3,2-a]pyrimidine and pyrimido[5,4-d]thiazolo[3,2-a]pyrimidine analogues were designed and synthesized starting from α,α-ketene dithioacetals (I), and their structures were confirmed by elemental analysis, IR, 1H NMR, and 13C NMR. In our study, we also present optimization of the synthetic method along with a biological evaluation of these newly synthesized compounds as antioxidants and antifungal. Preliminary bioassay showed that most of them exhibited certain-to-excellent antioxidant and antifungal activity. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 µg/mL while the others exhibited better antifungalal activity at 100 µg/mL. Thiazolo[3,2-a]pyrimidines (IVa–IVb) and (IVc–IVd) showed higher than 80% inhibition activity against C. arachidicola and P. infestans respectively whereas the thiazolo[3,2-a]pyrimidines (VIc–VId) showed maximum activity against B. cinerea and C. arachidicola, as for the tested pyrimido[5,4-d]thiazolo[3,2-a]pyrimidines (IXc–IXd) against G. zeae, P. piricola, and P. sasakii. In particular, thiazolo[3,2-a]pyrimidines (IVc–IVd) exhibited outstanding activity (> 90%) against G. zeae. Among all the evaluated compounds, it was found that some showed significant antioxidant activity at 10 µg/mL and the maximum DPPH radical scavenging activity was observed with synthetic thiazolo[3,2-a]pyrimidines (VIIc–VIId) and pyrimido[5,4-d]thiazolo[3,2-a]pyrimidine (IXc–IXd), especially pyrimido[5,4-d]thiazolo[3,2-a]pyrimidine (IXc) which possessed the highest antioxidant activity in comparable to that of standard vitamin C at similar concentration. [ABSTRACT FROM AUTHOR]

Routes were proposed for the synthesis of new pyrimidine-derived polycyclic nitrogen heterocycles – 4-(1H-pyrazol-1-yl)-2-(pyridin- 2-yl)pyrimidines with various donor substituents, isomeric 2-(1H-pyrazol-1-yl)-4-(pyridin-2-yl)pyrimidines, 2-(pyrazin-2-yl)-4-(1Hpyrazol- 1-yl)pyrimidines, and 4-(1H-pyrazol-1-yl)-2-(pyrimidin-2-yl)pyrimidines – which are of interest as N,N,N-tridentate ligands for the synthesis of transition metal coordination compounds. Experimental and theoretical studies of the electronic structure of the resulting compounds were carried out. [ABSTRACT FROM AUTHOR]

A method was developed for the synthesis of new fused 3-alkyl-substituted derivatives of thieno[3,2-d]pyrimidin-4(3H)-ones based on 11-(2-furyl)-8,8-dimethyl-7,10-dihydro-8H-pyrano[3′′,4′′:5′,6′]pyrido[3′,2′:4,5]thieno[3,2-d]-pyrimidin-4(3H)-one via nucleophilic substitution in the pyrimidine ring. A series of fused 4-amino-substituted 11-furylthieno[3,2-d]pyrimidine derivatives was also synthesized from the corresponding 4-chloro derivative. [ABSTRACT FROM AUTHOR]

Substituted prop-2-en-1-ones were obtained by the condensation reaction of 1-biphenyl-4-yl-ethanone with aromatic aldehydes in the presence of sodium hydroxide in an aqueous ethanol solution. Subsequent cyclization of the latter with hydrazine hydrate, phenylhydrazine, and thiosemicarbazide in an acidic medium leads to the corresponding pyrazolines. The reaction of amidine hydrochlorides with chalcones in a KOH–ethanol system leads to 2,4,6-trisubstituted pyrimidines. The luminescent and antibacterial properties of the resulting systems were studied. [ABSTRACT FROM AUTHOR]

