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• W4286374675 abstract "Introduction. Compounds with a hydroxypyrimidine fragment in their structure exhibit pronounced and diverse biological activity. The low solubility of many hydroxypyrimidine derivatives in water is a significant drawback in the development of new medicines. From 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one, its water-soluble form being a sodium salt was obtained. This compound, as it was revealed during the computer screening of its possible biological acti¬vity in silico, can potentially be used as a pharmaceutical substance for the production (manufacture) of drugs. Since the line of hydroxypyrimidine drugs in the topical dosage forms is extremely limited, and the resulting compound has hydrophilic properties, it is important to enclose the substance in a gel dosage form. Aim. Synthesis of a water-soluble form of new hydroxypyrimidine derivative, determination of its acute toxicity and anti-inflammatory activity, as well as critical stages of development and further production of a topical hydrophilic dosage form based on the obtained compound. Materials and Methods. The target compound was obtained from the interaction of 5-butyl-6-hydroxy-2,3-diphenylpyrimidin-4(3H)-one and an equimolar amount of an aqueous solution of sodium hydroxide. Acute toxicity was determined on white mice (5 groups of 10 animals, which were injected with a solution of the study compound at a dose of 1100, 1200, 1300, 1400, and 1500 mg/kg respectively), observing the development of the main symptoms and recording the time of death of the animals within 72 h from the moment of the drug administration. For the experimental assessment of anti-inflammatory activity, two models were used: formalin-induced mice paw edema and cotton pellet implantation-induced granuloma in rats (for each model there were 3 groups with 10 animals per group: the 1st group received the reference drug diclofenac, the 2nd – the compound under study, the 3rd (control) – sodium chloride solution). Results. The yield of the obtained sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidine-4-olate was 85 ± 1%. It has been proven in vivo that the test compound belongs to the 5th class of toxicity (practically non-toxic) and has a pronounced anti-inflammatory activity. An Ishikawa diagram was drawn up to determine the critical stages of the development and manufacture of a semisolid dosage form, a gel with a target substance. Conclusion. A new compound with anti-inflammatory action has been synthesized, sodium 5-butyl-1,2-diphenyl-6-oxo-1,6-dihydropyrimidin-4-olate, which has low toxicity and pronounced anti-inflammatory activity. The critical stages in the development and manufacture of a gel with synthesized compound are: preparation of the base and drug substance, introduction of the drug substance into the base, homogenization and packaging." @default.
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• W4286374675 date "2022-01-01" @default.
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• W4286374675 title "Synthesis and determination of the activity of a new derivative of hydroxyoxopyrimidine, a potential object for the manufacture of anti-inflammatory gel" @default.
• W4286374675 doi "https://doi.org/10.31549/2542-1174-2022-6-1-46-55" @default.
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