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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]

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]