In the realm of chemistry, increased energy consumption as a result of population development and industrialisation necessitates the usage of renewable energy sources. Nonrenewable energy sources emit not only greenhouse gases but also other toxic pollutants that harm all living creatures. This clearly necessitates the employment of an ecologically acceptable and cost-effective renewable energy source by the researchers. The Knoevenagel-Michael cyclocondensation of aldehyde derivatives, malononitrile, and barbituric acid/1,3-dimethylbarbituric acid via a three-condensation domino reaction can be used to create pyrano[2,3-d]pyrimidine scaffolds. This study establishes solar energy as a novel renewable energy source for the synthesis of pyrano[2,3-d]pyrimidine scaffolds under catalyst-solvent-free conditions, with excellent yields, reaction time savings, and atom economy. This reaction was carried out on a range of substrates with the use of a renewable energy source (sunlight) and a relatively simple experimental setup. The reaction was extremely fast, and there was no need for a solvent or chromatographic purification. According to a multigram scale reaction of model substrates, this reaction might be scaled up without affecting the outcome. Furthermore, the approach's broad applicability was proved by its usage to synthesis real-world pharmaceutical molecules. [ABSTRACT FROM AUTHOR]

In the present study, synthesis of a variety of 5-bromo-4-methyl-2-substituted pyrimidines endowed with pyrazolyl substituent appended in C4 position (7a-f) is described. These products are generated via treatment of 5-bromo-4-hydrazineyl-6-methyl-2-substituted pyrimidines (6a–f) and vinamidinum salt of (E)-N-(3-(dimethylamino)-2-phenylallylidene)-N-methylmethanaminium perchlorate (5) in good to excellent yields. The inhibitory and hydrogen-atom donating abilities of the synthesized products (7a-f) were assessed against nine pathogens including six bacterial strains (both Gram-negative and Gram-positive), three fungal strains and DPPH free radicals. Notable antioxidant properties were not observed with the products. IC50 values were in the range of 107.49–929.16 μg ml−1. The inhibition zone diameters of products at 10 mg ml−1 concentrations were recorded in the range of 10.51–18.44 mm via disk diffusion method. 5-Bromo-4-methyl-6-pyrazolylpyrimidine (7e) containing 2-(4-methylpiperazin) substituent showed better antioxidant and antimicrobial effects than other products. It was effective on all the tested microbial strains except Staphylococcus epidermidis. All the synthesized pyrazolyl pyrimidines, especially (7e) can be used to disinfect the environment and treat infectious diseases. [ABSTRACT FROM AUTHOR]

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation. [ABSTRACT FROM AUTHOR]

The current study involves the design and synthesis of a newly synthesized pyrrolo[2,3-d]pyrimidine derivatives to contain chlorine atoms in positions 4 and 6 and trichloromethyl group in position 2 using microwave technique as a new and robust approach for preparation of this type of pyrrolo[2,3-d]pyrimidine derivatives. The chemical structure of the synthesized pyrrolo[2,3-d]pyrimidine derivatives 3–19 was well-characterized using spectral and elemental analyses as well as single-crystal X-ray diffraction. All compounds were tested in vitro against seven selected human cancer cell lines, namely, MCF7, A549, HCT116, PC3, HePG2, PACA2 and BJ1 using MTT assay. It was found that compounds 14a, 16b and 18b were the most active toward MCF7 with IC50 (1.7, 5.7, and 3.4 μg/ml, respectively) relative to doxorubicin (Dox.) (26.1 μg/ml). Additionally, compound 17 exerted promising cytotoxic effects against HePG2 and PACA2 with IC50 (8.7 and 6.4 μg/ml, respectively) relative to Dox. (21.6 and 28.3 μg/ml, respectively). The molecular docking study confirmed our ELISA result which showed the promising binding affinities of compounds 14a and 17 against Bcl2 anti-apoptotic protein. At the gene expression level, P53, BAX, DR4 and DR5 were up-regulated, while Bcl2, Il-8, and CDK4 were down-regulated in 14a, 14b and 18b treated MCF7 cells. At the protein level, compound 14b increased the activity of Caspase 8 and BAX (18.263 and 14.25 pg/ml) relative to Dox. (3.99 and 4.92 pg/ml, respectively), while the activity of Bcl2 was greatly decreased in 14a treated MCF7 (2.4 pg/ml) compared with Dox. (14.37 pg/ml). Compounds 14a and 14b caused cell cycle arrest at the G1/S phase in MCF7. Compounds 16b and 18b induced the apoptotic death of MCF7 cells. In addition, the percentage of fragmented DNA was increased significantly in 14a treated MCF7 cells. [ABSTRACT FROM AUTHOR]

