Search Results (3)

Pyridazin-3(2H)one-based molecules have always attracted the attention of medicinal chemists due to their different pharmacological properties. The incorporation of such nuclei in therapeutically active molecules either as monocyclic units or as fused bi- or tricyclic scaffolds results in a wide range of pharmacological effects such as anti-inflammatory, analgesic, anticancer, antimicrobial, antiviral, cardiovascular-protective, antiulcer, and many other useful pharmacological activities. In accordance with our consolidated experience gained over the years in the chemistry and biology of tricyclic pyridazin-3(2H)ones, this review summarizes SAR studies of such pyridazinone-based polycyclic compounds endowed with various biological and therapeutic properties. Full article

This paper presented the efficiency of different Pd-based catalytic systems in a series of SM reactions of 4,5-dibromo-2-methylpyridazin-3(2H)-one with ferroceneboronic acid, ferrocene-1,1′-diboronoc acid, and its bis-pinacol ester. In addition to the disubstituted product, these transformations afford substantial amounts of isomeric 4- and 5-ferrocenyl-2-methylpyridazin-3(2H)-ones, and a unique asymmetric bi-pyridazinone-bridged ferrocenophane with a screwed molecular architecture. The reactions of phenylboronic acid, conducted under the conditions, are proven to be the most reductive in the conversions of ferroceneboronic acid, and produce 2-methyl-4,5-diphenylpyridazin-3(2H)-one as single product, supporting our view about solvent-mediated hydrodehalogenations that are supposed to proceed via the assistance of the ferrocenyl group present in the reaction mixture, or attached to the bromo-pyridazinone scaffold, which is constructed in the first SM coupling of the heterocyclic precursor. A comparative DFT modelling study on the structures and possible transformations of relevant bromo-, ferrocene- and phenyl-containing carbopalladated intermediate pairs was carried out, providing reasonable mechanisms suitable to account for the apparently surprising regioselectivity of the alternative hydrodebromination processes, and for the formation of the ferrocenophane product. Supporting the results of DFT modelling studies, the implication of DMF as a hydrogen transfer agent in the hydrodebromination reactions is evidenced by deuterium labelling experiments using the solvent mixtures DMF-d₇–H₂O (4:1) and DMF–D₂O (4:1). The organometallic products display antiproliferative effects on human malignant cell lines. Full article

Over the last decades, pyridazine derivatives are considered “privileged structures” in medicinal chemistry, with special attention being given to pyridazinones derivatives, which were found to have a large range of biological activities, including anticancer. On the other hand, because of the huge difficulties in cancer treatment, there is an urgent need from the pharmaceutical industry for new anticancer drug candidates. As part of our ongoing efforts in searching for new biologically active entities with anticancer potential, we report here the design, synthesis, structure and in vitro anticancer activity of a new class of pyridazinones derivatives, namely bis-pyridazinones. The structures of the compounds were proven by elemental and spectral analysis: IR, LC-MS, 1H-NMR, 13C-NMR, two-dimensional experiments 2D-COSY, HMQC, and HMBC. A few of the compounds were accepted by the National Cancer Institute (USA) for anticancer screening and were evaluated for their in vitro cytotoxic activity against a panel of 60 human tumor cell lines, representing cancers of the brain, breast, colon, kidney, lung, ovary, prostate, as well as leukemia and melanoma. Three of the tested compounds have proven to be active against non-small cell lung cancer HOP 92 and NCI-H226, CNC cancer SNB-75, renal cancer A498 and UO-31, with a growth inhibition between 50–80 mM. Interestingly, one compound (unsubstituted bis-pyridazinones I) has a selective anticancer activity, being active only on non-small cell lung cancer HOP 92, with a growth inhibition of 51.45 mM. SAR correlation has been performed. Full article