Current Organic Chemistry - Volume 28, Issue 20, 2024

The triazolopyrimidine scaffold indeed holds a prominent place in medicinal chemistry due to its versatile pharmacological properties. Researchers have explored the scaffold and its derivatives for various therapeutic applications. The unique structure of triazolopyrimidine has made it a valuable template for designing medicinally active molecules. The literature is full of studies showcasing the synthesis and biological activities of compounds containing the triazolopyrimidine ring, either fused or coupled with other heterocycles. The aim of this review is to provide a comprehensive and general summary of the recent advancements in the synthesis of triazolopyrimidine derivatives (Year 2021 to present).

Joint degeneration is a possible outcome of rheumatoid arthritis, an inflammatory disorder that is chronic, systemic, and progressive. Andrographis paniculata is known to contain many phytoconstituents that have demonstrated therapeutic effects in terms of inflammation. However, the therapeutic actions of Andrographis paniculata are still not fully understood. The present study aims to better understand rheumatoid arthritis and its possible treatments through the identification of relevant targets and mechanisms. A total of 47 common targets were identified for andrographolide, while 38 common targets were found for neoandrographolide. Additionally, 53 common targets were discovered for 5-hydroxy-7-methoxy flavone. Furthermore, a screening process was carried out to identify 9 primary hubb targets for andrographolide, neoandrographolide, and 5-hydroxy-7-methoxy flavone. Twenty useful gene ontology (GO) terms and twenty important Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways were found through the study of gene ontology and pathways. Molecular-docking analysis revealed that andrographolide had the highest binding efficacy (-7.8) towards the Serine/threonine-protein kinase 2 (PIM2) target. On the other hand, neoandrographolide displayed the highest binding efficacy towards mitogen-activated protein kinase (MAPK1) and Interlukine-6 (IL-6), with docking scores of (-9.0) and (-7.2), respectively. Furthermore, 5-hydroxy-7-methoxy flavone showed the highest docking score (-6.6) with Arachidonate 12-lipoxygenase (ALOX-12). The identification of numerous targets linked with various pathways in the treatment of Rheumatoid arthritis proves to be a helpful resource for future investigation into the mechanism and clinical applications of AP, NP, and 5H-flavone.

This study outlines the development of a novel approach utilizing microwave assistance for the alcohol dehydrogenative reaction. The process is catalyzed by manganese (II) and cobalt (II) in conjunction with chroman-4-one amino ligands. This research introduces a unique catalytic system capable of synthesizing various heterocyclic compounds, including pyrroles, pyridines, Betti bases, chromenes, and coumarins via alcohol dehydrogenation. The synthesis involved the preparation and characterization of a series of chroman-4-one amino ligands (C1-C6) using standard analytical techniques. These ligands, in combination with MnCl2‧4H2O and CoCl2, demonstrated remarkable catalytic activity, effectively driving alcohol dehydrogenation. The catalytic cycle was initiated by the in-situ formation of metal complexes with the ligands during the reaction. Characterization using ESI-MS confirmed the presence of metal complexes (Int-1) and other intermediates (Int-II and Int-III) throughout the catalytic cycle. Additionally, the controlled experiment corroborated the efficacy of the catalytic system, evidenced by the evolution of H2 gas.

A modified solid-liquid halex reaction was developed in the presence of a robust phase transfer catalyst under microwave conditions. A fast, mild, and practical microwave-assisted synthesis of 2,3-difluoro-5-chloropyridine 3 starting from 2,3,5-trichlorpyridine 1 and spray-dried KF in polar aprotic solvent was developed. The addition of Tetrakis (piperidino) phosphonium chloride as phase transfer catalyst A was studied under microwave irritation (450W) and increased the yield and significantly reduced the reaction time in contrast to the conventional heating procedure. The highest reaction rate was observed at 5 wt% phase transfer phosphonium salt catalyst to 2,3,5-trichloropyridine 1.

The synthesis of a series of multifunctionalized 4,5-diarylpyridazines via inverse electron-demand Diels-Alder reaction between highly oxygenated diarylacetylenes and unsubstituted 1,2,4,5-tetrazine was developed using polyalkoxybenzenes isolated from industrial essential oils as starting material. The reaction proceeded smoothly to afford combretastatin A-4 analogues with pyridazine linker in consistently high yield. In a phenotypic sea urchin embryo assay, diarylpyridazine with 3,4,5-trimethoxyphenyl and 3-amino-4-methoxyphenyl aryl rings was identified as a potent antimitotic microtubule-destabilizing compound.

^#Dedicated to the memory of our friend and colleague Dr. Dmitry V. Tsyganov (1963-2024).

We have created novel 1,2,3-triazole-based benzothiazinone derivatives in the current work. The produced compounds' in vitro antioxidant, antifungal, and antitubercular properties were assessed. Moreover, a simulated molecular docking analysis was conducted on the cytochrome P450 lanosterol 14α-demethylase active site to elucidate the enzyme's binding affinity and interactions with synthesised benzothiazinone derivatives. A notable correlation between these compounds' antifungal activity and binding score was indicated by molecular docking data. The synthetic 1,2,3-triazole-based benzothiazinone derivatives may satisfy the structural criteria for creating novel antifungal drugs, according to the results of the in vitro and in silico investigations.