Cancer, caused by the failure of the mechanism that controls cell growth and proliferation, is usually associated with severe health issues. Nowadays, chemotherapy still occupies an important place in clinical cancer treatment, but the multidrug resistance and low specificity of chemotherapeutics are the major obstacles that undermine effective cancer treatment. Pyrazole and pyrimidine/fused pyrimidine can be rewarded with significant anticancer activity and tampered with in a range of places whereby some of their derivatives have received approval to treat cancer. Notably, pyrazole-pyrimidine/fused pyrimidine hybrids, blending of pyrazole and pyrimidine/fused pyrimidine pharmacophores into in a new chemical entity, can act on different targets simultaneously in cancer cells and possess potent in vitro and in vivo activity against both drug-sensitive and drug-resistant cancers. Moreover, several pyrazole-pyrimidine/fused pyrimidine hybrids which are exemplified by ruxolitinib (pyrazole-pyrrolo[2,3-d]pyrimidine hybrid) have already applied in clinics for cancer therapy, demonstrating pyrazole-pyrimidine/fused pyrimidine hybrids are pharmacologically significant scaffolds for the exploration of novel anticancer agents. This review aims to shed light on the recent developments of pyrazole-pyrimidine/fused pyrimidine hybrids with anticancer potential, and their structure-activity relationships as well as mechanisms of action are also discussed, covering papers published from 2019 to present, to facilitate further rational design of more effective candidates. [ABSTRACT FROM AUTHOR]

Context: The design and synthesis of safe and highly active sulfonylurea herbicides is still a challenge. Therefore, following some principles of structure-activity relationship (SAR) of sulfonylurea herbicides, this work focuses on evaluating two sulfonylurea derivatives bearing electron-withdrawing substituents, namely, –(CO)OCH3 and –NO2 on the aryl group, on herbicidal activity. To understand the effects caused by the substituent groups, the molecular and electronic structures of the sulfonylureas were evaluated by density functional theory. Likewise, the crystalline supramolecular arrangements of both compounds were analyzed by Hirshfeld surface, QTAIM, and NBO, with the aim of verifying changes in intermolecular interactions caused by substituent groups. Finally, through a toxicophoric analysis, we were able to predict the interacting groups in their biological target, acetolactate synthase, and verify the interactions with the binding site. Methods: All theoretical calculations were conducted using the highly parameterized empirical exchange-correlation functional M06-2X accompanied by the diffuse and polarized basis set 6-311++G(d,p). The atomic coordinates were obtained directly from the crystalline structures, and from the energies of the frontier molecular orbitals (HOMO and LUMO), chemical descriptors were obtained that indicated the influence of the functional groups in the sulfonylureas on the reactivity of the molecules. The intermolecular interactions in the crystals were analyzed using the Hirshfeld, QTAIM, and NBO surfaces. Toxicophoric modeling was performed by the PharmaGist webserver and molecular docking calculations were performed by the GOLD 2022.1.0 software package so that the ligand was fitted to the binding site in a 10 Å sphere. For this, genetic algorithm parameters were used using the ChemPLP scoring function for docking and ASP for redocking. [ABSTRACT FROM AUTHOR]

In this study, MnCoFe2O4@ovalbumin nanoparticles were synthesized using MnCoFe2O4 MNPs and egg white nano-ovalbumin. The surface of MnCoFe2O4 MNPs was activated with trisodium citrate anhydrou to improve the fabrication of nano-ovalbumin on MCF MNPs. The structure of these nanoparticles was properly characterized by Fourier-transform infrared spectroscopy (FT-IR), Scanning electron microscope, X-ray powder diffraction, Energy-dispersive X-ray spectroscopy, Transmission electron microscopy, Thermogravimetric, and Vibrating sample magnetometer. The catalytic activity of the MnCoFe2O4@ovalbumin nanoparticles was evaluated for the synthesis of pyrimido[4,5-d]pyrimidine derivatives via multi-component reaction of aldehyde, barbituric acid, urea, or thiourea under solvent-free condition. The desired products were prepared using an environmentally friendly method. Short reaction time, high efficiency, and easy work-up are some advantages of this procedure. This heterogeneous nanocatalyst can be easily recovered by a magnetic field and used at least six times without considerable loss of its activity. Also, MCF@OVL MNPs exhibited a CO2 adsorption capacity about 9.35 mmol/g at 25 °C. [ABSTRACT FROM AUTHOR]

