Refernces
10.1002/jhet.5570230531
The study, titled "Synthesis of Some 7-Substituted-2,4,8(1H,3H,7H)pyrimido[5,4-d]pyrimidinetriones," focused on synthesizing 7-substituted pyrimido[5,4-d]pyrimidinetriones under mild conditions, using ethyl 5-ethoxymethyleneamino-orotate as a key starting material. This compound was derived from ethyl 5-aminoorotate, which was obtained by reducing ethyl 5-nitroorotate with sodium dithionite. The ethyl 5-ethoxymethyleneamino-orotate was then cyclized with various primary amines to introduce a range of substituents into the 7-position of the pyrimido[5,4-d]pyrimidinetrione ring system. The synthesized compounds were characterized by their structures, reaction yields, and analytical data, including elemental analysis and NMR spectroscopy. The study also described the methylation of the 7-benzyl derivative to produce 1,3-dimethyl and 1,3,7-trimethyl derivatives using trimethyl phosphate. The synthesized compounds are of interest as deaza-analogs of naturally occurring antibiotics, as "homopurines" related to xanthine and uric acid, and as intermediates in the synthesis of folate analogs.
10.1021/ol048649m
The study investigates the Mannich-type C-nucleosidation reactions of 2,6-(oxo or amino)-disubstituted 5,8-diaza-7,9-dicarba-purines, a family of nucleobase analogues that are isomeric to natural purine nucleobases like adenine and guanine. The researchers synthesized various purinoids (1-4) and their adenine analogue using different chemical methods. For instance, the guanine analogue (2) was synthesized from N-formyl-glycyl-guanidine and trichloroacetonitrile through a series of reactions including hydrolysis and cyclization. The isoguanine analogue (3) and xanthine analogue (4) were prepared from 5-aminoimidazole using different reagents and reaction conditions. The study found that all these purinoids can undergo Mannich-type C-nucleosidation reactions with cyclic iminium salts, such as pyrroline derivatives (12 and 15), under mild conditions to form C-nucleosides. These C-nucleosides are isosteric with conventional N-nucleosides of natural purines. The reactivity of the purinoids in these C-nucleosidation reactions varies, with the 2,6-diamino derivative (1) being the most reactive and the 2-deamino derivative (adenine analogue) being the least reactive. The study also explored the stability and configuration of the resulting nucleosides, as well as the potential tautomerism in the isoguanine analogue (3). The findings suggest that these purinoids could be useful in studying the chemical etiology of nucleic acid structure and have potential applications in informational chemistry, medicinal chemistry, and chemical biology.
10.1021/acs.jmedchem.0c02145
This research focuses on the development of new P2X7 antagonists to treat neuroinflammation associated with neurodegenerative diseases (NDDs). The study introduces a series of novel non-nucleotide purine derivatives designed to be blood-brain barrier (BBB)-permeable, with the goal of identifying potential therapeutic candidates for central nervous system (CNS) disorders. The compounds were synthesized by linking purine or xanthine cores to an aryl group through different short spacers. They were tested through various assays, including YO-PRO-1 uptake assays, intracellular calcium dynamics, two-electrode voltage-clamp recordings, and interleukin-1? release assays. The most potent and selective antagonist identified was compound 6 (ITH15004), which demonstrated significant P2X7 blockade, good BBB permeability, and selectivity for human P2X7 over rat P2X1, P2X2, and P2X4 receptors.
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