In this work, the surface of Fe3O4 nanoparticles was functionalized with the glycine, furfural, and cobalt (II) nitrate hexahydrate to synthesize a novel support nanocatalyst (Fe3O4@gly@Furfural@Co(NO3)2). The characteristics of the nanocatalyst were confirmed by various techniques, such as energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectrometer, EDX mapping, scanning electron microscopy, X-ray diffraction, thermal gravimetric/derivative thermal gravimetric, vibrating sample magnetometer, and TEM. Finally, the performance of the nanocatalyst was investigated for the one-pot multicomponent synthesis of benzo[b]pyran and pyrano[2,3-d] pyrimidine derivatives. The good–excellent yield of the products was achieved in a green solvent under mild conditions at short reaction time. In addition, the green heterogeneous catalyst has features, such as environmental friendliness, easy separation from the reaction mixture by an external magnet, high catalytic activity, and reusability up to 6 stages without significant reduction of its catalytic activity. [ABSTRACT FROM AUTHOR]

An efficient synthesis of new pyrazolo-, triazolo-, and thiazolopyrimidinyl-substituted derivatives of 1-phenylpyrazol-3-one on the basis of a product of the condensation of 4-acetylpyrazolone difluoroboron chelate with dimethylformamide dimethyl acetal has been developed. [ABSTRACT FROM AUTHOR]

Various approaches to the synthesis of 3-halopyrazolo[1,5-a]pyrimidines were studied. It is shown that the most effective strategy consists in the construction of the azoloazine core followed by halogenation with N-iodo- or N-bromosuccinimide. A series of 3-halopyrazolo[1,5-a]pyrimidines, which are bioisosteric analogs of natural purine nucleic bases and the drug Triazavirin®, were synthesized using this strategy. The obtained compounds are interesting as precursors of novel C-nucleosides, which can be synthesized by C-C-coupling with (pseudo)ribosides containing a keto group. [ABSTRACT FROM AUTHOR]

A series of homoisoflavonoids bearing 3-(het)arylcoumarin moiety were synthesized by cascade reaction of enaminones with 8-dimethyl- aminomethyl-7-hydroxy-3-(het)arylcoumarins. The further reaction of synthesized coumarin-isoflavone hybrids with bidentate nucleophiles led to the formation of substituted 7-hydroxy-8-(1H-pyrazol-4-ylmethyl)coumarins, 7-hydroxy-8-(isoxazol-4-ylmethyl)- coumarins, and 7-hydroxy-8-(pyrimidin-5-ylmethyl)coumarins. [ABSTRACT FROM AUTHOR]

Purpose: Fluoropyrimidines are anticancer drugs and can cause hyperammonemia both intravenously and orally. Renal dysfunction may interact with fluoropyrimidine to cause hyperammonemia. We performed quantitative analyses of hyperammonemia using a spontaneous report database to examine the frequency of intravenously and orally administered fluoropyrimidine, the reported frequency of fluoropyrimidine-related regimens, and fluoropyrimidine's interactions with chronic kidney disease (CKD). Methods: This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression. Results: Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3–37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3–6.6) for orally administered capecitabine, 1.9 (95% CI 0.87–4.3) for tegafur/uracil, and 2.2 (95% CI 1.5–3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09–1.16). Conclusion: Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases. [ABSTRACT FROM AUTHOR]

Novel hybrid molecules of thiazolopyrimidine 4a–j have been prepared starting from various thiazoles 3a–j. The reaction of thiazoles 3a–j with thiourea yielded hybrid molecules 4a–j in an excellent yield. These molecules were screened for their anticancer activities against human breast carcinoma cell line (MCF-7), human lung adenocarcinoma cell line (A549) and human cervical cancer cell line (HeLa) using MTT assay. Among all molecules, compounds 4g and 4f exhibited potent cytotoxic activity. Compound 4g with IC50 value of 3.1 ± 0.4 µM and IC50 value of 9.8 ± 0.4 µM against A549 and HeLa cell line, respectively. Compound 4f with IC50 value of 6.8 ± 0.7 µM against MCF-7 molecular docking study of all synthesized molecules 4a–j was performed on topoisomerase II using the AutoDock technique. All the synthesized thiazolopyrimidine hybrid molecules have been characterized and confirmed using spectroscopic techniques. [ABSTRACT FROM AUTHOR]

Purine-containing nucleotide second messengers regulate diverse cellular activities. Cyclic di-pyrimidines mediate anti-phage functions in bacteria; however, the synthesis mechanism remains elusive. Here, we determine the high-resolution structures of cyclic di-pyrimidine-synthesizing cGAS/DncV-like nucleotidyltransferases (CD-NTases) in clade E (CdnE) in its apo, substrate-, and intermediate-bound states. A conserved (R/Q)xW motif controlling the pyrimidine specificity of donor nucleotide is identified. Mutation of Trp or Arg from the (R/Q)xW motif to Ala rewires its specificity to purine nucleotides, producing mixed purine-pyrimidine cyclic dinucleotides (CDNs). Preferential binding of uracil over cytosine bases explains the product specificity of cyclic di-pyrimidine-synthesizing CdnE to cyclic di-UMP (cUU). Based on the intermediate-bound structures, a synthetic pathway for cUU containing a unique 2'3'-phosphodiester linkage through intermediate pppU[3'−5']pU is deduced. Our results provide a framework for pyrimidine selection and establish the importance of conserved residues at the C-terminal loop for the specificity determination of CD-NTases. Here, the authors present structural and functional characterization of bacterial CD-NTases that synthesize cyclic dipyrimidines for phage resistance, revealing a (R/Q)xW motif dictating pyrimidine selection which suggests a sequential pathway for synthesizing 2'3'-cyclic di-UMP. [ABSTRACT FROM AUTHOR]

Whether TMPRSS2-ERG fusion and TP53 gene alteration coordinately promote prostate cancer (PCa) remains unclear. Here we demonstrate that TMPRSS2-ERG fusion and TP53 mutation / deletion co-occur in PCa patient specimens and this co-occurrence accelerates prostatic oncogenesis. p53 gain-of-function (GOF) mutants are now shown to bind to a unique DNA sequence in the CTNNB1 gene promoter and transactivate its expression. ERG and β-Catenin co-occupy sites at pyrimidine synthesis gene (PSG) loci and promote PSG expression, pyrimidine synthesis and PCa growth. β-Catenin inhibition by small molecule inhibitors or oligonucleotide-based PROTAC suppresses TMPRSS2-ERG- and p53 mutant-positive PCa cell growth in vitro and in mice. Our study identifies a gene transactivation function of GOF mutant p53 and reveals β-Catenin as a transcriptional target gene of p53 GOF mutants and a driver and therapeutic target of TMPRSS2-ERG- and p53 GOF mutant-positive PCa. TP53 alteration and TMPRSS2-ERG fusion are often found together in prostate cancer. Here, the authors show that gain-of-function mutant p53 collaborates with ERG proto-oncogene to drive prostate cancer tumourigenesis by activating beta-catenin expression and afterwards pyrimidine synthesis. [ABSTRACT FROM AUTHOR]

In this work, the surface of Fe3O4 nanoparticles was functionalized with the glycine, furfural, and cobalt (II) nitrate hexahydrate to synthesize a novel support nanocatalyst (Fe3O4@gly@Furfural@Co(NO3)2). The characteristics of the nanocatalyst were confirmed by various techniques, such as energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectrometer, EDX mapping, scanning electron microscopy, X-ray diffraction, thermal gravimetric/derivative thermal gravimetric, vibrating sample magnetometer, and TEM. Finally, the performance of the nanocatalyst was investigated for the one-pot multicomponent synthesis of benzo[b]pyran and pyrano[2,3-d] pyrimidine derivatives. The good–excellent yield of the products was achieved in a green solvent under mild conditions at short reaction time. In addition, the green heterogeneous catalyst has features, such as environmental friendliness, easy separation from the reaction mixture by an external magnet, high catalytic activity, and reusability up to 6 stages without significant reduction of its catalytic activity. [ABSTRACT FROM AUTHOR]

One-pot efficient copper-catalyzed approach for the synthesis of tetracyclic chromeno[4',3':4,5]pyrimido[1,2-b]indazolone and chromeno[4,3-d]-[1,2,4]triazolo[4,3-a]pyrimidine derivatives as a class of pharmacologically interesting compounds through the intramolecular domino condensation–aza-Diels–Alder reaction of aminoazoles and o-propargylated salicylaldehydes under reflux conditions has been described. [ABSTRACT FROM AUTHOR]

Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing. [ABSTRACT FROM AUTHOR]

Novel 1,3,4-oxadiazole-functionalized pyrido[2,3-d]pyrimidine derivatives were prepared starting from 2-amino-6-(thiophen-2-yl)-4-(trifluoromethyl)nicotinonitrile, which was reacted with trifluoroacetic acid in the presence of conc. H2SO4 and further with bromoethyl acetate to obtain ethyl 2-{4-oxo-7-(thiophen-2-yl)-2,5-bis(trifluoromethyl)pyrido[2,3-d]pyrimidin-3(4H)-yl}acetate. The reaction of the latter products with hydrazine hydrate gave 2-{4-oxo-7-(thiophen-2-yl)-2,5-bis(trifluoromethyl)pyrido[2,3-d]pyrimidin-3(4H)-yl}acetohydrazide. The subsequent treatment of the products with a series of aromatic acids resulted in the synthesis of 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]-7-(thiophen-2-yl)-2,5-bis(trifluoromethyl)pyrido[2,3-d]pyrimidin-4(3H)-ones and 2-aryl-5-({[7-(thiophen-2-yl)-2,5-bis(trifluoromethyl)pyrido[2,3-d]pyrimidin-4-yl]oxy}methyl)-1,3,4-oxadiazoles. All the synthesized final products were tested for anticancer activity against 4 human cancer cell lines: such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-Prostate cancer (HTB-81), and HeLa-Cervical cancer (CCL-2). Some of the tested compounds showed promising anticancer activity. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of benzofuro[3,2-d]pyrimidines was developed based on the oxidation of 2-(5-bromo-3,4-dihydropyrimidin-4-yl)phenols followed by the intramolecular nucleophilic aromatic substitution reaction. [ABSTRACT FROM AUTHOR]

2-Amino-6-sulfanylidene-5,6-dihydropyrimidin-4(3H)-one (1) was subjected to reaction with urea and aromatic aldehydes in acidic medium to yield pyrimido[4,5-d]pyrimidines 5a and 5b through intermediate formation of 5-arylmethylidene derivative 3, followed by 1,4-addition and cyclization with elimination of hydrogen sulfide. The use of thiourea or guanidine instead of urea in the aforementioned process afforded pyrimido[4,5-d]pyrimidines 5c–5f. The condensation of 1 with thiourea gave [1,2,4]thiadiazolo[2,3-a]pyrimi-dine derivative 6. The reaction of 1 with benzaldehyde, followed by air oxidation, produced benzothiopyrano-pyrimidine 8, and condensation of the latter with urea or thiourea yielded [1,2,4]oxa(thia)diazolo[2,3-a]thio-chromeno[2,3-d]pyrimidinles. Bis-[1,2,4]triazolo[4,3-a]pyrimidines 12a and 12b were synthesized by the cyclocondensation of 1 with malonic and succinic acid dihydrazides. The newly synthesized fused pyrimidine derivatives were tested for their in vitro antiproliferative activity against two cell lines: human gastric carcinoma (BGC-823) and human lung cancer (A-549) in comparison to the NIH/3T3 murine fibroblast cell line. Some of these compounds, in particular 5a–5f, 6, 8, 10a, 10b, 12a, and 12b, proved to be the most effective against all cancer cell lines, with no impact on normal cells. Using the structure–activity relationships as a guide, the greater activity of compound 10b against A-549 cells (IC50 = 14.15±0.33 g/mL) was attributed to the presence of iminothiadiazolidine and thiopyran moieties. [ABSTRACT FROM AUTHOR]

Rapid identification of different amino acid responses is of great importance in the field of biomedicine. Through the combination of the drug intermediate pyrimidine with the fluorophore BODIPY, a new type of high-efficiency fluorescent probe for rapid identification of different amino acids was prepared. In terms of photophysical properties, the UV absorption and fluorescence emission of the mercapto groups were observed under the conditions of different hydroperoxide equivalents and different solvents, and the maximum values were in the range of 534–538 and 554–560 nm. When different amino acids were added, the UV absorption and fluorescence emission ranges were 538–540 and 560–564 nm. Finally, the identification sensitivity of amino acids with different equivalents under different oxidant conditions was quickly detected by fluorescence cuvette. Among them, the identification response to tyrosine was the most obvious. [ABSTRACT FROM AUTHOR]